Unit 3 Week 16- Joint Pain

What is the neurovascular supply of the ankle joint?

*Blood Supply:* derived from malleolar branches of the fibular artery and the anterior and posterior tibial arteries *Nerve supply:* derived from the tibial nerve and the deep fibular nerve

What are the three classifications of joints?

*Fibrous Joints*: articulating bones are joined by fibrous tissue; Sutures of the cranium are an example *Cartilaginous Joints*: articulating bones are united by fibrocartilage or hyaline cartilage *Synovial Joints*: articulating bones are separated by the characteristic joint cavity (containing synovial fluid) but are joined by an articular fibrous capsule lined with synovial membrane

Key features of rheumatoid arthritis

*HLA-DR4* 30 minutes or more of stiffness in the morning Joint pain is more severe in the morning Continuous pain or worsening pain Symmetric arthritis (both hands and knees)

What does a synovial joint consist of?

*Hyaline cartilage:* covers the full weight-bearing surface, providing a smooth yet resilient surface *Joint capsule:* a cavity, made of accessory ligaments, with synovial fluid inside. This reinforces the synovial membrane. *Synovial membrane lining:* secretes synovial fluid and covers the synovial cavity. It reaches to the edges of the hyaline cartilage. *Accessory structures:* accessory ligaments ("intracapsular" and "extracapsular"); articular discs or menisci, which are pads of fibrous cartilage; muscles and tendons; and subsynovial fat.

Rheumatoid Arthritis Specific Cytokines

*IL-6* stimulates B cells to differentiate into plasma cells, which then produce RA auto-antibodies. Also mediates systemic effects of RA, including the development of *C-reactive protein (CRP)* *TNF-alpha* is a key mediator in RA contributing to both systemic effects and bone destruction. Its multiple effects include: -enhances the proliferation of T and Bcells, increases the expression of adhesion molecules on endothelium, which promotes movement of T cells into the synovium -promotes destruction of bone by increasing the number of osteoclasts and decreasing the number of osteoblasts at the site of inflammation *IL-1* induces the production of multiple enzymes resulting in the production of inflammatory mediators and stimulates the production of matrix metalloproteases, resulting in breakdown of connective tissue. IL-1 also inhibits the production of proteoglycans and type II collagen

What are enzymes used in degradation of articular cartilage?

*Matrix metalloproteinases (MMPs)* are metal-dependent enzymes that catalytically breakdown a number of substrates including collagen II in articular cartilage Examples: *collagenases, gelatinases, and stomelysins* MMP-3 has the ability to degrade proteoglycan, fibronectin, laminin, and non helical regions of collagen *Aggrecanases* breakdown aggrecan proteoglycan to release core protein fragments and keratin sulfate. They are considered the most important proteases and are considered *biomarkers for degradation of articular cartilage*

What is the blood supply of the hip joint?

*Medial and lateral circumflex femoral arteries* are branches of the deep femoral artery. *The medial branch supplies the most blood.* *Artery to the head of the femur* is a branch of the obturator artery. It enters the joint through the ligament of the head of the femur.

*Charcot's Joint*

*Neuropathic arthropathy joint disorder* is a noninflammatory joint disease. Joint damage is secondary to impaired joint innervation leading to inability to sense pain (i.e. loss of proprioception and deep sensation leading to recurrent trauma) Causes: Different underlying neurologic diseases tend to affect different joints Diabetes Mellitus Syringomyelia Tabes Dorsalis (neurosyphyllis)

Symptoms and treatment of Osteoarthritis

*Symptoms:* Pain is the most common complaint Enlargement of distal interphalangeal joints (DIPs) called Herberden nodes (osteophytes) Enlargement of proximal interphalangeal joints (PIPs) called Bouchard's nodes (osteophytes) *Treatment:* Heat, decrease weight bearing, range of motion exercise, analgesics (NSAIDs, acetaminophen), viscosupplementation with oral chondroitin sulphate and glucosamine

Components Synovium

*Synovial lining (intima)-* a surface layer of cells consisting mostly of macrophages and specialized fibroblasts *Sub-synovium (subintima)*- a connective tissue substratum which contains numerous lymphatic vessels draining liquid from the synovial cavity. A *superficial microvascular net*

*True or False: Articular cartilage in adults possesses neither a blood supply nor lymphatic drainage.*

*True* Articular cartilage is surrounded by the extracellular matrix Although the cells continue to produce new extracellular matrix throughout life, they are ineffective in responding to injury. Wounds that are limited to the cartilage itself, without penetration of the subchondral bone, stimulate only a slight reaction in the adjacent chondrocytes.

Patellar ligament

A continuation of the quadriceps femoris tendon distal to the patella. It attaches to the tibial tuberosity.

Bursae of the knee

A bursa is synovial fluid filled sac, found between moving structures in a joint with the aim of reducing wear and tear on those structures. There are four bursae found in the knee joint: *Suprapatella bursa* - This is an extension of the synovial cavity of the knee, located between the quadriceps femoris and the femur. *Prepatella bursa* - Found between the apex of the patella and the skin. *Infrapatella bursa* - Split into deep and superficial. The deep bursa lies between the tibia and the patella ligament. The superficial lies between the patella ligament and the skin. *Semimembranosus bursa* - Located posteriorly in the knee joint, between the semimembranosus muscle and the medial head of the gastrocnemius.

