Joint Pathology Flashcards
What type of collagen makes up articular cartilage? Which type of nerve innervates it?
- type II collagen
- lacks nerve endings! (therefore pathology of just the articular cartilage will not be painful)
What is degenerative joint disease? What are the three main risk factors? Is it mainly systemic or localized?
- osteoarthritis
- progressive deterioration of articular cartilage due to wear and tear
- risk factors: old age, obesity, trauma
- not entirely systemic; usually affects hip, lumbar spine, knees, and the DIP and PIP joints of fingers
How do patients with degenerative joint disease typically present? What are some complications?
- patients are usually 65+ and complain of joint stiffness in the morning that WORSENS and becomes painful during the day with use
- (joint stiffness that improves with use indicates rheumatoid arthritis)
- when the cartilage wears away and bone rubs against bone, we get eburnation (polishing) of the subchondral bone and osteophyte (bony outgrowth/swelling) formation
What is rheumatoid arthritis? What is the hallmark feature of this disease? Is it mainly systemic or localized?
- a chronic, systemic autoimmune disease
- hallmark: synovitis, resulting in pannus formation (inflamed granulation tissue)
- although systemic, it mainly affects the wrists, elbows, ankles, knees, PIP and MCP joints of fingers (bilateral, symmetrical involvement)
- the DIPs are usually spared
How do patients with rheumatoid arthritis typically present?
- patients are usually between 40 and 60 and complain of symmetrical joint stiffness in the morning that IMPROVES with activity
- (movement squeezes the inflammatory debris out of the joint, relieving some of the pressure and pain)
- (joint stiffness that worsens as the day goes on indicates degenerative joint disease)
- systemic symptoms also present (fever, malaise, etc.)
What are some symptoms and complications of rheumatoid arthritis?
- ankylosis (fusion) of the affected joints, osteopenia, baker cyst, vasculitis, fever, malaise, weight loss (don’t forget it’s a systemic disease)
- complications: anemia and secondary amyloidosis
- the ankylosis is due to the contracting nature of the myofibrils present in the pannus/inflamed granulation tissue
What would you expect to find in the serum of a patient with rheumatoid arthritis? In the synovial fluid?
- serum: IgM and IgA antibodies against the Fc portion of IgG (this is called rheumatoid factor) + anti-cyclic citrullinated peptide antibodies (anti-CCPs, ACPAs)
- 50-80% of patients will have one or the other or both
- (anti-CCPs are more specific than RF for RA)
- synovial fluid: large amounts of neutrophils and proteins
What percentage of rheumatoid arthritis risk is associated with genetics? Which specific gene?
- about 50% is due to genetics
- HLA-DR4
- (there is a shared epitope in patients with RA at HLA-DR beta 1 at residues 70-74, with a positively charged residue at 71)
What is seronegative spondyloarthropathy? Which gene is is associated with? What are the three major types?
- diseases that affect the axial skeleton and sacroiliac joints (“spondylo”) and that lack rheumatoid factor (hence the seronegative)
- associated with HLA-B27
- an “auto-inflammatory” disease rather than an auto-immune one
- ankylosing spondyloarthritis, Reitier syndrome (reactive arthritis), and psoriatic arthritis (also, colitic arthritis and acute anterior uveitis)
Which joints are usually involved in ankylosing spondyloarthritis? What happens to these joints over time? What can patients present with?
- (a type of seronegative spondlyoarthropathy)
- involves the sacroiliac joints and spine
- the vertebrae fuse over time (ankylosis), giving rise to “bamboo spine”
- patients may present with lower back pain, unilateral uveitis, enthesitis, and aortitis (aortitis can increase the risk of aneurysm; an aneurysm at this location increases the risk for aortic regurgitation)
What is Reiter syndrome? When is classically seen?
- (a type of seronegative spondlyoarthropathy)
- a combo of arthritis, urethritis, and conjunctivitis (“can’t see, can’t pee, can’t climb a tree”)
- classically arises in young male adults after a GIT (Campylobacter jejuni, salmonella, shigella, etc.) or chlamydia (C. trachomatis) infection
- AKA ‘reactive arthritis’
- can be due to an inflammatory reaction in response to infection at a distant site (so the organism is actually in the joint)
What is psoriatic arthritis? What is the most severe form known as?
- (a type of seronegative spondlyoarthropathy)
- arthritis of axial and peripheral joints, especially the DIP joints (results in nail changes, very common) and feet
- this is a complication of psoriasis (10% of cases)
- most severe and progressive form is arthritis mutilans
What is the most common agent of infectious arthritis in infants? In children? adults?
- infants and very young children: S. aureus, group B strep, H. influenzae
- young adults: N. gonorrhoeae (most common), S. aureus
- older adults: S. aureus
- (the agent is usually bacterial; S.aureus is the most common cause; septic arthritis)
- usually due to hematogenous or traumatic route
How do patients with infectious arthritis typically present?
- with a warm, erythematous painful joint that is limited in motion (onset is sudden)
- (usually involves a single joint - 90% of cases involve the knee)
- systemic signs of infection may also be present (fever, increased WBC, increased ESR)
What is gout? What is it due to? Which joint is most commonly affected?
- deposition of MSU (monosodium urate) crystals in tissues (especially in the joints)
- due to hyperuricemia (elevated uric acid levels)
- very commonly affects the podagra (the MTP joint of the big toe)
Where does uric acid come from? What usually happens to it? Using this information, what can cause hyperuricemia?
