Chapter 26: Joints Flashcards
What are the 3 major components of hyaline cartilage?
70% H2O + 10% type II collagen + 8% proteoglycans
Which joints are most commonly affected in osteoarthritis in men vs. women?
- Men = hips
- Women = hands and knees
What are the 3 phases of changes to chondrocytes seen with the pathogenesis of osteoarthritis?
- Chondrocyte injury, related to genetic and enviornmental factors
- Early OA: proliferation for remodeling of cartilaginous matrix and secondary inflammatory changes
- Late OA: repetitive injury and chronic inflammation lead to chondrocyte drop out, marked cartilage loss, and extensive subchondral bone changes
Which cytokines and diffusable factors have been implicated in the pathogenesis in osteoarthritis?
- TGF-β –> which induces MMP’s
- TNF
- Prostaglandins
- Nitric oxide
What are 3 characteristic morphological findings of osteoarthritis?
- Hunks of dead cartilage sloughed into the joint –> ‘joint mice’
- Subchondrondal bone exposed and rubbed smooth = eburnation
- Microfractures and cysts develop
- Mushroom-shaped osteophytes (bony outgrowths)
Deep, achy pain that worsens with use, morning stiffness, crepitus, and limitation of ROM is characteristic of what?
Osteoarthritis
What are the prominent osteophytes which may form at the PIP and DIP joints of pt with osteoarthritis called?
- PIP = Bouchard’s nodes
- DIP = Heberden node
Which joint disease may progress to deformity with time and which may progress to fusion?
- OA may progress to joint deformity, not fusion
- RA progresses to fusion
OA is a disease of what vs. RA?
- OA = disease of cartilage
- RA = disease of synovium
Which inflammatory cells may initiate the autoimmune response in RA and how?
CD4+ T helper cell by reacting with an arthritogenic agent, perhaps microbial or a self-antigen
What are the most important cytokines isolated from the inflammed joint in person with RA; what is their role in the disease?
- IFN-γ from TH1 cells activate macrophages and resident synovial cells
- IL-17 from TH17 cells recruit neutrophils and monocytes
- TNF and IL-1 from macrophages stimulate resident synovial cells to secrete proteases that destro__y hyaline cartilage
- RANKL on activated T cells stimulate bone resportion
Which cytokine has been most firmly implicated in the pathogenesis of RA?
TNF
Many of the autoantibodies produced in the lymphoid organs and in the synovium of pt with RA are specific for what?
Citrullinated peptides (CCPs)
What are 2 genetic factors associated with RA?
HLA-DRB1 alleles & PTPN22 gene
What are 5 characteristic histologic features of RA?
- Synovial cell hyperplasia and proliferation
- Dense inflammatory infiltrates of CD4+ cells, B cells, plasma cells, dendritic cells, and macrophages
- ↑ vascularity due to angiogenesis
- Fibrinopurulent exudate on synovial and joint surfaces
- Osteoclastic activity in underlying bone –> periarticular erosions ad subchondral cysts
Which characteristic mass of edematous synovium, inflammatory cells, granulation tissue, and fibroblasts growing over articular cartilage is seen in joints affected by RA?
Pannus
With time in RA, the pannus bridges apposing bones to form what?
Fibrous ankylosis, which eventually ossifies and results in fusion of the bones, called bony ankylosis
Which skin lesions are commonly seen in RA, what is their morphology?
- Rheumatoid nodules: firm, non-tender, and round arising in subcutaneous tissue
- Resemble necrotizing granulomas w/ central zone of fibrinoid necrosis + prominent rim of macrophages, lymphocytes and plasma cells.
Where are rheumatoid nodules most commonly seen?
Extensor surfaces at pressure points
How may the blood vessels of patient with RA be affected and which vessels specifically?
- Risk of acute necrotizing vasculitis of small and large arteries
- May involve the pleura, pericardium or lung evolving into chronic fibrosing process
- Obliterating endarteritis —> peripheral neuropathy, ulcers, and gangrene may occur
Inflammation in the tendons, ligaments, and occassionally adjacent skeletal muscle accompanying RA produces what characteristic findings in the hands?
- Radial deviation of the wRrist
- UlNar deviation of the fiNgers
- Boutonniere: deformity of finger –> hyperextension of DIP w/ flexion of PIP
- Swan-neck: hyperextension of PIP, flexion of DIP
What are the radiographic hallmarks of RA?