Fibrous Joint

A fibrous joint is the most simple joints where the bones are bound by a tough, fibrous tissue (fibrous ligaments). These are typically joints that require strength. Fibrous joints can be further sub-classified into sutures, gomphoses and syndesmoses.

Joint

A joint is defined as a connection between two bones in the skeletal system. Joints can be classified by the type of the tissue present (fibrous, cartilaginous or synovial), or by the degree of movement permitted (synarthrosis, amphiarthrosis or diarthrosis).

What is the basic definition of a joint?

A joint is is an articulation of junction between two or more rigid componets (bones, cartilage, or even parts of the same bone) Joints exhibit a variety of forms and functions Some joints have no movement, slight movement, and some are freely moveable

Components of the articular cartilage of joint tissue

A nonvascularized tissue consisting of *chondrocytes* and an ECM The *ECM* is a composite network of proteins, that is primarily collagens (*mainly collagen type II*) , interacting with polysaccharides and proteoglycans *Type II collagen* is the abundant collagen and *aggrecan* is the predominant proteoglycan (*core protein + glycosaminoglycan*(GAG)) Other non-collagenous important molecules in articular cartilage include *cartilage oligomeric matrix protein (COMP)* and *elastin* which provides elasticity to the joint

*Dislocation of the Proximal Tibiofibular Joint*

A rare and often missed diagnosis. It accounts for <1% of all knee injuries. The typical mechanism of injury is a fall onto an adducted and flexed knee. They can also occur as a result of high-energy trauma. Common clinical features include inability to weight-bear, lateral knee pain and tenderness/prominence of the fibular head. Complications of proximal tibiofibular joint dislocation include *common fibular nerve injury (the nerve winds around the neck of the fibula)*, and recurrent dislocation.

Synovial Joint

A synovial joint is defined by the presence of a fluid-filled joint cavity contained within a fibrous capsule. They are freely movable (diarthrosis) and are the most common type of joint found in the body. Examples include the knee, ankle, and hip Synovial joints can be sub-classified into several different types, depending on the shape of their articular surfaces and the movements permitted: Hinge, Saddle, Plane, Pivot, Condyloid, & Ball and Socket

*Rheumatoid Arthritis (RA)*

A systemic, chronic, inflammatory disease characterized by progressive arthritis, rheumatoid factor, and extra-articular manifestations. Females are affected 4x more frequently than men with the highest incidence at age 20-50 years. RA is thought to be caused by autoimmune reaction triggered by an infectious agent (e.g. EBV, parvovirus, human herpes virus 6) in a genetically susceptible individual Key physical symptoms include proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints are swollen on both hands B and T cells are activated leading to damage of synovial cells that express antigens that triggers B cells to produce rheumatoid factor (RF) RF is an IgM autoantibody that has specificity for the Fc portion pf IgG. RF and IgG join together to form immunocomplexes (Type III hypersensitivity). Immunocomplexes activate the compliment system to produce C5a, a chemotactic agent for neutrophils and other leukocytes to enter joint spaces. Chronic synovitis and pannus formation eventually occur Pannus is granulation tissue that is formed within the synovial tissue by fibroblasts and inflammatory cells. Pannus proliferates and releases cytokines (mainly TNF-alpha, IL-6, and IL-1) that eventually destroy the articular cartilage leading to fusion of the joint by scar tissue called ankylosis

*Pott's Fracture*

A type of ankle fracture that is characterized by a break in one or more malleoli. A Pott's fracture is a term used to describe a bimalleolar (medial and lateral malleoli) or trimalleolar (medial and lateral malleoli, and distal tibia) fracture. Also known as broken ankle, ankle fracture and malleolar fracture Occurs in combination with other injuries such as sprained ankle or other fractures of the foot, ankle or lower leg This type of injury is produced by *forced eversion of the foot.* It occurs in a series of stages: Forced eversion pulls on the medial ligaments, producing an avulsion fracture of the medial malleolus. The talus moves laterally, breaking off the lateral malleolus. The tibia is then forced anteriorly, shearing off the distal and posterior part against the talus.

*Anterior cruciate ligament injury*

ACL injury occurs when severe force anteriorly on the thigh or posteriorly on the leg can cause a tear of the ACL. This causes the tibia to be able to slide anteriorly from the femur, which is diagnostic as the "*anterior drawer sign*". Attempt to pull the tibia forwards, if it moves, the ligament has been torn. Skiing accidents are an example of a frequent cause of ACL tears. The anterior cruciate ligament (ACL) can be torn by hyperextension of the knee joint, or by the application of a large force to the back of the knee with the joint partly flexed.

