## Musculoskeletal & Rheumatology Muscle microstructure and contraction There are 3 types of muscle: smooth muscle , which is under involuntary control from the autonomic nervous system , cardiac muscle , which can contract autonomously but is under the influence of the autonomic nervous system and circulating chemicals , and skeletal muscles , which are under voluntary control from the somatic nervous system , usually attached to bones and contract to bring about movement . Smooth muscle is found in the walls of the airways. Flow chart Muscle fibers are arranged in different ways: parallel, fusiform, triangular, pennate (muscle fibers are placed at angles to the tendon) → unipennate, bipennate, and multipennate. The image depicts six different types of muscle fiber arrangements along with labeled diagrams of each type. The types shown are: 1. Parallel: Muscle fibers run parallel to each other. 2. Fusiform: Muscle fibers are spindle-shaped, wider in the middle and tapering at the ends. 3. Triangular: Muscle fibers spread out from a narrow point to a broad area. 4. Unipennate: Muscle fibers are arranged on one side of a central tendon. 5. Bipennate: Muscle fibers are arranged on both sides of a central tendon. 6. Multipennate: Muscle fibers are arranged around multiple tendons in a feather-like pattern. Table Muscle is made up of fascicles , which are made up of bundles of myofibers (muscle fibers), which are made up of many myofibrils , which are made up of many myofilaments . The different parts of muscles are surrounded by connective tissue. The entire muscle is surrounded by the epimysium , the fascicles are surrounded by the perimysium , and individual muscle fibers are surrounded by the endomysium . Logo The image is a labeled diagram illustrating the structure of skeletal muscle, showing the hierarchical organization from the whole muscle down to individual components. It includes: - Bone connected to the muscle via a tendon. - Muscle composed of bundles called fascicles. - Fascicles consisting of bundles of muscle fibers (myofibres). - Each myofibre contains myofibrils. - Myofibrils composed of smaller units called myofilaments. Flow chart Myofibers are covered by a plasma membrane called sarcolemma . There are deep channels that go down into the muscles called the transverse tubules or T-tubules . The cytoplasm of these fibers is called the sarcoplasm , which is where myoglobin and mitochondria are found. There is a network of fluid-filled tubules surrounding the myofibers called the sarcoplasmic reticulum ; these also store Ca 2+ . Myofibrils extend along the entire length of myofibers. The repeating unit of a myofibril is called a sarcomere (from one Z disc to another Z disc). Myofibrils are composed of 2 main protein types: actin and myosin . Dense protein Z discs separate sarcomeres. Inbetween 2 Z discs there are light bands and dark bands. The dark bands (A bands) are made up of thick myosin . The light bands (I bands) are made up of thin actin . Myosin and actin filaments overlap , but the degree to which they overlap changes during muscle contraction and relaxation. Between 2 Z discs, there is an M line which is dark but not as dark as a Z disc. Myosin is attached to this M line and it spreads out in both directions and comes into contact with the actin filaments, which are attached to the Z discs. It is the movement of acting over myosin that causes muscle contraction . The image illustrates the structural components of a myofibril in a muscle fiber. - On the left, a grayscale microscopic image shows the light (I band), dark (A band), and Z disc regions in a myofibril. - Below it, a colored schematic of a myofibril highlights the arrangement and labeling of the A band, I band, Z disc, M line, and H zone. - Further zoom-in diagrams show the molecular structure of the sarcomere, detailing the Z disc at the edges, the M line at the center, and the positioning of thick filaments (myosin) and thin filaments (actin) within the sarcomere. This diagram effectively visualizes muscle fiber's microscopic and molecular organization. Flow chart Myosin filaments are each made up of 2 globular heads and a single tail formed by 2 α -helices , which move and use ATP to make actin slide over the myosin filaments. Tails of several hundred molecules form one filament . Logo The image shows two illustrations of myosin, a motor protein. The top illustration depicts a long tail with two large heads at one end. The bottom illustration is a close-up view labeled "Myosin head," showing multiple myosin heads protruding along the length of a thick filament, emphasizing the structure of the heads and their arrangement. Flow chart Actin molecules are twisted into a helix . Each molecule has a myosin binding site where the myosin filament head binds to and pulls the actin along. The proteins troponin and tropomyosin are associated with actin; they move and uncover binding sites when calcium is present. The image depicts a segment of a muscle fiber showing the arrangement of key proteins involved in muscle contraction. It features a strand of actin (pink spherical units aligned in a chain) wrapped with tropomyosin (a purple strand). Attached to the tropomyosin are troponin complexes (small red and green units), highlighting their positions along the actin filament. Each component is labeled with blue tags: "Troponin complex," "Actin," and "Tropomyosin." This illustrates the molecular structure of the thin filament in muscle fibers. Flow chart During contraction, the I band becomes shorter while the A band remains the same length . The H zone narrowed or disappeared (space around M line where actin and myosin aren't yet overlapping). ## Initiation of muscle contraction: 1. Action potential opens voltage-gated Ca 2+ channels 2. Ca 2+ enters pre-synaptic terminal 3. Ca 2+ triggers exocytosis of vesicles 4. Acetylcholine diffuses across synaptic cleft 5. Ach binds to acetylcholine receptors and induces action potentials in the muscle 6. Local currents flow from depolarized region and adjacent region, causing the AP to spread along the surface of the muscle fiber membrane. 