Pathology Of Mono/polyarthropathies Flashcards
Joint classifications
Solid (nonsynovial)
Cavitation (synovial)
Synovial membrane contents
Lined with type A synoviocytes at surface of joint
(Specialized macrophages
Lined with type B synoviocytes underneath A synovicoytes
(Synthesize hyaluronic acid and proteins)
Chondrocytes
Synthesis ECM and enzymatically digest it based on signals.
Osteoarthritis (OA)
Also called degenerative joint disease
Charcterized by degeneration of cartilage in synovial joints
MOST common disease of joints
Prevalence increases exponentially once age 50. Usually 40% if 70+
Usually has no underlying initiating cause other than gaining
- primary OA
Can be secondary OA when due to trauma or joint deformity.
Pathogenesis of OA
Lesions of OA stem from degeneration of the cartilage and its disordered repair.
ECM disorder Caused by REPEATED biochemical stressors and genetic factors
- collagen/cartilage degradation exceeds synthesis in chondrocytes.
Late stage = chondrocytes number loss and severely degraded ECM
Matrix mealloprotienases
Produced by chondrocytes to degrade collagen type 2 cartilage
Commonly involved joints in OA in decreasing order
Hips
Knees
Lower lumbar and cervical vertebrae
Distal IP joints
Metacarpal and metatarsal joints
Heberden nodes
Osteophyte growth at the distal interphalangeal joints
Found in OA
Symptoms and characteristics of OA clinically
Joint pain that worsens with use, morning stiffness. Not bilateral and usually asymmetrical
Can impinge on spinal foramina by osteophytes results in cervical and lumbar nerve root compression.
Rheumatoid arthritis general characteristics
Chronic inflammatory joint pain that is autoimmune origin.
Causes proliferative inflammatory synovitis
Often progresses to destruction of articular cartilage and can cause ankylosis (adhesion/fusion of joints)
More common in women than men
- also more common in 30s-50s
Almost purely genetic and environmental based
Pathogenesis of RA
50% of risk is inheriting genetics - specifically the HLA class 2 locus
Infection (specifically periodontitis) and smoking can cause new epitopes forming which promotes autoimmune action via citrullination of self-proteins.
CD4 Tcells initiate the autoimmune response
Synovium of RA joints include plasma cells that produce antibodies in the synovium to the citrulinated proteins
Specific cytokines that play in RA
IFN-y = activates macrophages in the in the type A synoviocytes degrade cartilage
IL-17 = recruiters neutrophils and monocytes to the area
RANKL = stimulates osteoclasts and bone resorption
TNF and IL-1: overstimulate macrophages to secretary’s proteases that destroy hyaline cartilage
Auto antibodies and citrullinated protiens
Antibodies in the synovium react to citrullinated proteins produced in the beginning stages of RA.
Produces complexes of autoantibodies and proteins in the joints which causes inflammation
Rheumatoid factor
Most common pathogenesis of RA.
80% of RA patients have serum antibodies that bind to self IgG Fc regions.
DOESNOT necessarily indicate RA, but RA patients do have high rheumatoid factor
Symptoms and clinical charcterisitcs of RA
Symmetric arthritis
Pain bouts last for long time (1 hour+)
Usually affects small joints
Can cause fibrous ankylosis and bony ankylosis via pannus bridging of the bones of the joint if left untreated.
- anticitrullinated protein antibodies ALWAYS mark RA
- symptoms include malaise, fatigue and pain that grows progressively worse
Radiographic findings show joint effusions and osteopenia with erosions/ loss of cartilage
Rheumatoid nodules
Infrequent manifestations of RA but occur in subcutaneous tissues in forearm elbow and occiput
Resemble necrotizing granulomas
Seronegative spondyloarthropathies
Heterogenous group of disorders
All share the following characteristics:
- Absence of rheumatoid factor
- ligamentous attachments pathogical changes, not synovium.
- associated with HLA-B27 gene impairments
- leads to ankylosis
- usually involves in sacroiliac joints if joint issues
- are immmune mediated and triggered by T-cells that cross-react with self-antigens on bones and ligaments.
Ankylosis spondylitis
Prototypical spondyloarthropathy
Directly affects peripheral joints and spine and appears bamboo like in the spine.
90% of all patients are HLA-B27 positive
Anti IL-17 antibody can treat it
Reactive arthritis
“Triad of arthitis”
- nongonococcal urethritis
- cervicitis
- conjunctivitis
- HLA-B27 positive and tends to affect men in their 20-30s
- Hypothesized to be autoimmune related, initially caused by a GI or GU infection
- Ankles, feet and knees are most commonly affected and show an asymmetric pattern
- can be indistinguishable from ankylosis spondylitis if severe.