Aggrecan

Aggrecan is also known as *cartilage-specific proteoglycan core protein (CSPCP)* or *chondroitin sulfate* (major GAG) *proteoglycan 1* Aggrecan has keratin sulfate (minor GAG) Aggrecan interacts with hyaluronan via link proteins forming large proteoglycan aggregates to resist compression forces with minimal deformation, and they also contribute to the water retention in articular cartilage

*Pseudogout*

Also known as *chondrocalcinosis,* is a term for the deposition of calcium pyrophosphate dehydrate crystals (shaped like rod or rhomboid) in knee joints, leading to inflammation In patients older than 50 years old Can present with fever and an increased WBC count and sedimentation rate Should raise suspicion about one of these metabolic diseases: Hypomagnesemia, hypophosphatemia, hemochromatosis, or hyperparathyroidism NSAIDs are the treatment of choice

Hinge Joint

Also known as *ginglymus* Permits movement in one plane - only *flexion and extension.* Movement around a single axis at right angles to the bone. These usually have strong collateral ligaments on each side reinforcing the joint. E.g. elbow joint, ankle joint, knee joint. *type of synovial joint*

Saddle Joint

Also known as *sellar* It is characterised by opposing articular surfaces with a reciprocal concave-convex shape. Movement in two basic axes, with circumduction E.g. carpometacarpal joints of the thumb *type of synovial joint*

Pivot Joint

Also known as *trochoid* Allows for *rotation only.* Rotary movement around a longitudinal axis. Rounded process of bone rotates within a sleeve or ring composed of a bony fossa and a strong ligamentous band E.g. proximal and distal radioulnar joints, atlantoaxial (atlas-axis) joint. *type of synovial joint*

*Ankle Sprain*

An ankle sprain refers to partial or complete tears in the ligaments of the ankle joint. It usually occurs via excessive inversion to a plantarflexed and weight-bearing foot. The lateral ligament is more likely to be damaged for two main reasons: The lateral ligament is weaker than the medial ligament or the lateral ligament resists inversion. *The anterior talofibular ligament is the lateral ligament most at risk of irreversible damage.* Damage or disruption of the soft tissue structures surrounding the ankle. Injury results from severe inversion or eversion of the ankle. Severe inversion injuries are much more common and result in damage to the lateral soft tissue structures. Patient presentation may range from mild pain and swelling to severe pain and swelling with an inability to walk. It is critical to realize that this presentation is the same for fracture of the distal fibula. Therefore, radiologic exam is necessary to rule out fracture and to direct clinical treatment. CT and/or MRI may be required to fully assess the extent of soft tissue damage

Rheumatoid Arthritis

An unknown synovial joint antigen causes IgM, IgG, and IgA antibodies (referred to as *rheumatoid factor (rf) anti-IgG*) to bind to the Fc region of *IgG*, resulting in a cascade of inflammatory responses. An angry mix of cells in the synovium (dendritic cells, macrophages, B cells, CD3+ T cells, PMN leukocytes and clumps of plasma cells) begin to release RF, leukotrienes, prostaglandins, and cytokines such as IL-1 and TNF-alpha. The attack results in erosion of joints, fibrin deposition, and cartilage replacement leading to fused joints. Type III and *Type IV* hypersensitivity

Articular cartilage

Articular cartilage is a firm rubbery tissue that covers the ends of bones. It provides a smooth gliding surface for joints and acts as a cushion between bones. Normal cartilage is smooth allowing easy gliding of the joint. When cartilage is injured, the smooth surface can become rough. Moving bones along a tough, damaged joint surface is difficult and causes pain. Damaged cartilage can also lead to arthritis in the joint. On occasion, the cartilage injury exposes the underlying bone.

Plane Joint

Articular surfaces that are relatively *flat*, allowing the bones to glide over one another. E.g. sternoclavicular joint, acromioclavicular joint, subtalar joint, joints of the tarsal bones of foot. *type of synovial joint*

Unhappy Triad

As the medial collateral ligament is attached to the medial menisicus, damage to either can affect both structure's functions. A lateral force to an extended knee, such as a rugby tackle, can rupture the medial collateral ligament, damaging the medial meniscus in the process. The ACL is also affected, which completes the 'unhappy triad'.

Synovial Joint Components

Bone attaches to an *articular cartilage,* a thin layer of hyaline cartilage that covers the entire articulating surface of each bone. It prevents friction between the bones at a synovial joint and *has no blood vessels* Articular cartilage on each bone is separated by *synovial fluid,* which is secreted by a thin *synovial membrane* lining the inner surface of the articular capsule *Synovial fluid is composed* of a dialysate of plasma that is a watery lubricant, viscous, elastic, and plastic maintaining articular cartilage cells and mainly immune system cells Synovial fluid provides cushioning & lubrication for the large forces placed on the joint Synovial joints provide free movement between bones they join. The ankle joint is considered a synovial joint