7. Ach is broken down by acetylcholine esterase in the synaptic cleft. The muscle fiber response to that molecule of Ach ceases . The action of Ach can be extended with the use of acetylcholine esterase inhibitors. ## Activation (in muscle fiber): 1. AP propagates along the surface membrane and into T-tubules 2. Dihydropyridine (DHP) receptors in the T-tubule membrane senses voltage change & changes the shape of the protein linked to the ryanodine receptor, opens the ryanodine 3. receptor Ca 2+ channel in the sarcoplasmic reticulum. Ca 2+ is released from the sarcoplasmic reticulum to the space around myofilaments. 3. Ca 2+ binds to troponin, causing tropomyosin to move out of the way and reveal the myosin binding site on the actin filaments. 4. Crossbridges attach to actin 5. Ca 2+ is actively transported into the sarcoplasmic reticulum while APs continue by an ATP-driven pump (uptake rate < or = release rate) Bar code Flow chart ## Excitation contraction coupling: 1. In the presence of Ca 2+ , there is movement of troponin from tropomyosin chain 2. This movement exposes myosin binding site on the surface of the actin chain 3. Charged myosin heads bind to the exposed site on the actin filament 4. This binding and discharge of ADP causes the myosin head to pivot ( power stroke ), pulling the actin filament to the center of the sarcomere (M line). 5. ATP binding releases the myosin head from the actin chain 6. ATP hydrolysis provides the energy to recharge the myosin head. A motor unit is a single motor neuron together with all the muscle fibers that it innervates. A single motor neuron can innervate many mu scle fibers but a motor fiber can't be innervated by more than one motor neuron. Stimulation of one motor unit causes contraction of all the muscle fibers it innervates . The image depicts the connection between the spinal cord and muscle fibers through motor neurons. The spinal cord is shown with a motor neuron cell body, which extends an axon forming part of the nerve. The nerve branches into two motor units (Motor unit 1 and Motor unit 2), each connecting to distinct groups of muscle fibers. The axonal terminals at the neuromuscular junctions interface with these muscle fibers. An enlarged view of the muscle fibers shows their detailed structure with branching axons connecting to the motor units, illustrating the neuromuscular junction where nerve signals trigger muscle contraction. Other Bar code Motor units can be slow or fast; fast can be fatigue resistant or fatigable. Slow motor units (S, type I) have the smallest cell bodies in diameter, small dendritic trees, thinnest axons, the slowest conduction velocity, and can maintain contraction levels for long periods of time. Fast, fatigue resistant motor units (FR, type IIA) have cell bodies with larger diameters, larger dendritic trees, thicker axons, faster conduction velocity, and can maintain contraction levels for long periods of time. Fast, fatigable motor units (FF, type IIB) have cell bodies with larger diameters, larger dendritic trees, thicker axons, faster conduction velocities, and can produce lots of force but can't maintain it for long. Different types of muscle fibers are randomly distributed throughout the muscle. Muscles have different proportions of slow and fast twitch muscles. Motor unit types are classified by the amount of tension generated, speed of contraction , and fatigability of the motor unit. The force that a single muscle can produce is regulated by 2 mechanisms simultaneously: recruitment and rate coding . Recruitment controls the number of motor units that are recruited in an order governed by the size principle : smaller units are recruited first . As more force is required, more units are recruited. This allows fine control under which low force levels are required. A motor unit can fire at a range of frequencies. With rate coding , slow units fire at a lower frequency. As the firing rate increases , the force produced by the unit increases . Summation occurs when units fire at a frequency too fast to allow the muscle to relax between arriving action potentials. Neurotrophic factors are a type of growth factor that prevents neuronal death and promotes growth of neurons after injury. Motor unit and fiber characteristics are dependent on the nerve that innervates them. If a fast and slow twitch muscle are cross innervated , the slow one becomes fast and vice-versa. The motor neuron has some effect on the properties of the muscle fiber it innervates. There are 3 main types of muscle contraction: isometric (muscle produces force but doesn't change its length), concentric (shortening of muscle length to produce movement), and eccentric (muscle is producing force but is lengthening → more force produced and can cause damage). Bar code The image illustrates three types of muscle contractions using an arm holding a dumbbell for demonstration: 1. Isometric: The muscle contracts with no movement in the arm. 2. Concentric: The muscle contracts and shortens, causing the arm to bend and lift the dumbbell upward. 