- uric acid comes from the metabolism of purines (AMP + GMP) that are digested from eaten DNA and RNA
- uric acid usually leaves the enterocyte, enters the blood, and is excreted by the kidneys
- hyperuricemia can therefore be caused by excess uric acid production from the diet or from a failure of renal excretion of the uric acid
Which is more common, primary or secondary gout? What causes both?
- primary gout is more common; 90% are due to underexcretion of uric acid, 10% due to overproduction of uric acid
- secondary gout can be due to leukemia and a myeloproliferative disorder (both of these result in increased cell turnover), Lesch-Nyhan syndrome (missing an enzyme involved in purine/uric acid metabolism), or renal insufficiency
- gout is more common in males
What happens in an acute case of gout? What can develop in a chronic case?
- acute: MSU (monosodium urate) crystals active neutrophils to trigger acute inflammation = painful arthritis
- in chronic gout, tophi can develop (these are firm, subcutaneous deposits of urate), as can renal failure (the uric acid deposits in the tubules and damages them)
What do we see in the serum of a patient with gout? In the synovial fluid?
- serum: hyperuricemia
- synovial fluid: needle-like crystals with a NEGATIVE birefringence under polarized light (crystals parallel with the light appear yellow, those perpendicular appear blue)
- (under paraLLel light, MSU crystals will be yeLLow)
What is pseudogout? What do we see in the synovial fluid of a patient with pseudogout?
- clinically identical to gout, but due to calcium pyrophosphate dihydrate (CPPD) crystal deposition
- synovial fluid: rod or square or rhombus-like crystals with weak POSITIVE birefringence under polarized light (crystals parallel with the light appear blue, those perpendicular appear yellow)
What are some risk factors of infectious arthritis?
- prosthetic joints, skin infection, joint surgery, rheumatoid arthritis, diabetes mellitus
What is the principal site of seronegative spondyloarthropathy? (ie what part of the joint is affected?)
- the enthesis (where tendons and ligaments join the bone)
- enthesitis (most common sites are the Achilles’ tendons and the plantar fascia)
What are the four stages of gout?
- asymptomatic hyperuricemia –> acute gouty arthritis (sudden, excruciating pain; 50% of cases involve the big toe) –> intercritical period (asymptomatic period, possibly with recurrent attacks) –> chronic tohpaceous gout
- in chronic form, deposits in the ear lobe are quite common
What is the causative agent of Lyme disease? What are the three stages of the disease? What are four major and common effects/complications?
- caused by the spirochete Borrelin burgdorferi, which is transmitted by deer ticks
- stage 1: multiplication of spirochetes at the site of tick bite; erythema chronicum migrans (expanding area of redness), fever, lymphadenopathy
- stage 2: early disseminated stage; hematogenous spread results in skin lesions, lymphadenopathy, migratory joint pain and muscle pain, cardiac arrhythmia, meningitis (IgM and IgG appear now)
- stage 3: late disseminated stage (2-3 years after the bite); chronic arthritis of the large joints, encephalopathy
- major complications: bilateral facial nerve palsy, arthritis, cardiac block, erythema migrans
What is the classic patient with ankylosing spondylitis? Why has it been so under-diagnosed?
- classic patient is male less than 45 years of age (rare for older patients) complaining of back and/or buttock pain lasting longer than 3 months
- under-diagnosed because X-rays show no signs of disease at early stage (use MRI instead!), the symptoms are commonly misdiagnosed as general back pain, and because there is a diagnostic delay of 8 to 11 years
What percentage of patients with ankylosing spondylitis have HLA-B27? What percentage of patients with HLA-B27 have ankylosing spondylitis? What percentage of patients with other spondlyoarthropathies have HLA-B27?
- 90% of patients with AS have HLA-B27, but only 5% of patients with HLA-B27 have AS
- 50% of patients with psoriatic arthritis have HLA-B27
- 50% of patients with colitic arthritis have HLA-B27
- 10-60% of patients with reactive arthritis have HLA-B27
What are the chances a relative of someone with ankylosing spondylitis developing the disease?
- identical twin: 65%
- sibling, parent, child: 8%
- cousin: 1%
Arthritic nodes of the DIP are known as _______; arthritic nodes of the PIP are known as ________. What diseases are these seen in?
- DIP: Heberden nodes
- PIP: Bouchard nodes
- osteoarthritis has both; rheumatoid arthritis has only PIP (Bouchard nodes)
- DIP involvement is also very common in psoriatic arthritis
Other than TNF-alpha, what other inflammatory agents are associated with ankylosing spondylitis?
- IL-17 and IL-23
What four things do we use to diagnose rheumatoid arthritis?
- joint involvement (usually symmetrical, commonly involves the ankles, knees, elbows, wrists, PIPs and MCPs)
- serology (rheumatoid factor, ACPA/anti-CCP)
- acute phase reactants (ESR and CRP)
- duration of symptoms
What is pseudogout associated with?
- hyperparathyroidism and hemochromatosis
Compare the synovial fluid in a normal patient, a patient with RA, a patient with gout, and in a patient with septic arthritis.
- normal: clear, highly viscous, WBC less than 200
- RA or gout: variable transparency, yellow, decreased viscosity, increased WBC (between 2,000 - 20,000)
- septic: opaque, variable viscosity, very increased WBC (25,000 - 100,000)