Biochemical composition of bones

Bone is a highly specialized form of connective tissue that makes up most of the skeleton and is the chief supporting tissue of the body Bone can simply be described as *inorganic material* deposited on an *organic matrix.* The inorganic material is largely *calcium phosphate* in the form of *hydroxyapatite crystals (Ca10(PO4)6(OH)2)* and contains carbonate (Mg & Na) The organic matrix of bone is called *osteoid.* *Type I collagen* is the primary constituent of osteoid comprising 95% and is linked together by cross linking molecules such as *pyridinoline (PYD) & deoxy-pyridinoline (DPD)* The remaining non-collagen portion (5%) of organic matter is referred to as *ground substance* and consists of a mixture of various *proteoglycans* (core protein + glycosaminoglycan or GAG) and other proteins some of which are specific for bone tissue (e.g. osteoclacin and bone sialoprotein)

Calcitonin

Calcitonin produced by the parafolicular cells of the thyroid gland *decreases both calcium and phosphate in blood plasma* by two mechanisms: *1.* Calcitonin inhibits activity of osteoclasts *2.* Calcitonin acts on renal tubules to decrease both calcium and phosphate reabsorption

*Transverse Avulsion Patellar Fracture*

Caused by indirect force generated by the quadriceps tendon. Transverse fractures of the patella are much more common than longitudinal or comminuted fractures. As with all patellar fractures, it is important to differentiate between fracture and bipartite or multipartite patella.

Condyloid Joint

Contains a convex surface which articulates with a concave elliptical cavity. They are also known as ellipsoid joints. Oval surfaces allowing movements in two planes at right angles to each other E.g. wrist joint, metacarpophalangeal joint, metatarsophalangeal joint. *type of synovial joint*

Damaged Cartilage

Damage to articular cartilage is a common problem: In a young individual, it disrupts the normal surface of the articular cartilage. As a result, *the cartilage that remains has less weight-bearing area* which causes the remaining cartilage to wear more rapidly. Furthermore, damage to a joint surface, particularly in a young person, can lead to premature arthritis.

What are the types of joints?

Fibrous Joint Cartilaginous Joint Synovial Joint

Diarthroses

Freely moveable joints

Gomphosis

Gomphoses are also immovable joints. They are found where the teeth articulate with their sockets in the maxilla (upper teeth) or the mandible (lower teeth). The tooth is bound into its socket by the strong periodontal ligament. *type of fibrous joint*

Iliofemoral ligament

Has a 'Y' shaped appearance, and prevents hyperextension of the hip joint during standing by screwing the femoral head into the acetabulum. It is the strongest of the four ligaments.

Treatment of Rheumatoid Arthritis

IL-6, TNF-alpha, and IL-1 release receptors that are targets for drugs prescribed for RA patients Drugs classified as DMARDs

What are the four ligaments of the hip joint?

Iliofemoral ligament Pubofemoral ligament Ischiofemoral ligament Ligament of the head of femur The four ligaments of the joint allow considerable flexion of the hip joint, but restrict extension of the joint to 10 to 20 degrees.

Synarthroses

Immovable joints

Cartilaginous Joint

In a cartilaginous joint, the bones are united by cartilage only, fibrocartilage or hyaline cartilage. There are two main types: synchondroses (primary cartilaginous) and symphyses (secondary cartilaginous). Avascular or anervous, except at their margins

Synchondroses Joint

In a synchondrosis, the bones are connected by hyaline cartilage. These joints are immovable (synarthrosis). An example of a synchondrosis is the joint between the diaphysis and epiphysis of a growing long bone, the epiphyseal plate (growth plate). *type of cartilaginous joint*

Pubofemoral ligament

It has a triangular shape, and prevents excessive abduction and extension.

Ligament of head of femur

It is a relatively small structure, which runs from the acetabular fossa to the fovea of the femur. It encloses a branch of the obturator artery (artery to head of femur), a minor source of arterial supply to the hip joint.

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*Medial meniscus injury*

Medial meniscus can be damaged independently by "twisting strains". (The lateral meniscus is hardly ever injured.) Small tears will heal themselves, but if the tear is large enough, the torn part of the meniscus can be removed with no loss of mobility. These injuries are especially common in football and volleyball.

*Osteoarthritis (OA)*

Most common form of arthritis with risk increasing with age OA is characterized by progressive degeneration of articular cartilage with no to minimal inflammation affecting weight-bearing joints Cytokines activate *matrix metalloproteinases* that cause degradation of proteoglycans and collagen type II IL-1 is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize MMPs. IL-1 also suppresses the synthesis of type II collagen and proteoglycans, and inhibits the transforming growth factor-beta stimulated chondrocyte proliferation Joint Findings: -Erosion and clefts in the articular cartilage with eburnation (exposed bone) and subchondral bone sclerosis (bone hardening that increases bone density) - Reactive bone outgrowths at the joint margins (osteophyte) - Joint mice (loose bodies): free floating fragments of cartilage and bone

*Femoral Neck Fracture*

Occur most commonly in the subcapital region. Associated with postmenopausal osteoporosis. Avascular necrosis of the femoral head is a complication that occurs in 10-30% of subcapital fractures secondary to disruption of the femoral circumflex arteries. Nonunion may occur.

What are the three principal cell types involved in bone formation and reabsorption?