3. Eccentric: The muscle contracts while lengthening, resulting in the arm extending downward with the dumbbell. Each type is labeled next to corresponding arm and muscle illustrations showing bone, muscle, and dumbbell positions. Arrows indicate movement for concentric and eccentric contractions. Flow chart Fiber types can change properties under many different conditions (plasticity); change from type IIB to IIA is the most common following training. Type I to II change is possible in cases of severe deconditioning or spinal cord injury . Microgravity during spaceflight results in a shift from slow to fast muscle fiber types. Aging is associated with loss of type I and II fibers but a preferential loss of type II fibers . This results in a larger proportion of type I fibers in aged muscle (evidence from slower contraction times ). ## Injury and healing The mechanisms of bone fracture are trauma -low energy or high energy, stress -abnormal or repetitive stresses on normal bone, or pathological -normal stresses on abnormal bone. Stress fractures happen due to overuse of bone where the stress exerted on the bone is greater than the bones' capacity to remodel, weakening the bone, a nd eventually causing a stress fracture and leaving the person at risk of a complete fracture. Stress fractures happen mainly to weight bearing bones (femur, tibia, metatarsals, navicular) and are usually activity-related (athñetes, occupational, military), for example, soldiers who have to carry 30-40kg while running several miles for many days. Stress fractures can also happen due to a combination of abnormal stresses and abnormal bone like in people with disordered eating (e.g. anorexia who eat very little but do a lot of exercise), amenorrhea, or osteoporosis. In pathological or insufficiency fractures the bone is insufficiently strong because of a pathology and a fracture happens because it isn't strong enough to sustain normal stresses. The underlying pathology can be local (e.g. osteomyelitis of a bone) or general (e.g. osteoporosis). The bone pathologies that can lead to a bone fracture include osteoporosis -soft bone, malignancy -primary or bone mets, vitamin D deficiency -osteomalacia or rickets, osteomyelitis, osteogenesis imperfecta, and Pagets. (pathological is usually used for infection and cancer while insufficiency is used for metabolic disorders like osteoporosis and vit. D deficiency; but all insufficiency are pathological). Insufficiency fractures happen, in the western world, usually because of osteopenia and osteoporosis (loss of bone density). It can be localized or generalized and primary or secondary. Primary osteoporosis is related to age (senile osteoporosis). Secondary osteoporosis can Bar code happen at any age and in any sex due to hormonal problems (e.g. hypogonadism), glucocorticoid excess, or alcoholism. People with osteoporosis will have fragility fractures (hip, spine, wrist) where low energy trauma that wouldn't normally cause a fracture will lead to a fracture. Insufficiency fractures can also happen due to vitamin D deficiency leads to demineralized, and hence, soft bone, predisposing the person to fractures. In a child, this presents as rickets, in an adult, it presents as osteomalacia. Another form of insufficiency can be congenital. People with osteogenesis imperfecta have decreased type I collagen, which decreases osteoid production, weakening the bones and potentiating insufficiency fractures. A metabolic disturbance of bone turnover that can also lead to insufficiency fractures is Paget's disease . Paget's disease causes either increased or decreased osteoblastic activity or increased or decreased osteoclastic activity. This causes disturbances in bone turnover, leading to bone deformities and pathological fractures. These patients, in chronic cases, can develop osteosarcomas. Pathological fractures can also be caused by malignancy . Bone cancers can be primary or secondary. Primary cancers arise from the bones themselves, and they can arise from osteoblastic tissue (osteosarcoma), chondral tissue (chondrosarcoma), and Ewing sarcoma and lymphoma can also cause primary bone cancers. Secondary is where you have metastatic bone tumors from other tissues (most common are cancers of the prostate, breast, kidney, thyroid, and lung). These metastases can lead to increased osteoblastic activity (prostate and breast cancers) or increased osteolytic activity (breast, kidney, thyroid, and lung cancers). ## Fractures are categorized by: - Soft tissue integrity - o Open fractures → Bone pokes out of skin - o Closed fractures → bone doesn't poke out through s kin, which is intact - Bony fragments - o Greenstick fractures → bone fragments are bent - o Simple fractures → 2 bone fragments with a fracture in between - o Multifragmentary (comminuted) fractures → many bone fragments - Movement - o Displaced → bone fragments moved apart a lot - o Undisplaced fractures → bone fragments haven't really moved Bar code The image provides a comparison of different types of bone fractures and their X-ray appearances. On the left side, six schematic diagrams show various fracture types in a leg bone: 1. Simple or Closed 2. Open 3. Transverse 4. Spiral 5. Impacted 6. Greenstick and Torus 7. Comminuted On the right side, a blue table is split into three columns labeled "Greenstick," "Simple," and "Multifragmentary (comminuted)." Below each label are X-ray images illustrating these fracture