Joint Pathology Flashcards
Articular/hyaline cartilage is comprised of
chondrocytes (build and break down matrix), type II collagen (matrix) with GAGs, water (70% by weight)
What is the role of chondrocytes in articular cartilage?
build and break down matrix (collagen type II)
Deep in articular cartilage, collagen fibres are oriented __________ whereas close to the surface they are oriented ___________
perpendicular; parallel (holds everything together)
GAGs are _________ charged
negatively; they repel each other but are held together by collagen
Perfusion of articular cartilage occurs by
compression/decompression w/exercise bc it is avascular
Synovial capsule is comprised of
dense connective tissue
Synovium lines the
joint space, except where there is cartilage; attached to the capsule
Synovial fluid is made up of
plasma filtrate with extra slippery hyaluronic acid produced by the synovium
T/F Synovium is an epithelium
False; it has no epithelial cells, a BM, or desmosomes, etc. It’s more like a dense layer of cellular connective tissue allowing for easy diffusion
Type A synoviocytes
macrophage-like; phagocytes that set off inflammatory reactions
Type B synoviocytes
fibroblast-like; produce hyaluronic acid for lubrication
What is osteoarthritis?
Wear & Tear’ arthritis; degeneration of the joint cartilage that occurs in hard-working joints: hips, knees, hands; or previously injured joints
What causes osteoarthritis?
‘Focal disease of joint cartilage causing it to break down; involves enzymes (collagenases, MMPs) activated from cartilage (layed down by chondrocytes) and cytokines (IL-1) from synovial cells
What are the S&S of osteoarthritis?
Deep achy pain in joints that gets worse with use; reduced ROM of joints; crepitus; osteophytes (Hebbidins nodes at DIPs and Bouchard’s nodes at PIPs); slow, insidious onset; no systemic symptoms
What is the tx for OA?
physio, pain relief & anti-inflams, joint replacement
What is rheumatoid arthritis?
Autoimmune inflammatory arthritis with systemic involvement - can also affect skin, blood vessels, heart, lungs; progressive disease (good chance of being disabled if un-tx for 10yrs +)
What is the cause of RA?
Autoimmune reaction to an unknown antigen; perhaps a viral infection; in genetically suceptible individuals (MHC alleles)
What are the S&S of RA?
Often polyarthritis starts symmetrically in small joints of hands and/or feet (oligo/few or polyarthritis/lot) and progresses to destroy them - DIPs often spared; warm, swollen, tender joints; swelling is rubbery/doughy due to pannus and mononuclear infiltrate; morning stiffness for 1hr+ that eases with activity; systemic symptoms like rheumatoid nodules usually in places of friction eg elbows, fever (cytokines), weight loss, anaemia; destruction and deformity of joints (eg swan neck deformity with fixed hyperextension of PIPs and fixed flexion of DIPs)
What is the tx of RA?
Immune-modulating disease-modifying anti-rheumatic drugs
What is gout?
metabolic disease (not a pimary inflammatory disorder) caused by too much uric acid in the body; acute inflammation in a single joint due to crystallization of uric acid (eg big toe = podagra)
What causes gout?
high uric acid levels; Inflammatory reaction to uric acid cystals precipitating and crystallizing in joints especially those with low pH, fibrous tissue and nucleating agents that are cooler and poorly perfused, especially following alcohol, dehydration, or high-purine diet; crystals activate inflammatory cells, synovial cells, and complement; can progress to chronic, disabling tophaceous gout if left untreated involving multiple joints and recurrent inflammation that can cause damage and pannus formation, as well as tophi (urate deposition in other soft tissues, articular cartilage, capsule, etc.), nephropathy, and kidney stones
What are the S&S of gout?
Can be asymptomatic for 20-30 years then often starts in big toe; acutely inflammed joint that is very painful, often not accompanied by systemic symptoms like fever (would be cause for concern of tophi infection or septic arthritis); may present with tophi if chronic; spontaneous onset of excruciating pain, swelling, heat, and redness, classically in the big toe in early morning
What are the risk factors for gout?
Obesity, rich diet (high purines), high alcohol intake, hypertension, metabolic syndrome; associated with risk of T2DM/insulin resistance, hypertension, heart disease; prevalence is higher in men and increases with age and post-menopause; abnonormalities in uric acid metabolism - increased intake or production of uric acid or reduced excretion through the kidneys; genetics and ethnicity (pacific islanders)
What is the tx for gout?
Anti-inflams, urate-lowering therapy, lifestyle changes
What is the source of damaging enzymes in OA?
chondrocytes - lay down collagenases and MMPs in the matrix to help with normal turnover (usually inactivated)
OA affects which parts of the joint?
capsule, synovium, underlying bone - not just the cartilage
What are the pathological investigations in OA?
no lab dx tests; mostly to R/O inflammatory or rheumatoid arthritis
What is found on X-ray in OA?