Osteoblasts for osteoid synthesis Osteoclasts for bone reabsorption Osteocytes for bone remodeling

Parathyroid Hormone (PTH)

PTH is a hormone that *increases plasma calcium* by *increasing the number and activity of osteoclasts* (bone-resorbing cells) PTH acts on renal tubules to *reabsorb Ca2+ and excrete phosphate* in urine, thus increasing Ca2+ in blood plasma, but decreasing phosphate in blood plasma

*Patellar Fracture*

Patellar fractures can be caused by direct trauma such as a blow to the anterior aspect of the knee or may be due to indirect forces generated by the tension of the quadriceps tendon.

What are the major ligaments of the knee?

Patellar ligament Collateral ligaments Cruciate ligaments

*Posterior Hip Dislocation*

Posterior dislocation accounts for more than 90% of all hip dislocations. The femoral head is forced posteriorly, and tears through the inferior and posterior part of the joint capsule, where it is at its weakest. The most common mechanism for a posterior dislocation is with high-energy trauma, such as during an automobile accident when the knees impact the dashboard. The sciatic nerve runs posteriorly to the hip joint, in 10% of patients, the sciatic nerve is injured as a result. There are four radiographic features of a posterior hip dislocation: • Femoral head lateral and superior to the acetabulum. • Fracture of the posterior rim of the acetabulum in most cases. • Femur in internal rotation and adduction. • Affected femoral head may appear smaller secondary to magnification.

*Gout*

Primary gout arises from inborn errors of purine metabolism leading to hyperurecemia and deposition of *monosodium urate crystals that are needle shaped* in joints The primary cause of gout leading to over production of uric acid is deficiency of hypoxanthine-guanine phophoribosyl transferase (HGPRT) seen in patients with Lesch-Nyhan syndrome

Glycosaminoglycans (GAGs)

Repeating units of uronic acid or galactose and amino sugars *Hyaluronate:* glucosamine + glucuronate *Chondroitin sulfate:* galactosamine + glucuronate *Keratan Sulfate:* galactosamine + galactose

Biomarkers of bone formation

Serum levels of by-products of collagen biosynthesis (*N & C-peptides of type I collagen*) Serum levels of osteoblast-related proteins such as *alkaline phosphatase* and *osteoclacin (bone Gla protein)*

Amphiarthroses

Slightly movable joints

Ischiofemoral ligament

Spans between the body of the ischium and the greater trochanter of the femur, reinforcing the capsule posteriorly. It has a spiral orientation, and prevents hyperextension and holds the femoral head in the acetabulum.

Suture

Sutures are immovable joints (synarthrosis), and are only found between the flat, plate-like bones of the skull. There is limited movement until about 20 years of age, after which they become fixed and immobile. They are most important in birth, as at that stage the joints are not fused, allowing deformation of the skull as it passes through the birth canal. *type of fibrous joint*

Fibrous Joint examples

Sutures in the cranium Syndesmoses- the interosseous membrane joins forearm bones Gomphoses- the periodontist anchors the tooth in the socket

Symphyses Joint

Symphysial joints are where the bones are united by a layer of fibrocartilage. They are slightly movable (amphiarthrosis). A symphysis is a permanent cartilaginous union. They always have hyaline cartilage on the bony surfaces concerned, and these cartilaginous surfaces are joined by fibrous tissue or fibrocartilage. Examples include the pubic symphysis, and the joints between vertebral bodies. *type of cartilaginous joint*

Cartilaginous Joint examples

Synchondrosis- bones joined by epiphyseal plate (hyaline cartilage) Symphysis- the binding tissue is a fibrocartilaginous disc (intervertebral disc)

Syndesmosis

Syndesmoses are slightly movable joints (amphiarthroses). They are comprised of bones held together by an interosseous membrane. The tibia and fibula have an interosseous ligament or membrane, as do the radius and ulna. *type of fibrous joint*

What are the three general structure a synovial joint?

The *synovium* secretes the synovial fluid that provides nutrients required by tissue within the joint The *articular cartilage* is the thin layer of hydrated soft tissue that lines each articular bone end within the joint The *bone* is a rigid body tissue which is essentially inorganic mineral deposited on an organic matrix

*Posterior cruciate ligament injury*

The PCL ruptures when a player lands on the tibial tuberosity with the knee flexed. This is usually in conjunction with tibial or fibular collateral ligament tears. It is diagnosed with the "*posterior drawer sign*". This is where the clinician holds the knee in flexed position, and pushes the tibia posteriorly. If there is movement, the ligament has been torn. These injuries are pretty common in basketball, and can also happen in head-on collisions when seatbelts are not worn. The most common mechanism of posterior cruciate ligament (PCL) damage is the 'dashboard injury'. This occurs when the knee is flexed, and a large force is applied to the shins, pushing the tibia posteriorly. This is often seen in car accidents, where the knee hits the dashboard. The posterior cruciate ligament can also be torn by hyperextension of the knee joint, or by damage to the upper part of the tibial tuberosity.

Acetabular labrum

The acetabulum is a cup-like depression located on the inferolateral aspect of the pelvis. Its cavity is deepened by the presence of a fibrocartilaginous collar, *the acetabular labrum.* The head of femur is hemispherical, and fits completely into the concavity of the acetabulum.