types: - "Greenstick" column shows two X-rays with partial fractures in long bones. - "Simple" column shows one X-ray with a clean, single fracture line. - "Multifragmentary (comminuted)" column shows an X-ray with multiple bone fragments. Flow chart In all tissues, healing occurs in the following process: bleeding → inflammation → proliferation (new tissue formation) → tissue remodeling In fracture healing, initially, you have blood and blood products, then you have inflammatory cells (neutrophils and macrophages), then you can either fibroblasts (collagen in tissues -ligaments or tendons), osteoblasts (bones), or chondroblasts (bones), finally macrophages, osteoclasts, and osteoblasts work together to remodel the tissues (bone or soft tissue). In bone healing, there is first bleeding in between the bone ends (hematoma), these blood products release cytokines, which bring cells to the fracture that produce granulation tissue and blood vessel formation. Then chondroblasts or osteoblasts secrete new bone tissue (initially soft callus -T2 collagen (cartilage), which is converted to hard callus -T1 collagen (bone-like)). After this repair phase, the hard callus responds to activity and the forces applied to it and functional demands and growth affect the way that this bone then grows out. This remodeling phase involves osteoblasts and osteoclasts. Wolff's Law: bone grows and remodels in response to the forces that are placed on it (both in fractures and growth). Bone healing can be primary or secondary. In primary bone healing , there is intramembranous healing (mesenchymal stem cell turns straight into an osteoblast) and you get a direct formation of woven bone . This happens in stable fractures where the ends are almost completely back together again from the fixation. In secondary bone healing , there is endochondral healing (mesenchymal stem cell turns into chondral precursor (cartilage), which then turns into an osteoblast) and more callus is produced than in primary healing (endochondral ossification). It involves responses in the periosteum and external soft tissues and relative stability . Bones heal at different rates. In general, upper limbs heal faster than lower limbs and hands heal faster than feet. Healing time varies according to age, biology, and comorbidities of the patient. Logo Fracture management involves reduction (bringing the fracture ends back together → closed/open), holding the fracture (holding those ends in the right position → metal/no metal), and once the bone healed, you need rehabilitation of the limb (the bone will be very stiff and may still be painful and weak → move, physiotherapy, use). To reduce fractures, you can pull on them ( closed reduction ), where you can manipulate the fracture or apply traction either via the skin or skeletal (pins in bone); or you can make a cut in the skin, going down to the fracture site and putting the bones back together ( open reduction ). Engineering drawing Skin traction: Skeletal traction: Engineering drawing Holding the fracture can be closed with plaster, traction, or open with fixation. In fixation , you can internally fix the fracture with metal under the skin, either intramedullary or extramedullary, or you can have pins sticking out to the skin ( external fixation ), which can be monoplanar or multiplanar. Photograph Internal extramedullary fixation: Other Closed holding, plaster: Internal intramedullary fixation: Screenshot from manual Photograph External monoplanar fixation: Photograph External multiplanar fixation: To rehabilitate the limb, the limb needs to be used (may need pain relief or retraining with physiotherapy) and moved, the muscles around the limb need to be strengthened, and in lower limbs, there needs to be weight bearing. Logo To decide how the fracture is managed, we first look at where is the fracture, then is the fracture displaced (have the bones moved apart), next, is it stable or is it at a joint surface, and finally, are the soft tissues ok, are there other illnesses, and what does the patient think. Tendonopathy can be caused by tendinosis (abnormal thickening of the tendon), tendinitis (inflammation of the tendon), rupture, or a combination of both. Ligament injuries have different grade classifications. In grade I, there is a slight incomplete tear with no notable joint instability; in grade II, there is a moderate/severe incomplete tear with some joint instability; in grade III there is complete tearing of 1 or more ligaments and there is obvious instability (surgery is usually required). Bar chart To manage tendon and ligament tears, you can immobilize so that the tendons and ligaments don't move through a plaster, boot, or brace and rely on the natural heal ing process, or you can surgically repair and suture the ligament or tendon. There are a lot of factors to consider when deciding to mobilize or immobilize a tendon/ligament. Immobilizing ligaments leads to less ligament laxity but less overall strength of scars while mobilization leads to scars that are wider stronger, and more elastic and to a better alignment/quality of collagen, however, some patients may be at higher risks in surgery Factors affecting tissue healing can be from the mechanical environment (movement and forces) or the biological environment (blood supply, immune function, infection, and nutrition). ## Bone and joint disorders Photograph Photograph ## Elderly fall fracture ## Case: - 78 yr old lady - Tripped and fell - Can't get up - Pain in right groin - Had a fall 1yr ago and sustained a