Psoriatic arthritis
Chronic inflammatory arthropathy marked with psoriasis affecting peripheral and axial joints ligaments and tendons.
Affects both sexes equally at ages 30-50
Can be a secondary disease to psoriasis but usually isn’t
HLA-B27 and HLA-Cw6 genes affected
Most common site is distal interphalngeal joints producing a “pencil in the cup” appearance radiographically
Calcium pyrophosphate crystal deposition disease (Pseudogout)
Also known as CPPD
Has 3 types, sporadic, hereditary and secondary
- autosomal dominant variant is hereditary through germline
Caused by degradation of articular cartilage proteoglycans, allowing crystals to form around chondrocytes
- usually found in 50 years plus
- associated with hyper parathyroidism
Gout
1st crystal induced arthritis introduced
- crystals are monosodium urate crystals in joints and surrounding soft tissues during acute arthritis attacks
Can be primary or secondary (cause unknown)
Joint mice, fibrous-walled cysts and bone eburnation
Found in OA especially late stages
Joint mice = dislodged pieces of cartilage or bone that break off and tumble around in the joint
Bone eburnation: polished ivory appearance of bone caused by direct subchondral bone rubbing together
Fibrous walled-cysts: small fractures that have forced synovial fluid within them
Usual treatment of OA
NSAIDs
Intra articular corticosteroids (if permitted)
Arthroplasty if severe
Educate the patient for good health habits
Citrullination of proteins
AA arginine is converted into citrulline. (Turns polar into non polar so less functional protein)
- immune system does not recognize this as self and attacks it.
- catalyzed by arginine deiminases.
Pannus
A mass of edematous synovium, inflammatory cells, granulation tissue and fibroblasts that grow over the articular cartilage and causes erosion of the cartilage
If untreated, can cause ankylosis by “bridging” the bones in the joint.
Found in RA
Treatment of RA
Corticosteroids
Methotrexate
TNF antagonists
TNF is most effective cytokine to treatment against for RA
Gout pathogenesis
Hyperuricemia (above 6.8mg/dL plasma urate) is necessary, but does not definitively prove gout.
Hypothesized to include abnormal purine production since purine catabolism produces Uric acid
- repeated acute arthritis attacks leads to TOPHI formation (aggregates of urate crystals and inflamed tissue)
- can form pannus as well if not treated.
Primary vs secondary gout
Primary gout: elevated uric acid levels caused by decreased excretion which is unknown as to why.
Secondary gout: increased production of purine or decreased excretion.
- increased production is caused by rapid cell lysis and tumor lysis syndrome
Factors that lead to gout
Genetic predisposition
Alcohol consumption
High BMI
High fructose levels
Being male
Possessing metabolic syndrome or having renal failure past/present.
4 clinical stages of Gout
Asymptomatic hyperuricemia: usually around puberty and after menopause
Acute arthritis: several years after asymptomatic
- marked by sudden excruciating joint pain, localized hyperemia and warmth
Asymptomatic intercritical period: after resolution of acute arthritis
- marked by symptom free interval w/ occasional mild flare ups that are polyarticular
Chronic tophaceous Gout: 12 years after acute arthritis
- forms tophi
Most common place for acute gout
1st metatarsal forms podagra
Gout treatment
Lifestyle modifications
Xanthine oxidase inhibitors are 1st line in chronic only
NSAIDs are first line in acute only
CCPD pathogenesis
Unknown
- however is suggested that articular cartilage proteoglycans are degraded which always for pyrophosphate crystals to form.
- usually appears 1st in IVDs and meniscus (articular cartilage)
- usually less inflammation than gout
- likely in patients with chondrocalcinosis appearance
CCPD morphology
Oval blue-purple aggregates
- individual crystals appear rhomboid shaped and are blue due to positive birefringent properties
Clinical course of CCPD
Usually asymptomatic at first
- can produce acute or chronic arthritis if left untreated
- can be mono or polyarticular
- 50% of all infected will experience significant joint damage at some point
- no treatment to slow disease progression
Etiology of septic arthritis
Hematogenous spread
Extension of localized ST infections
Direct introduction to pathogen via trauma
Most common agents for septic arthritis
Staph Aureus is the most common agent for non-Gonoccal
Strep pneumoniae and B-hemolytic step are next
*gonorrhoeae is the most common in sexually active patients and Gonoccal form
Risk factors for developing septic joints
Prosthetics
Unprotected sex
RA
+ 80 yrs of age
Have diabetes
IV drug abuse
Levels of white blood cells with respect to synovialjoint issues
Non inflammatory = 0-2000 mg/dL
- OA, traumatic arthritis, CCPD
Inflammatory = 2000mg/dL
- RA, seronegative polyarthropathies
Septic = 20,000 mg/dL
- septic arthritis
