Joints Flashcards
what are the 2 types of joints and what is characteristic about them
1) synarthroses
- Provide structural integrity
- Allow minimal movement
- Lack joint space
2) synovial:
- freely movable
- Dense fibrous capsule reinforced by ligaments & muscles
what are the 2 types of synarthroses
1) fibrous synarthroses
- syndesmosis
2) Cartilaginous synarthroses
- symphyses(joined by fibrocartilaginous tissue and firm ligaments):
- Synchondrosis(articular cartilage without synovium)
what joints are syndesmosis, symphyses, synchondrosis
Syndesmosis(bones connected by fibrous tissue without cartilage): Cranial sutures, Tibiofibular syndesmosis
Symphyses (joined by fibrocartilaginous tissue and firm ligaments): vertebral bodies
Synchondrosis(articular cartilage without synovium):1st rib and sternum
what are synovial joints AKA
cavitated joints
what are the diff types of synovial joints and give examples
Uniaxial joint
Movement around only one axis= elbow hinge joint
Biaxial joint
Movement around 2 axes=wrist, thumb
Polyaxial joints
Movement in any axis= ball and socket
Plane joint: articular surfaces glide over one another =patella
what are the 2 types of synoviocytes
Type A: macrophage-like synoviocytes
-macrophages with lysosomal enzymes (ability to degrade cartilage)
Type B: FibroBlast-like synoviocytes
-Synthesize hyaluronic acid & proteins (allows for elasticity and fluid)
what does expansion of type B fibroblast like synoviocytes indicate
hallmark of RA
what does the synovium control
- Diffusion in and out of the joint
- Ingestion of debris
- Secretion of hyaluronate, immunoglobulin and lysosomal enzymes
- Lubrication of the joints:
how does the synovium lubricate and nourish the joint
secret glycoproteins
what is the importance of the synovium lacking a basement membrane
allows quick exchange between blood and synovial fluid
what are characteristics of synovial fluid
Clear
Viscous
Filtrate of plasma containing hyaluronic acid
Acts as a lubricant and nourishes chondrocytes of the articular cartilage
what is the importance of collagen, water, proteoglycans, and chondrocytes in hyaline cartilage
Type 2 collagen: tensile strength Water: limits friction Proteoglycans: elasticity Chondrocytes: synthesize matrix -Secrete degradative enzymes in inactive form -Enrich matrix with enzyme inhibitors
what functions as the elastic shock absorber in synovial joints
hyaline cartilage
what is hyaline cartilage AKA
articular cartilage
what does hyaline carilage lack
Lacks blood supply
No lymphatic drainage
No nerve innervation
what is the pathophys of diseases that destroy the articular cartilage
they activate the catabolic enzymes and decrease the production of inhibitor.
what are the different hyaline cartilage zones
1) Tangential or gliding zone: Closest to articular surface
- contains Chondrocytes and Type II collagen
2) Transitional zone
- contains Chondrocytes and Hyaline cartilage
3) Radial zone
- Contains Collagen fibers
4) Calcified zone: Calcified matrix
- Contains immature cells as Cartilage cells regenerated here and migrate upward
what is the Tidemark
separates radial from calcified zone
what are the 2 types of idiopathic (primary) OA
Localized OA: hands, feet, knee, hip, and spine common
Generalized OA: involvement of 3 or more joint sites
what causes secondary OA
Trauma
Congenital or developmental
what are typical OA locations with older compared to younger adults
older= wt bearing joints and fingers younger= joints subject to trauma
why is OA 55 years of age: more common in females
estrogen is protective of bone and joints (although more tears of ligaments occur when estrogen is high)
is there a hereditary predisposition to OA
yes
what is the pathogenesis of primary OA
either 1)damage to normal articular cartilage by physical force or 2)defective cartilage (genetic) fails under normal joint loading =friction is sensed by osteocytes= inc osteoblast function= subchondral bone thickening= nonfunctioning painful joint
how does cracks in articular cartilage cause death of chondrocytes and formation of osteophytes
1-Crack in articular cartilage allows influx of synovial fluid
2-Further loss and degeneration of cartilage
3-Cartilage gradually worn away
4-Below tidemark, new vessels grow in from epiphysis & fibrocartilage deposited
5-Fibrocartilage plug is not mechanically sufficient & can be worn away
6-Exposes subchondral bone plate which becomes thickened
7-If there is a crack, synovial fluid leaks into marrow space producing subchondral bone cyst
8-Focal regrowth of articular surface leads to formation of osteophytes
what are the 3 phases of chondrocyte activitye
1) Chondrocyte injury: related to age, genetic and biochemical factors
2) Early OA: chondrocytes proliferate and secrete inflammatory mediators, collagens, proteoglycans, and proteases=Act to remodel cartilaginous matrix and initiate secondary inflammatory changes
3) Late OA: repetitive injury and chronic inflammation lead to chrondrocyte drop out, marked loss of cartilage and extensive subchondral bone changes.
