IUHS Student-2-Student USMLE Step 1 Recall
Musculoskeletal
Joints, Etc.
Osteoarthritis
osteoarthritis, also called degenerative joint diseaes, is the most common type of joint diseaes...it is characterized by the progressive erosion of articular cartilage...
the tern osteoarthritis implies an inflammatory disease...although inflammatory cells may be present, osteoarthritis is considered to be an intrinsic disease of cartilage in which biochemical and metabolic alterations result in its breakdown......
Osteoarthritis usually involves a larger joint. The pain usually diminishes with movement, but recurs with reuse or prolonged use of the affected joint
Osteoarthritis is very common. The articular surface becomes worn or damaged with time, leading to pain and loss of mobility.
subchondral sclerosis and formation of osteophytes...
the prevalence increases exponentially beyond the age of 50...about 80-90% of individuals, of both sexes, have evidence of osteoarthritis by the time they reach age 65...
the age-related changes in cartilage include alterations in proteoglycans and collagen, which decrease tensile strength and shorten fatigue life...
chondrocytes
play a role in the process and constitute the cellular basis of the disease...chondrocytes
in osteoarthritic cartilage produce IL-1 and TNF-alpha, which are known to
stimulate the production of catabolic metalloproteinases, and inhibit the
synthesis of both type 2 collagen and proteoglycans...
the effects of these cytokines are potentiated b/c their receptors show increased sensitivity...other mediators, such as prostaglandin derivatives and IL-6, also have a role in this cascade of matrix degradation...
most of these cytokines also have proinflammatory properties, and inflammatory cells are present in many osteoarthritis joints...
Osteoarthritis is a degenerative, non-inflammatory process seen most often with aging, particularly with joints that get a lot of use. Pain is the major problem.
subchondral sclerosis and formation of osteophytes.
symptoms include deep, achy pain that worsens with use, morning stiffness, crepitus, and limitation of range of movement...
impingement on spinal foramina by osteophytes results in cervical and lumbar nerve root compression with radicular pain, muscle spasms, muscle atrophy, and neurologic deficits...
the joints commonly involved include the hips, knees, lower lumbar and cervical vertebrae, proximal and distal interphangeal joints of the fingers, first carpometacarpal joints, and first tarsometatarsal joints of the feet...
characteristic in women, but not in men, are Heberden nodes in the fingers representing prominent osteophytes at the distal interphalangeal joints...
Degenerative osteoarthritis is a common and progressive condition that becomes more frequent and symptomatic with aging. There is erosion and loss of articular cartilage
subchondral sclerosis and formation of osteophytes...
Rheumatoid Arthritis (RA)
RA is a chronic systemic inflammatory disorder that may affect many tissue and organs, skin, blood vessels, heart, lungs, and muscles, but principally attacks the joints, producing a nonsuppurative proliferative synovitis that often progresses to destruction of the articular cartilage ankylosis of the joints...
about 1% of the world's population is afflicted by RA, women three to five times more often than men...the peak incidence is in the twenties and forteis, but no age is immune...
proliferative synovitis with pannus formation...
nodule shows an area of central necrosis surrounded by palisading epithelioid cells...
Plasma cells and lymphocytes...
rheumatoid arthritis can be complicated by amyloidosis of the reactive systemic variety with Serum amyloid-associated protein contributing to amyloid deposition in a variety of organs...
initially
the synovium becomes grossly edematous, thickened, and hyperplastic,
transforming its smooth contour to one covered by delicate and bulbous fronds...
infiltration of synovial stroma by a dense perivascular inflammatory infiltrate composed of lymphoid follicles (mostly CD4+ helper T cells), plasma cells, and macrophages filling the synovial stroma...
increased vascularity owing to vasodilation and angiogenesis, with superficial hemosiderin deposits..
aggregation of organizing fibrin covering portions of the synovium and floating in the joint space as rice bodies...
accumulation of neutrophils in the synovial fluid and along the surface of synovium but usually not deep in the synovial stroma...
osteoclastic activity in underlying bone, allowing the synovium to penetrate into the bone forming juxta-articular erosions, subchondral cysts, and osteoporosis...
pannus formation,
pannus is a fibrocellular mass of synovium and synovial stroma consisting of
inflammatory cells, granulamatous tissue, and fibroblasts, which causes erosion
of the underlying cartialge...
nodule shows an area of central necrosis surrounded by palisading epithelioid cells...