X-rays not always necessary; can see loss of cartilage and loss of joint space; osteophytes; subchondral sclerosis, thickening, and cysts - can be used to grade OA but findings don’t always correlate to S&S severity
What are the risk factors for OA?
increasing age (>50% 70+) due to loss of coordination, muscular tone, and regenerative capability of cells; obesity esp knees; previous injury or abnormality of the joint affecting proprioception and weight bearing, alignment, changes joint surface; repeated heavy use of joints through work or recreation; genetic (hands and hips, not knee); most risk factors relate to cartilage damage and decreased repair
What is the pathophysiology of OA?
damage activates chondrocytes causing them to proliferate; actions of enzymes (collagenases and MMPs) and cytokines (IL-1) deplete and unravel matrix (decreased collagen II and GAGs, increased water) releasing more enzymes; loss of mechanical function due to loss of water layer (forces transmitted differently) causing damage to underlying bone - thickening and fractures; fibrillation and erosion of cartilage; bone on bone rubbing causes eburnation (like ivory - thickened, white, shiny) and development of cyts and osteophytes; regenerative processes lead to hypertrophy of cartilage and bone
What is the morphology of OA?
Fibrillation and non-uniform loss of articular cartilage, eburnation and thickening of subchondral bone with subchondral cysts, osteophytes
IL-17 excites
neutrophils
Which cytokine is central to RA?
TNFa; target of antagonist disease-modifying anti-rheumatic drugs
What are the pathological findings in RA?
elevated CRP; FBE shows neutrophils and lymphocytes; rheumatoid factor and anti-CCP are specific tests - don’t need to know; diagnosis is clinical correlation of findings with laboratory and imaging
What are the x-ray findings in RA?
juxta-articular osteopaenia (thin bone around joints); subchondral erosions due to pannus invasion into synovium; uniform joint space loss (in OA it is weight-bearing joint space that is lost);
What are the risk factors for RA?
~1% of pop’n; genetic ~50% of risk - shared epitopes of HLA-DRB1, PTPN-22; female sex (2-5:1); increasing age from ~25 until ~55yo; smoking (RR 1.3-3.5)
What is the pathophysiology of RA?
T helper cells (Th1 & Th17) and acute inflammatory cytokines (IL-1, IL-6, IL-17, TNFa) are induced by the unknown antigen; activates fibroblasts and macrophages from the synovium; increased RANKL and decreased OPG leads to osteoclast activation; induction of B cells to plasma cells; as a result synovium gets hyperplastic and hypertrophic; synovium eventually turns into inflammatory granulation tissue called pannus; MMPs and collagenases released from macrophages cause breakdown of cartilage and bone that destroys the joint
What is the morphology of RA?
inflammatory changes in joints: mononuclear infiltrate (lymphocytes, plasma cells, macrophages) in synovium with germinal centres; hyperplasia of synovium with villus formation into the joint, eventually becoming pannus (inflammatory granulation tissue); neutrophils and fibrin may be found in the joint space as acute inflammation on top of the chronic inflammation but mostly mononuclear infiltrate; pannus invades and erodes bone and cartilage; weakening and damage of ligaments cause joint to fall apart; eventually pannus grows in, destroys cartilage, forming fibrous granulation tissue that ossifies joining the bones together if left untreated; rheumatoid nodules appear as granulomatous inflammation - central necrosis with surrounding epitheliod macrophages, multinucleate giant cells, fibroblasts, and collagen
What are the pathological investigations in gout?
tophus or joint aspiration is gold-standard - looking for negatively birefringent crystals with neutrophils (macroscopic appearance is white and opaque); serum urate levels are confusing because attacks can lower serum levels, and urate-lowering therapy precipitates gout, can have high levels with no gout
What are the radiological findings in gout?
not often done; punched-out erosions with sclerotic, overhanging edges, outside of the joint capsule; sometimes can see tophi which may be calcified; distribution is asymmetric; no loss of joint space and no periarticular osteopaenia
What is the pathophysiology of gout?
crystals activate inflammatory cells, synovial cells, and complement’ production of IL-1, complement activation and chemotaxis; crystals lyse neutrophils when they engulf them, causing them to spill their phagolysozome and inflammatory mediators furthering the inflammatory response
What is the morphology of gout?
long, thin, spiky crystals of uric acid (negatively birefringent in polarised light); tophi appear with granulomatous inflammation around urate deposits (foreign body type granuloma) with epitheliod macrophages, multinucleate giant cells, and surrounding fibrosis; macroscopic appearance is inflammation of the joint - painful, red, swollen
