Joint Anatomy and Histology; Pathology of Osteoarthritis and Rheumatoid Arthritis Flashcards
What is the most common type of movable joint and what do the cells secrete to maintain it?
Diarthrodial / synovial joint
Synovial cells secrete hyaluronic acid to make the ultrafiltrate of plasma that is secreted into the joint even thicker.
What type of joint does the intervertebral disc make?
Amphiarthrodial -> limited mobility
What are the two components of the intervertebral disc? What do they attach to?
- Annulus fibrosus - fibrocartilage, made from sclerotome. Attach to vertebral bodies via Sharpey fibers.
- Nucleus pulposus - Gelatinous core of proteoglycans and water, which resists compression. Separated from vertebral bodies via hyaline cartilage (articular).
What are the two types of synarthroses and an example of each?
- Fibrous - i.e. skull sutures
2. Cartilaginous - i.e. pubic symphysis
How does hyaline articular cartilage receive its nutrients and what is it good for resisting mechanically?
Receives its nutrients from diffuse of nutrients from synovial fluid
Good for resisting compression
What is hyaline cartilage made out of that makes it good at resisting compression?
Proteoglycans
-> i.e. aggrecan molecules bound to hyaluronic acid, with carbohydrate side chains of keratan and chondroitin sulfate
Highly charged and attract water
Also has type II collagen running superficially parallel and deeply perpendicular to the joint interface
What is the bone-hyaline cartilage interface like? Why is it like this?
Noncalcified cartilage -> tidemark (where calcified cartilage meets noncalcified cartilage) -> calcified cartilage -> subchondral bone
This prevents weakness at the bone-cartilage interface
What is fibrocartilage made of and what is it good for? Where is it found?
Made of type 1 collagen as well as hyaline cartilage (a mix of the two). Good for resisting tension
Found in the menisici of the knee, annulus fibrosus, and insertions of ligaments / tendons on bone
What structures does the synovial membrane line?
Inner surface of the joint capsule and other intra-articular structures EXCEPT articular cartilage and menisci
Bursae
Tendon sheaths
What is the structure of the synovial membrane (two layers)?
- Synovial lining cells -> a few layers thick, producing hyaluronic acid, phargocytosing debris, and mediating nutrient and waste exchange between blood and synovial fluid
- Subsynovial loose connective tissue -> with immune cells, capillaries, lymphatics, and nerves. Regulates the synovial fluid movement.
How does cartilage change as you age?
Cartilage loses water content due to change in composition of proteoglycan molecules
What is primary vs secondary osteoarthritis and who gets secondary?
Primary = idiopathic, associated with wear and tear
Secondary - Happens in younger individuals with previous joint injury or deformity, or a systemic disease affecting the joints
What is the pattern of joint involvement in primary osteoarthritis? Men vs women?
Oligoarticular, affecting especially the weight-bearing joints.
Knees and hands - affected in women. Hands are very familial.
Hips - affected in men
Cervical and lower lumbar vertebrae - affected in both
First tarso-metatarsal joint -> from stepping off of foot
What pathology is seen in the articular cartilage in early vs late osteoarthritis?
Early - proliferation of chondrocytes with secretion of inflammatory mediators -> alteration in composition of cartilaginous matrix. Inflammation begins in synovium (mild, chronic “-itis”) and underlying subchondral bone.
Late - Marked loss of cartilage and abnormalities of subchondral bone. Cartilage shows fissures and clefts, called “fibrillation”
What pathologic features characterize the joint in general in osteoarthritis?
- Joint space narrowing -> cartilage thinning leads to less radiolucent space between bones
- Joint mice (loose bodies) - sloughed cartilage +/- bone into joint
What happens to the exposed subchondral bone in osteoarthritis?
- Friction with opposing surface -> bone becomes eburnated and sclerotic
Eburnated means smooth and polished. - Formation of subchondral cysts -> small fractures in bone allow synovial fluid to enter bone.
What are osteophytes? Do they have cartilage on them?
Bone spurs -> reactive bony outgrowths at the margins of the articular surface
They are capped by cartilage. They grow laterally because they can’t make bone on the weightbearing surface (they would get crushed).
What are the clinical symptoms of osteoarthritis, and what problems can osteophytes of the vertebrae cause?
Insidious onset of joint pain worse with activity, morning stiffness (<30 min), and decreased range of motion
Vertebral osteophytes -> can impinge on spinal nerve roots and cause neural problems
What are osteophytes of the hands in osteoarthritis called?
PIP - Bouchard nodes (think BP)
DIP - Heberden’s nodes
What genetic markers are associated with development of rhuematoid arthritis?
- HLA-DRB1 - common epitope for presentation in MHC Class II
- HLA-DR4 - 4 walls in a rheum
- PTPN22 - protein tyrosine phosphatase - plays a role in inhibition of T cell activation. Increased risk if lost.
What is the process by which autoimmunity is thought to arise in RA?
Tissue injury i.e. via bacterial infection in combination with smoking to increase the inflammation -> lysis of cells and exposure of citrullinated self-peptides via MHC -> creation of autoantibodies to citrullinated self antigens
Bacteria also have some epitopes which look like citrullinated peptides as well which may contribute via molecular mimicry
How does cell-mediated immunity play a role in pathogenesis of RA?
- Th1 cells -> secrete IFN-y to activate macrophages and synoviocytes
- Th17 inflammatory cells -> chemotaxis of neutrophils and monocytes
- Macrophages secrete TNFa and IL-1 -> stimulate metalloprotease release by synoviocytes to destroy atrticular cartilage
- Activatd T cells express RANKL -> activate osteoclasts and bone resorption
What are the sensitive and specific antibodies for RA?
Sensitive: anti-CCP (cyclic citrullinated peptides) + rheumatoid factor (IgM or IgA antibodies against the Fc portion of IgG - unclear if involved)
Specific: anti-CCP most specific
What forms cyclic citrullinated peptides?
Arginine residues are post-translationally converted to citrulline.