wrist fracture - She had a right hip fracture that required fixation Causes of groin pain: Logo - Arthritis - Inguinal hernia (intestine) - Kidney stones - Appendicitis - Diverticulitis - Nerve impingement - Lymph nodes - Deformity of the lower limb (e.g. hip fracture) - Bursitis ## Risk factors of osteoporosis: - Age - Female, especially after menopause - Lifestyle - o Excess alcohol - o Smoking - o Physical inactivity - o Low body weight - Previous low energy fracture - Certain drugs - o Glucocorticoids - o Antiepileptic - o Anticoagulant (heparin) - Endocrine diseases - o Hypogonadism - o Hyperthyroidism - o Cushing's disease - o Growth hormone deficiency - o Hyperparathyroidism - Certain medical disorders - o Malnutrition or malabsorption - o Anorexia nervosa - o Inflammatory intestinal disease - o Intestinal resection - o Chronic inflammatory disease (rheumatoid arthritis) - o Transplant patients (solid organs and bone marrow) - o Systemic mastocytosis ## Osteoporosis vs osteomalacia: Disease Info Causes Diagnosis Treatment Logo | Osteoporosis | Weakening of the bones related to reduced bone density | • Long-term high dose corticosteroids use • Certain medications for inflammatory, endocrine, or malabsorption problems • Family history • Low BMI • Drinking/smoking | • Use risk assessment tools to predict the likelihood of a fracture • DEXA scanning can look at bone density. Compared against a peer and a young, healthy adult. • Score of >-1=normal • Score of -1 to -2.5 =osteopenia • Score of <-2.5 =osteoporosis | • Bisphosphonates • Calcium and vitamin D supplements • PTH • Selective estrogen receptor modulators • Hormone replacement treatment | |----------------|----------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Osteomalacia | Inadequate mineralization of the bone due to lack of vitamin D and calcium | • Insufficient dietary intake • Faulty vitamin D metabolism • Renal tubular acidosis • Malnutrition during pregnancy • Chronic kidney failure • Bone tumor induced • Celiac disease | • Very low vitamin D concentration • Pseudo fractures and protrusion acetabula on radiographic images | Nutritional osteomalacia: • Increase dietary intake • Increase outdoor time • Supplementation of vitamin D Malabsorption osteomalacia: • Injected or daily oral dosing of vitamin D • Easily treated if caught early Osteomalacia due to other conditions: • Treat other conditions | ## Limping child ## Case: - 3yr old boy - Pain and limping left leg - Had fevers and cold 2 weeks ago - On examination, temp. 38.7 ℃ - In pain - Crying - Reluctant to move leg Photograph Bar code ## History: - Did he fall - Details of cold - Other symptoms, e.g. other joints affected or fever, weight loss - Has he had this before? - Other medical history - Family history of joint problems ## Causes of limping child: - <4 years old: - o Transient synovitis - o Osteomyelitis/septic arthritis - o Juvenile idiopathic arthritis - o Non-accidental injury - o Referred pain from limb - o Leukemia - o Eosinophilic granuloma - o Metastases neuroblastoma - 4-10 years: - o Transient synovitis - o Perthes disease - o Osteomyelitis/septic arthritis - o Leukemia - o Ewing - 10-16 years - o Slipped femoral epiphysis - o Avulsion fractures - o Osteomyelitis/septic arthritis - o Leukemia - o Osteoid osteoma - o Ewing - o Osteosarcoma ## Tests for limping child: - Bloods: FBS, Esr, CRP, renal function - Autoantibodies - X-ray of leg or hip - MRI Bar code ## Treatment: - Transient synovitis - o Rest and NSAIDs - o Follow fever curve - o Close observation for: - Persistent/worsening limping - Fever - Signs of systemic illness - Septic arthritis - o Drainage in all cases - o Multiple aspirations and irrigations - Unstable patient, gonococcal infection - o Arthroscopic drainage - o Open surgical drainage - o IV antibiotics ## Adulthood joint infection ## Case: - 60 yr old man - 3 days red hot swollen knee - No injury - Feels shivery - Diabetic ## What to ask: - Describe what you see - How did the knee swelling start? - Is there any trauma? - Has he had it before? - What is his past medical history? ## Tests: - Bloods: FBS, Esr, CRP, renal function - Urate - If diabetic, glucose and HbA1c - Autoantibodies - X-ray of the knee - Aspirate joint and send fluid for culture - MRI Photograph Bar code How bacteria changes joint fluid and blood: Change in color and consistency of joint fluid. In the presence of infection, it would look turbid or cloudy, perhaps darker, presence of pus, increased viscosity, and large volumes of effusion from swellings. How will this be reflected in blood tests and joint fluid examinations: Inflammatory markers within the blood tests include white blood cell count, Esr, and CRP. Joint fluid should be aspirated and sent for MC&S, gram staining and to rule out crystal arthropathy like gout/pseudogout. What are the different routes of spread of bacteria: Inoculation, blood, from bone. ## Treatment: - Aspirate - Then antibiotics - If confirmed infection, washout with keyhole arthroscopy - Continue antibiotics ## Intro to Rheumatology Rheumatology is the specialty focusing on diseases of the musculoskeletal system (bones, joints, ligaments, muscles, and tendons). Most are joint diseases. Joints can be classified based on structure or function . In terms of structure, they can be fibrous joints , which have no space between the bones (sutures in the skull, syndesmosis (sheet of connective tissue) in the tibia, and fibula (ankle) joint), cartilaginous joints , in which the bones are connected by cartilage (joints