*Ankle Joint*

The ankle joint (or talocrural joint) is a synovial joint located in the lower limb. It is formed by the bones of the leg (tibia and fibula) and the foot (talus). Functionally, it is a hinge type joint, permitting dorsiflexion and plantarflexion of the foot. The tibia and fibula are bound together by strong tibiofibular ligaments. Together, they form a bracket shaped socket, covered in hyaline cartilage. This socket is known as a *mortise.* The body of the talus fits snugly into the mortise formed by the bones of the leg. The articulating part of the talus is wedge shaped - it is broad anteriorly, and narrow posteriorly: *Dorsiflexion* - the anterior part of the talus is held in the mortise, and the joint is more stable. *Plantarflexion* - the posterior part of the talus is held in the mortise, and the joint is less stable.

What are the supporting structures of the proximal tibiofibular joint?

The articular surfaces of the proximal tibiofibular joint are lined with hyaline cartilage and contained within a joint capsule. The joint capsule receives additional support from: *Anterior and posterior superior tibiofibular ligaments* - span between the fibular head and lateral tibial condyle *Lateral collateral ligament* of the knee joint *Biceps femoris* - provides reinforcement as it inserts onto the fibular head.

What is the blood supply of the knee joint?

The blood supply to the knee joint is through the *genicular anastomoses* around the knee, which are supplied by the genicular branches of the femoral and popliteal arteries. *Genicular branches of femoral artery* contribute to genicular anastomosis *Popliteal branches, anterior recurrent, and posterior recurrent branches of the anterior tibial recurrent and circumflex fibular arteries* contribute to genicular anastomosis *Middle genicular branches of popliteal artery* penetrate the fibrous capsule of the knee joint and supply the cruciate ligaments, synovial membrane, and peripheral margins of the menisci

*Calcaneal fracture*

The calcaneus is often fractured in a *'crush' type injury.* The most common mechanism of damage is falling onto the heel from a height - the talus is driven into the calcaneus. The bone can break into several pieces, known as a *comminuted fracture.* Upon x-ray imaging, the calcaneus will appear shorter and wider. A calcaneal fracture can cause chronic problems, even after treatment. The subtalar joint is usually disrupted, causing the joint to become *arthritic*. The patient will experience pain upon inversion and eversion - which can make walking on uneven ground particularly painful.

*Distal tibiofibular joint*

The distal (inferior) tibiofibular joint consists of an articulation between the fibular notch of the distal tibia and the fibula. It is an example of a fibrous joint, where the joint surfaces are by bound by tough, fibrous tissue. The distal tibiofibular joint is supported by: *Interosseous membrane* - a fibrous structure spanning the length of the tibia and fibula. *Anterior and posterior inferior tibiofibular ligaments* *Inferior transverse tibiofibular ligament* - a continuation of the posterior inferior tibiofibular ligament. As it is a fibrous joint, the distal tibiofibular joint does not have a joint capsule (only synovial joints have a joint capsule).

*Hip Joint*

The hip joint is a ball and socket synovial joint, the femoral head is the ball, while the acetabulum is the socket. It is the second most movable joint in the body, with only the shoulder having greater range of motion. This joint is not only flexible, but strong by necessity. During standing, the entire weight of the body is transferred to the head and neck of the femur. The acetabular labrum helps provide this strength by grasping more than half of the head of the femur. The main ligaments of the hip joint are really thickenings of the fibrous capsule, which is attached to the acetabulum and transverse acetabular ligament. Some deep fibers pass circularly around the neck forming the *zona orbicularus*, forming a collar around the neck that constricts the capsule and helps hold the femoral head in the acetabulum.

What is the nerve supply of the hip joint?

The hip joint is innervated primarily by the sciatic, femoral and obturator nerves. These same nerves innervate the knee, which explains why pain can be referred to the knee from the hip and vice versa. *Anteriorly:* femoral nerve and branches; if present, accessory obturator nerve *Inferiorly:* obturator nerve, anterior division *Superiorly and posteriorly:* superior gluteal nerve *Posteriorly:* nerve to quadratus femoris

What are the articulating surfaces of the knee?

The knee joint consists of two articulations: *Tibiofemoral* - medial and lateral condyles of the femur articulating with the tibial condyles. The tibiofemoral joint is the weight-bearing joint of the knee. *Patellofemoral* - anterior aspect of the distal femur articulating with the patella. The patellofemoral joint allows the tendon of the quadriceps femoris (the main extensor of the knee) to be inserted directly over the knee, increasing the efficiency of the muscle. As the patella is both formed and resides within the quadriceps femoris tendon, it provides a fulcrum to increase power of the knee extensor, and serves as a stabilising structure that reduces frictional forces placed on femoral condyles. Both joint surfaces are lined with hyaline cartilage, and enclosed within a single joint cavity.