Joint effusions and juxta-articular osteopenia w/ erosions and narrowing of the joint space + loss of articular cartilage
Diagnosis of RA, especially with presence of multisystem involvement, is supported by what 3 findings?
- Characteristic radiohgraphic findings
- Sterile, turbid synovial fluid w/ ↓ viscosity, poor mucin clot formation, and inclusion-bearing neutrophils
- Combo of rheumatoid factor and anti-CCP antibody
How do the joints being affected differ between OA and RA?
- OA: usually large, weight bearing joints
- RA: symmetrical pattern w/ small joints affected first
How does activity affect the pain in OA vs. RA?
- OA = worse with activity
- RA = improves with activty, worse with rest
What may develop in the knee as increased intra-articular pressure causes herniation of synovium in some pt’s with RA?
Baker cyst of the posterior knee
Which ocular changes due to blood vessel involvement may be seen with RA?
Uveitis and Keratoconjunctivitis
Which heterogenous group of disorders present with arthritis before age 16 and persist for at least 16 weeks?
Juvenile idiopathic arthritis (JIA)
In what 5 ways is Juvenile idiopathic arthritis (JIA) different than RA?
- Oligoarthritis = more common
- Systemic dz is more frequent
- Large joints affected more often
- Rheumatoid nodules and rheumatoid factor typically absent
- Antinuclear antibody (ANA) is common
What are the 4 features unifying the seronegative spondyloarthropathies?
- Changes in ligamentous attachments rather than synovium
- Involvment of the SI joint +/- others
- Absence of RF
- Association of HLA-B27
What joints involved in ankylosing spondylitis and typical presentation?
- Destruction of articular cartilage and bony ankylosis, typically of sacroiliac and apophyseal joints
- Involvement of SI joint & vertebrae becomes symptomatic in 2nd - 3rd decade of life as LBP and spinal immobility
Who is most affected by reactive arthritis and at what age?
- Men in their 20s or 30s
- Also affects pt’s with HIV
Reactive arthritis most often follows what?
- GU infection –> Chlamydia
- GI infection –> Shigella, Salmonella, Yersinia, or Campylobacter
What are the common early sx’s of reactive arthritis and which joints are most often affected?
- Early sx’s = joint stiffness + LBP
- Ankles, knees, and feet are affected most often; frequently asymmetric
What are the extra-articular manifestations that may be seen with reactive arthritis?
- Inflammatory balanitis
- Conjunctivitis
- Cardiac conduction abnormalities
- Aortic regurgitation
Involvement of the digital tendon sheath in reactive arthritis produces what?
Sausage fingers or toes
What is the typical presenation of enteric associated arthritis, joints involved, and how does it differ in course from reactive arthritis?
- Appears abruptly tends to involve knees and ankles; sometimes the wrists, fingers,andtoes
- Lasts for about a year vs. reactive arthritis which wax and wanes for about 6 weeks
Sx’s of psoriatic arthritis typically manifest when and predominantly consist of what?
- Between ages 30-50 y/o
- Predominantly a peripheral arthritis of hands and feet
- DIP joints affected 1st, asymmmetric distribution –> “pencil in cup” deformity
Gonococcal arthritis has a predilection for which sex; how does the presenation differ from other casuses of suppurative arthritis?
- Mainly sexually active women
- Presents in a more subacute fashion
What is the classic presentation of suppurative arthritis and what are the systemic findings?
- Sudden development of acutely painful and swollen joint w/ restricted ROM
- Fever + leukocytosis + ↑ ESR
90% of nongonococcal cases of suppurative arthritis involve how many joints and which joints are most frequently affected?
Single joint, most commonly the knee > hip > shoulder > elbow > wrist > SC joint
Pt’s with deficiency of complement MAC (C5, C6, C7) are at greater risk for suppurative arthritis from which organism?
Gonoccocal infections
How is suppurative arthritis diagnosed?
Joint aspiration yielding purulent fluid in which causal agent is identified
Which joints are most often affected in Lyme Arthritis and what is course of the disease?
- Primarily large joints –> knee > shoulder > elbow and ankles
- 1-2 joints at a time, attacks last few weeks to months, migration to new sites
How may lyme arthritis be diagnosed?
- Spirochetes identified in joints w/ arthritis in about 25% of cases
- Serologic testing for anti-Borrelia antibodies
Hyperuricemia is a plasma urate level of what?
>6.8 mg/dL
Which syndrome is due to a complete absence of HGPRT interrupting the purine salvage pathway resulting in hyperuricemia?