between spinal vertebrae), or synovial joints , which have a space between the adjoining bones (synovial cavity) that is filled with synovial fluid (knee joint). In terms of function, they can be synarthroses , which generally allow no movement (fibrous and cartilaginous joints), amphiarthroses , which allow very limited movement (fibrous and cartilaginous joints), or diarthroses , which allow free movement of the joints (synovial joints). A synovial joint consists of the adjoining bones lined by articular cartilage contained in the synovial cavity. The synovial cavity is lined internally by the synovium, which is a 1-3 cell thick lining containing macrophage-like phagocytic cells (type A synoviocytes), fibroblast-like cells (type B synoviocytes) that produce hyaluronic acid to lubricate the joint, and type I collagen. The synovial fluid is a hyaluronic acid-rich viscous fluid that lubricates the joint. Cartilage is composed of chondrocytes and extracellular matrix: type II collagen, water, and proteoglycans (mainly aggrecan). Aggrecan is characterized by its ability to interact with hyaluronic acid to Bar code form large proteoglycan aggregates. Cartilage is avascular , which means that it has no blood supply and therefore doesn't heal well when there is an injury. Arthritis = disease of the joints. It can be divided into osteoarthritis (degenerative arthritis → wearing out of cartilage) and inflammatory arthritis (the main type is rheumatoid arthritis). Osteoarthritis is characterized by cartilage being worn out and attempts of bony remodeling, leading to bone spurs. It is more prevalent in older people, people with previous joint trauma, and jobs involving heavy manual labor. It has a gradual onset, as it is a slowly progressive disorder. This wearing out of cartilage causes some inflammation, potentially leading to effusion (movement of fluid from its usual situation, to form a collection elsewhere; bones can move because of this as well -ballotable ) . It mainly affects the hand joints , spine , and weightbearing joints of the lower limbs (knee, hip). Its symptoms include joint pain (worse with activity, better with rest, worse during the end of day), joint crepitus (creaking, cracking grinding sound on moving affected joint), joint instability, joint enlarge ment (e.g. Heberden's nodes), joint stiffness after mobility, and limitation of range motion. It is diagnosed through looking at the joint (are there visible abnormalities), feeling (feeling fluid on joint), move (are there movement restrictions), special tests, X-rays, where you can see a narrowing of the joint space, subchondral bony sclerosis (increased white appearance), osteophytes (bone spurs), and subchondral cysts. Risk factors include age, genetics, high BMI, trauma, overload, mechanical constraints, heredity, female gender, menopause, osteonecrosis, leg bone malalignement, estrogen deficiency, metabolic syndrome, advanced hip osteoarthritis caused by spondylarthritis or rheumatoid arthritis, injury, metabolic diseases, infectious diseases involving the bone, and rheumatoid arthritis sequellae. Management includes conservative: weight loss, analgesics (oral/topical NSAIDs), physiotherapy, walking aids, avoidance of exacerbating activity, injections (steroid, viscosupplementation, lubrication gel, platelet rich plasma, stem cells), operative: knee/hip replacement, knee/big toe realignment, excise (toe), fuse (big toe), arthroscopy if loose bone in joint, denervate (wrist). A conservative management might look like this: - Diet plan - Strengthening exercises - o Decreases pain and increases function - o Physical training rather than passive therapy - o General program for muscle strengthening - Warm-up with ROM stretching - Step 1: Lift the body part against gravity, begin with 6 to 10 reps - Step 2: Progressively increase resistance with free weights or elastic bands - Cool-down with ROM stretching - Reconditioning exercises - o Low-impact, continuous movement exercise for 15-30 mins 3 times per week - Fitness walking: increase endurance, gait speed, balance, and safety - Aquatics exercise programs -group support - Exercycle with minimal or no tension - Treadmill with minial or no elevation Bar code Photograph Osteophytes at the DIP joints are termed Heberden's nodes Photograph Osteophytes at the PIP joints are termed Bone spurs (osteophyte) Photograph Photograph Inflammatory arthritis can be caused by infection (septic arthritis, tuberculosis), crystal arthritis (gout, pseudogout), or immune-mediated (autoimmune -rheumatoid arthritis, psoriatic arthritis, reactive arthritis…). Septic arthritis is caused by a bacterial infection of a joint (usually through hematogenous (blood) spread). Immunosuppression, pre-existing joint damage, and intravenous drug use increase the risk of septic arthritis. It is a medical emergency since if left untreated it will lead to rapid destruction of the joint. Usually, only 1 joint is affected -monoarthritis , but with gonococcal septic arthritis, multiple joints can be affected -polyarthritis but it is less likely to cause joint destruction. Other organisms that can cause septic arthritis are staphylococcus aureus and streptococci. Septic arthritis is diagnosed through a joint aspiration that is cultured and Gram stained. Treatment involves a surgical lavage of the joint and intravenous antibiotics. Septic arthritis should be considered in any patient with acute painful, red, hot swelling of a joint, especially if there is a fever. Crystal arthritis happens when crystals