Plasma cells and lymphocytes...
rheumatoid nodules are the most common cutaneous lesion...they occur in approximately 25% of patients, usually those with severe disease, and arise in regions of the skin that are subjected to pressure, including the ulnar aspect of the forearm, elbows, occiput, and lumbosacral area...
rheumatoid nodules are firm, nontender, and round to oval and in the skin arise in the subcutaneous tissue...
microscopically they have a central zone of fibrinoid necroiss surrounded by a prominent rim of epitheliod histiocytes and numerous lymphocytes and plasma cells...
nodule shows an area of central necrosis surrounded by palisading epithelioid cells...
although much remains uncertain, it is currently believed that RA is triggered by exposure of an immunogenetically susceptible host to an arthritogenic microbial antigen...
in this manner, an acute arthritis is initiated, but it is the continuing autoimmune reaction, the activation of CD4+ helper T cells, and the local release of inflammatory mediators and cytokines that ultimately destroys the joint...
involved therefore in the pathogenesis are genetic susceptibility, a primary exogenous arthritiogen, an autoimmune reaction to joint components, and mediators of the joint damage...
Genetics - HLA-DR1 or 4....
Microbial - strong correlation to EBV b/c of autoimmunity to type 2 collagen...
Autoimmune - T cells, CD4+ memory cells, ICAM-1 leads to further activation of CD4 and T cells, cytokines, IL-15, B cells, IgG...TNF, IL-1, IL-6, IL-15, Interferon-gamma, GM-CSF, TFG-beta, proteases, elastases, TNF-alpha
nodule shows an area of central necrosis surrounded by palisading epithelioid cells...
4 of the next seven must be present:
1) morning stiffness...
2) arthritis in three or more joint areas...
3) arthritis of hand joints...
4) symmetric arthritis...
5) rheumatoid nodules...
6) serum rheumatoid factor...
7) typical radiographic changes...
nodule shows an area of central necrosis surrounded by palisading epithelioid cells...
Plasma cells and lymphocytes...
treated with methotrexate...
autoantibodies directed against IgG...
Gout
gout is a common end point of a group of disorders that produce hyperuricemia...it is marked by transient attacks of acute arthritis initiated by crystallization of urates within and about joints leading eventually to chronic gouty arthritis and the deposition of masses of urates in joints and other sites creating tophi...
tophi represent large aggregates of urate crystals and the surrounding inflammatory reaction...most, but not all, patients with chronic gout also develop urate nephropathy....
long, needle-shaped, negatively birefringent crystals of monosodium urate preceipitate to form chalky white deposits...
PseudoGout - deposition of calcium pyrophosphate dihydrate (CPPD) in synovial membranes...CPPD crystals are not needle shaped like urate crystals, but are short, stubby, and
postive birefringement rhomboid...
central
to the pathogenesis of the arthritis is
precipitation of monosodium urate crystals into the joints...synovial
fluid is a poorer solvent for monosodium urate than plasma, and so with
hyperuricemia the urates in the joint fluid become supersaturated, particularly
in the peripheral joints...
with prolonged hyperuricemia, crystals and microtophi of urates develop in the synovial lining cells and in the joint cartilage...
inorganic crystals, including monosodium urate, can stimulate the formation of specific antibodies, which then can rapidly accelerate the formation of new crystals...
the released crystals are chemotactic to leukocytes and also activate complment, with the generation of C3a and C5a leading to the accumulation of neutrophils and macrophages in the joints and synovial membranes...
phagocytosis of crystals induces release of toxic free radicals and leukotrienes (LTB4)...activatd neutrophils release destructive lysosomal enzymes, and the macrophages and synviocytes secrete a variety of mediators, which further intensify the inflammatory reaction and augment the injury to the articular structures...
approximately 25% of patients with gout have kidney stones...