Lesch-Nyhan syndrome –> Mental retardation + Self-mutilation + 2’ gout
Describe the inflammatory response following the precipitation of MSU crystals into joints and contribution to gout.
- Inflammasome recognizes crystals –> activates caspase-1 —> prod. of IL-1β —> accumulation of neutrophils + MΦ’s in joint
- Urate crystals may also activate complement –> chemotactic complement byproducts
Describe how the solubility of MSU in a joint is modulated by both temperature and the chemical composition of the fluid?
- Synovial fluid is inherently a poorer solvent for MSU than plasma
- Lower temp. of peripheral joints also favors precipitation
How long does it take a patient with hyperuricemia to typically develop gout?
20-30 years
What are the 4 distinct morphological changes in gout?
1) Acute arthritis
2) Chronic tophaceous arthritis
3) Tophi in various sites
4) Gouty nephropathy
What is the pathognomonic hallmark of gout; where are they seen?
- Tophi = large aggregations of urate crystals surrounded by intense inflammatory rx of foreign body giant cells
- Articular cartilage, ligaments, tendons, and bursae; sometimes soft tissues (earlobes, fingertips) or kidneys
Which drug may reduce the excretion of urate and contribute to the development of gout?
Thiazide diuretics
Which heavy metal toxicity may contribute to gout?
Lead toxicity –> saturnine gout
Where do MSU crystals deposit in kidney and what are some of the complication which arise with gouty nephropathy?
- Deposit in the renal medullary interstitium or tubules
- Complications = uric acid nephrolithiasis + pyelonephritis, particularly when urates induce urinary obstruction
- 20% of chronic gout –> death due to renal failure
In the final stage of gout progression, chronic tophaceous gout, what will characteristically be seen on radiographs?
Juxta-articular bone erosion due to osteoclastic bone resorption and loss of joint space
When does gout vs. pseudo-gout typically develop and in whom?
- Gout = more common in men and after age 30
- Pseudo-gout = both sexes equally affected and occurs in pt’s >50 y/o becoming more common w/ ↑ age
An autosomal dominant variant of pseudo-gout leading to the development earlier in life is due to germline mutations in what?
Pyrophosphate transport channel
Secondary form of pseudo-gout is associated with what underlying conditions?
- Previous joint damage
- Hyperparathyroidism
- Hemochromatosis
- Hypomagnesemia
- Ochronosis
- Diabetes
What do the crystals of pseudo-gout form and how are they seen histologically?
- Form chalky, white, friable deposits
- Seen histologically as oval blue-purple aggregates
- Individual crystals are rhomboid and positively birefringent
Where is a common location for ganglion cyst’s to arise, how to they appear, and arise as a result of what?
- Around joints of wrist
- Firm, fluctuant, pea-sized translucent nodule
- Arise as result of cystic or myxoid degeneration of CT; hence the cyst wall lacks a cell lining
What is a synovial cyst and what is a common example of one?
- Herniation of the synovium thru a joint capsule or massive enlargement of a bursa
- Baker cyst seen in popliteal space in setting of RA
What are common locations to find the diffuse vs. localized type of tenosynovial giant cell tumor; occur in which age group?
- Diffuse = tends to involve large joints; commonly knee (80%)
- Localzied = usually occurs as discrete nodule attached to tendon sheath, commonly in hand
- Both occur in pt’s 20-40 y/o; both sexes equally
Which reciprocal translocation is seen with tenosynovial giant cell tumors and what does this mutation cause?
- t(1;2)(p13;q37) —> fusion of type VI collagen α-3 promoter upstream of the coding sequence of M-CSF
- Leads to overexpression of M-CSF –> stimulates macrophage proliferation
What is the behavior of the localized type of tenosynovial giant cell tumors; how common are they?
- Manifests as solitary, slow-growing, painless mass that frequently involves tendon sheaths along wrists and fingers
- Most common mesenchymal neoplasm of hand
What is characteristic morphology of the diffuse type of tenosynovial giant cell tumor?
Joint synovium converted into tangled mat by red-brown folds + finger-like projections and nodules
How does the diffuse type of tenosynovial giant cell tumor commonly present?
- Commonly knee > hip > ankle > calcaneocuboid joints, pt’s typically complain of pain + locking + recurrent swelling
- As tumor grows joint becomes stiff –> ↓ ROM
- Sometimes a palpable mass can be appreciated
- Aggressive tumors erode into adjacent bones and ST’s