deposit in joints, resulting in an inflammatory reaction. It can be divided into gout and pseudogout. Gout is caused by the deposition of urate (uric acid) crystals. High uric acid levels (hyperuricemia is a risk factor for gout; hyperuricemia is caused by genetic tendency, increased intake of purine-rich foods and drinks (e.g. beer), and reduced excretion (kidney failure). Pseudogout is caused by the deposition of calcium pyrophosphate dihydrate (CPPD) crystals. Its risk factors include background osteoarthritis, elderly patients, and intercurrent infection. Bar code Lack of space indicates loss of articular cartilage leading to Gout typically presents as an acute monoarthritis of rapid onset. It usually affects the first metatarsophalangeal joint (podagra) and joints in the foot, ankle, knee, wrist, finger, and elbow. Crystal deposits (tophi) may also develop around the hands, feet, elbows, and ears and appear yellowish. Gout can lead to erosion of the joints, looking like rat bites in an X-ray. Photograph [x-rays show juxta-articular 'rat bite' erosions at the MTPJ of the great toe Photograph Crystal arthritis is diagnosed by aspirating fluid from the affected joint and examining it under a microscope using polarized light. In gout, the crystals are needle-shaped with negative birefringence. In pseudogout, the crystals are rhomboid-shaped with positive birefringence. The most common form of immune-mediated inflammatory joint disease is rheumatoid arthritis . This is a chronic autoimmune disease characterized by pain, stiffness, and symmetrical synovitis (inflammation of the synovial membrane). In rheumatoid arthritis, the synovial membrane is inflamed, causing the synovium to become a proliferated mass of tissue (pannus). This happens due to neovascularization, lymphangiogenesis, and inflammatory cells (activated B and T cells, plasma cells, mast cells, and activated macrophages). This happens due to a cytokine imbalance where there is an excess of pro-inflammatory vs anti-inflammatory cytokines. Tumor necrosis factor-alpha (TNF α ) is the dominant pro-inflammatory cytokine in the rheumatoid synovium and its pleotropic actions (affects multiple processes), which are detrimental in this setting. The key ones are the activation of osteoclasts, which causes bone erosion and resorption, effects on synoviocytes cause joint inflammation, which causes pain and joints swelling, and effects on chondrocytes, which cause cartilage degradation, leading to joints narrowing. ## The key features of rheumatoid arthritis are: - Chronic arthritis - o Polyarthritis -usually of small joints of the hand and wrist but can also affect large joints - o Symmetrical (left and right side of the body are equally affected) - o The primary site of pathology in rheumatoid arthritis is in the synovium, which includes synovial joints, tenosynovium joints surrounding tendons, and bursa. - o Early morning stiffness in and around joints - o May lead to joint damage and destruction -joint erosions on radiographs - Extra-articular disease can occur - o Fever, weight loss, and general malaise (not feeling well) - o Subcutaneous rheumatoid nodules -characterized by a central area of fibrinoid necrosis surrounded by histiocytes and a peripheral layer of connective tissue. It is associated with severe disease, extra-articular manifestations, and rheumatoid factor. - o Others are rare; e.g. vasculitis (inflammation of blood vessels), episcleritis (inflammation of the eye), neuropathies, amyloidosis (if chronic untreated inflammation), lung dise ase (nodules, fibrosis, pleuritis), and Felty's syndrome (triad of splenomegaly, leukopenia, and rheumatoid arthritis) - Rheumatoid factor may be detected in blood - o Autoantibody against IgG -should call this rheumatoid antibody instead of factor. Logo The image is a composite illustrating the differences between normal joints and those affected by rheumatoid arthritis (RA). - The top part shows a labeled diagram of a joint in two states: - Normal joint: includes synovial membrane, cartilage, synovial fluid, and capsule. - Rheumatoid arthritis joint: showing synovitis (inflammation of synovial membrane), bone erosion, pannus (inflamed tissue over cartilage), and cartilage degradation leading to joint space narrowing. - The bottom part consists of clinical images showing various manifestations of RA: - Synovial joints with deformities. - Tenosynovium affecting surrounding tendons. - Bursa inflammation. - Episcleritis, an eye inflammation related to RA. - Vasculitis causing digital ischemia, indicated by finger discoloration. - Rheumatoid nodules in hands. - Inflamed or swollen elbow joint. These visuals collectively highlight the pathological changes and clinical presentations associated with rheumatoid arthritis. Screenshot from computer Rheumatoid nodules in the hands 2 types of antibodies are commonly found in the blood of RA patients: - Rheumatoid factor - o Antibodies that recognize the Fc portion of IgG as their target antigen - o Typically IgM anti-IgG antibodies - Antibodies to citrullinated protein antigens (ACPA) - o Antibodies to citrullinated peptides are highly specific for RA - Can become anti-cyclic citrullinated peptide antibody (anti-CCP antibody) - o Citrullination of peptides is mediated by the enzymes peptidyl arginine deiminases (PADs), converting arginine into citrulline. Bar code The management of RA aims to prevent joint damage but it requires recognition of symptoms, referral, and diagnosis, and prompt initiation of treatment, which is aggressive to suppress inflammation. Joint destruction = inflammation × time . The drug treatment involves the use of disease-modifying anti-rheumatic drugs (DMARDs), which control the disease process.1 st line treatment involves the use of methotrexate (folate antagonist) in combination with hydroxychloroquine or sulfasalazine. 