*Knee Joint*

The knee joint is a hinge type synovial joint, which mainly allows for flexion and extension (and a small degree of medial and lateral rotation). It is formed by articulations between the patella, femur and tibia. The knee joint is relatively weak and depends on several things to strengthen it. Its area of weight distribution is two or three times larger than either the tibia or the femur, which reduces the overall pressure. Consists of: menisci, bursar, ligaments, and articulating surfaces

Lateral ligament of the ankle

The lateral ligament originates from the lateral malleolus (a bony prominence projecting from the lateral aspect of the distal fibula). *It resists over-inversion of the foot*, and is comprised of three distinct and separate ligaments: *Anterior talofibular* - spans between the lateral malleolus and lateral aspect of the talus; *a flat, weak band* *Posterior talofibular* - spans between the lateral malleolus and the posterior aspect of the talus; *a thick, fairly strong band* *Calcaneofibular* - spans between the lateral malleolus and the calcaneus; *a round cord*

Menisci of the knee

The medial and lateral menisci are fibrocartilage structures in the knee that serve two functions: To deepen the articular surface of the tibia, thus increasing stability of the joint. To act as shock absorbers by increasing surface area to further dissipate forces. They are C shaped, and attached at both ends to the intercondylar area of the tibia. In addition to the intercondylar attachment, *the medial meniscus is fixed to the tibial collateral ligament and the joint capsule.* Damage to the tibial collateral ligament usually results in a medial meniscal tear. The lateral meniscus is smaller and does not have any extra attachments, rendering it fairly mobile.

Medial Ligament of the ankle

The medial ligament (or deltoid ligament) is attached to the medial malleolus (a bony prominence projecting from the medial aspect of the distal tibia). It consists of four ligaments, which fan out from the malleolus, attaching to the talus, calcaneus and navicular bones. The primary action of the medial ligament is to resist over-eversion of the foot. Stabilizes the ankle during eversion and prevents subluxation (partial dislocation) of the joint.

Osteoclacin

The most abundant non-collagenous protein in bone that is synthesized by osteoblasts Levels correlate with bone formation rate

Biomarkers of bone reabsorption

The most useful markers for bone reabsorption are collagen degradation products derived from enzymatic breakdown of collagen type I, particularly compounds in regions of cross-linking: *pyridinoline (PYD) & deoxy-pyridinoline (DPD) & n and c-terminal telopeptides (NTX and CTX)* Also non-collagenous matrix proteins such as *bone sialoprotein (BSP)* or osteoclast-specific enzymes like *tartrate-resistant acid phosphatase 5b or cathepsin K*

What is the nerve supply of the knee joint?

The nerve supply, according to Hilton's law, is by the nerves which supply the muscles which cross the joint. *These are the obturator, femoral, tibial and common fibular nerves.*

*Proximal tibiofibular joint*

The proximal and distal tibiofibular joints refer to two articulations between the tibia and fibula of the leg. These joints have minimal function in terms of movement but play a greater role in stability and weight-bearing. The proximal tibiofibular joint is formed by an articulation between the head of the fibula and the lateral condyle of the tibia. It is a plane type synovial joint; where the bones to glide over one another to create movement

*Subtalar Joint*

The subtalar joint is an articulation between two of the tarsal bones in the foot, *the talus and calcaneus.* The joint is classed structurally as a synovial joint, and functionally as *a plane synovial joint.* The subtalar joint is formed between two of the tarsal bones: Inferior surface of the body of the talus - *the posterior talar articular surface.* Superior surface of the calcaneus - *the posterior calcaneal articular facet.* As is typical for a synovial joint, these surfaces are covered by articular cartilage.

Synthesis of Vitamin D

The skin, liver, and the kidney are required for endogenous synthesis of active Vitamin D in response to hypocalcemia. The synthesis of vitamin D may be compromised in people living in cold, cloudy climates, patients with severe liver diseases, those with end-stage renal disease, Fanconi renal syndrome, and genetic deficiency in 1α-hydroxylase. In the liver, 25-hydroxylase acts on cholecalciferol (Vitamin D3) to produce 25-hydroxycholecalciferol. 25-hydroxycholecalciferol is acted on by 1α-hydroxylase in the kidney to produce 1,25-dihydroxycholecalciferol (*calcitriol*). α-hydroxylase is induced by PTH Calcitriol acts on duodenal epithelial cells as a lipid-soluble hormone by binding to an intracellular receptor. Its intracellular receptor then binds to enhancer sites of target genes and directly regulate transcription and translation of calcium-binding proteins which stimulate dietary calcium uptake from the GI tract. In the kidney, calcitriol stimulates calcium and phosphate reabsorption Calcitriol (and PTH) facilitates the absorption (release) of calcium and phosphate from bone stimulating osteoclasts. The actions of calcitriol in bones and the kidney help bring calcium levels back within the normal range

Stability of the Subtalar Joint

The subtalar joint is enclosed by a joint capsule, which is lined internally by synovial membrane and strengthened externally by a fibrous layer. The capsule is also supported by three ligaments: Posterior talocalcaneal ligament Medial talocalcaneal ligament Lateral talocalcaneal ligament An additional ligament, *the interosseous talocalcaneal ligament,* acts to bind the talus and calcaneus together. It lies within the *sinus tarsi* (a small cavity between the talus and calcaneus), and is particularly strong; providing the majority of the ligamentous stability to the joint.