2 nd line treatment involves biological therapies, which offer potent and targeted treatment, or new therapies like Janus Kinase inhibitors. Glucocorticoid therapy has important roles but long-term use must be avoided because of sideeffects. An MDT approach is also important (physiotherapy, occupational therapy, hydrotherapy, surgery…). Biological therapies are proteins (usually monoclonal antibodies) that specifically target a protein like an inflammatory cytokine. These include inhibition of TNF α , B cell depletion (from peripheral blood), modulation of T cell co-stimulation (stops T cell stimulation), and inhibition of IL-6 signaling. The image compares Rheumatoid Arthritis (RA) and Osteoarthritis (OA) through tables, X-rays, and a joint diagram. Top-left table highlights clinical differences: - Age at onset: RA (30-50), OA (>50) - Speed of onset: RA rapid, OA slow - Joint pattern: RA bilateral/symmetric, OA asymmetric - Movement effect: RA often better, OA often worse - Morning stiffness: RA >1 hour, OA uncommon - Affected joints: RA PIP, MCP; OA DIP, thumb CMC - Wrist/elbow involvement: RA common, OA uncommon - Systemic symptoms: RA common, OA not present - Joint swelling: RA effusion/red/warm, OA bony - ESR/CRP: RA elevated, OA normal - Serology: RA positive RF, OA negative Middle table compares radiographic features: - Joint space narrowing: Yes in both RA and OA - Subchondral sclerosis: No in RA, Yes in OA - Osteophytes: No in RA, Yes in OA - Osteopenia: Yes in RA, No in OA - Bony erosions: Yes in RA, No in OA Top-right X-rays: - RA shows joint deformities in MCP and PIP joints - OA shows changes in DIP joints with osteophyte formation Bottom diagram of knee joint damage: - OA side: cartilage breakdown, eroding meniscus, narrowed joint space, bone spurs - RA side: bone erosion, swollen inflamed synovial membrane, cartilage wearing away, bony ankylosis Abbreviations explained: ESR - erythrocyte sedimentation rate, CRP - C-reactive protein, PIP - proximal interphalangeal joint, MCP - metacarpophalangeal joint, DIP - distal interphalangeal joint, CMC - carpometacarpal joint, RF - rheumatoid factor. Overall, the image distinguishes RA and OA in clinical presentation, biochemical markers, radiologic features, and joint pathology. Table Psoriatic arthritis can happen to psoriasis patients. Unlike RA, rheumatoid factors are not present (seronegative). It has varied clinical presentations, but the classical one is asymmetrical arthritis affecting the interphalangeal joints, but can also manifest as symmetrical involvement of small joints (rheumatoid pattern), spinal and sacroiliac joint inflammation, oligoarthritis of large joints, and arthritis mutilans (severe, patient is left with shorter fingers and excess skin). Bar code The image shows two X-ray images of human hands labeled with "R" for the right hand. The text on the image states: - "Asymmetrical pattern of joint involvement" - "Erosions of interphalangeal joints (IPJs)" - "MCPJs not affected (unlike RA)" One arrow points to an erosion on an interphalangeal joint of the right hand, another arrow points to the thumb indicating joint changes, and a horizontal bar highlights the metacarpophalangeal joints (MCPJs) in both hands showing no involvement. This suggests a condition characterized by asymmetrical joint involvement and erosions mainly in the interphalangeal joints, sparing the MCP joints, which differentiates it from rheumatoid arthritis (RA). Photograph Reactive arthritis is another form of seronegative arthritis. This is a sterile inflammation in the joints following infection, especially urogenital and gastrointestinal infections. Important extraarticular manifestations include enthesis (tendon inflammation), skin inflammation, and eye inflammation. Reactive arthritis may be the first manifestation of HIV or hepatitis C infection. It commonly occurs in young adults with genetic predisposition and an environmental trigger. The symptoms appear 1-4 weeks after infection; this infection may be mild. | | Septic arthritis | Reactive arthritis | |------------------------|----------------------|----------------------| | Synovial fluid culture | Positive | Sterile | | Antibiotic therapy | Yes | No | | Joint lavage | Yes for large joints | No | Systemic Lupus Erythematous (SLE) is another type of immune-mediated inflammatory joint disease. It is a multi-site inflammation that can affect almost any organ but often affects the joints, skin, kidneys, hematology, lungs, and CNS. A classical sign of Lupus is a malar or 'butterfly' rash, which is usually triggered by sun exposure. Lupus is associated with autoantibodies that are directed against components of the cell nucleus (nucleic acids and proteins). These autoantibodies can be used diagnostically; clinical tests include: - Antinuclear antibodies (ANA) - o High sensitivity for SLE but not specific (negative rules out SLE but positive doesn't mean SLE) - Anti-double stranded DNA antibodies (anti-dsDNA Abs) - o High specificity for SLE in the context of the appropriate clinical signs Females are more affected than males (F:M ratio 9:1), it presents between 15-40 yrs old, and there is an increased prevalence in populations of African and Asian ancestry. Logo