What are the movements of the subtler joint?

The subtalar joint is formed on an oblique axis and is therefore the chief site within the foot for generation of *eversion and inversion movements.* This movement is produced by the muscles of the lateral compartment of the leg and tibialis anterior muscle respectively. The nature of the articulating surface means that the subtalar joint *has no role in plantar or dorsiflexion of the foot.*

What happens when there is an imbalance in joint tissue turnover?

The tissues in the joint (cartilage and bone) continuously remodel in a finely tuned balance between matrix synthesis and degradation. In common diseases like rheumatoid arthritis (RA) and osteoarthritis (OA), the normal balance is disturbed and shifted towards degradation in the established disease. This eventually leads to disruption of the structural and functional integrity of the joint. As a consequence of the disturbed matrix turnover, increased amounts of macromolecules or fragments thereof are released into synovial fluid and may subsequently reach the blood stream. Some fragments may also be found in the urine. This sequence of events forms the rationale for efforts to identify alterations in the tissue by quantifying matrix macromolecules, "molecular markers", in body fluids with the purpose to define non-invasive methods to monitor pathological tissue processes. Besides, OA and RA, other joint tissue diseases include noninflammatory neuropathic arthropathy joint disorder and inflammatory gouty arthritis

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The usual inflammatory wound-healing response is NOT observed in a damaged joint surface until the subchondral bone is penetrated. • Cells recruited from the marrow elements of the underlying bone attempt to fill the defect with new tissue. • The extent to which the new tissue resembles articular cartilage depends on the age and species of the host as well as the size and location of the defect. • Complete restoration of the hyaline articular cartilage and the subchondral bone to a normal status is rare. • NO treatment has been shown to be predictable in this regard.

Cruciate ligaments

These two ligaments connect the femur and the tibia. In doing so, they cross each other, hence the term 'cruciate' (Latin for like a cross) *Anterior cruciate ligament (ACL)*- it attaches at the anterior intercondylar region of the tibia where it *blends with the medial meniscus.* It ascends posteriorly to attach to the femur in the intercondylar fossa. *It prevents anterior dislocation of the tibia onto the femur.* *Posterior cruciate ligament (PCL)*- attaches at the posterior intercondylar region of the tibia, and ascends anteriorly to attach to the anteromedial femoral condyle. *It prevents posterior dislocation of the tibia onto the femur.*

*Tibial collateral ligament injury*

Tibial collateral ligament injury is caused by a blow to the lateral side of the knee. Since the tibial collateral ligament is firmly attached to the medial meniscus, tearing it frequently results in concomitant tearing of the meniscus. Furthermore, in many cases there is also trauma to the ACL, resulting in the "terrible triad", which is common in football. Injury to the collateral ligaments is the most common pathology affecting the knee joint. It is caused by a force being applied to the side of the knee when the foot is placed on the ground. Damage to the collateral ligaments can be assessed by asking the patient to medially rotate and laterally rotate the leg. Pain on medial rotation indicates damage to the medial ligament, pain on lateral rotation indicates damage to the lateral ligament. If the medial collateral ligament is damaged, it is more than likely that the medial meniscus is torn, due to their attachment.

Collagen synthesis

Tissue specificity of collagen crosslinking is governed primarily by the presence of either *Lysine or hydroxyLysine residues* in the oxidizable telopeptide (nonhelical) positions of collagen In skin and tendon, where no telopeptide hydroxylation occurs, the allysines (formed from telopeptide lysines via Lys oxidase rxn) react with Lys or OHLys in the helix to form aldimines (Schiff bases), whereas in cartilage & bone, the hydroxylysines in the telopeptides undergo similar rxns to initially form aldimines that are converted via Amadori rxns to more stable ketoamines. During maturation in the skin(tendon), the aldimines react with a helical histidine residue to produce a nonreducible, HHL (histidine-hydroxylysinonorleucine),or histidine dehydrohydroxymerodesmosine; whereas, in cartilage/bone the ketoimines react with allysines or hydroxyallysine to give rise to the pyridinium cross-links, PYD (pyridinoline) and DPD (deoxypyridinoline), and the corresponding pyrrole

Collateral ligaments

Two strap-like ligaments that act to stabilise the hinge motion of the knee, preventing excessive medial or lateral movement *Tibial (medial) collateral ligament* - A wide and flat ligament, found on the medial side of the joint. Proximally, it attaches to the medial epicondyle of the femur, distally it attaches to the medial condyle of the tibia. *Fibular (lateral) collateral ligament*- Thinner and rounder than the tibial collateral, this attaches proximally to the lateral epicondyle of the femur, distally it attaches to a depression on the lateral surface of the fibular head.

What is found in the ECM of the subintima?

Type I abd Type III collagen They carry unusual glycosylations at the hydroxylysine residues and hyaluroran as well as a fibronectin, laminin, entactin, and tenascin

Ball and Socket Joint

Where the ball-shaped surface of one rounded bone fits into the cup-like depression of another bone. It permits free movement in numerous axes. E.g. hip joint, shoulder joint. *type of synovial joint*