how are cytokines involved in OA
cytokines (IL-1B, TNF) activate chondrocytes that produce substances (MMP, ADAMTS-4) that destroy cartilage
how is the WNT gene related to OA
WNT= inc B-catenin= inc osteoblast activity= inc bone growth
what is COL2A1 gene
type 2 collagen gene related to OA
what is chondromalacia
Subcategory of osteoarthritis
Patellar surface of femoral condyles
Pain and stiffness of knee
what may X ray show with OA
Narrowing of joint space (from Loss of cartilage)
Increased thickness of subchondral bone
Subchondral bone cysts
Large peripheral growths of bone and cartilage (osteophytes)
what is eburnation
conversion of bone into hard ivory-like mass
what are joint mice
dislodged pieces of cartilage & subchondral bone into the joint
what are osteophytes
bony outgrowths develop at margins of articular surface. Capped by fibrocartilage and hyaline cartilage that ossify
what are heberden nodes
osteophytes at distal interphalangeal joints
what can RA effect
Affect many tissues and organs—mainly joints but also skin, blood vessels, heart, lungs, and muscles
what joints are more likely affected with RA
usually bilaterally in Proximal interphalangeal and metacarpophalangeal joints, elbows, knees, ankles and spine
what is characteristic of synovial fluid from RA
Produces a NONSUPPURATIVE proliferative and inflammatory synovitis
what does RA progress to
Often progresses to destruction of the articular cartilage and ANKYLOSIS of the joints(consolidation of bone).
what is the genetic component of RA
HLA proteins and PTPN22 (Tyrosine phosphatase=activates inflammatory cells(B and T cells))
what is seroposative and seronegative RA? which is better prognosis
Seropositive RA (poor prognosis) High frequency of arginine in the DR epitope
Seronegative RA (good prognosis) High frequency of lysine in the DR epitope
what is the humoral(antibody) component of RA
1)Seroposative-RA has antibodies(IgM RF and either IgG RF or IgA RF), made to HLA-DR4 that bind to the Fc region of other antibodies(IgG) = large structures(IgG RF+IgGFc) that get deposited in joints
2) Seronegative-Abs to citrulline modified peptides (CCP)
- Antibodies to filaggrin with cross reactivity to keratin and perinuclear factor
what is the cellular immunity component of RA
T cell activation with production of TNF and IL-1=Increased vascular permeability and activate macrophages= activates B and T cells even more
what is the infectious agent component of RA
Antibodies against RANA: RA associated nuclear antigen
RANA is related to nuclear antigen encoded by EBV
how are the synovial cells affected by RA
1-Decreased response to glucocorticoids
2-Increased production of hyaluronate
3-Release connective tissue activating peptide which causes increase in prostaglandins (PGE2)
how does RA cause osteoclastogenesis
up regulation of RANKL on T-cells and synoviocytes
what is pannus? what causes it?
a collection of diff cells that accumulate on the joint surface forming a “cloak” formed by Synovia hyperplasia with mast cells=Contains cells which cause cartilage destruction and erosion of subchondral bone(synoviocytes, osteoclasts and inflammatory cells.)
what is produced by pannus? what is its effect
collagenase, PGE2, and IL-1 which stimulate osteoclasts =erodes the articular cartilage and adjacent bone
where does bone loss occur with RA? what does it lead to?
juxta-articular (immediately adjacent to both sides of the joint)
- Pannus penetrates subchondral bone involving tendons and ligaments
- Leads to deformities and instabilities
- Joint undergoes fibrous fusion: ankylosis
- Long standing cases develop bony bridging: bony ankylosis
RA typically starts in the fingers. Where does it progress to?
HANDS to WRIST to ELBOWS
what are rheumatoid nodules? what are they composed of
Movable firm, rubbery and occasionally tender nodles composed of Central core of fibrinoid necrosis and a Rim of macrophages surrounded by lymphocytes, plasma cells
where are rheumatoid nodules found
found in areas of pressure (ie elbows)
may also be found in vessels causing necrotizing vasculitis
what are the s/sx of RA
Symmetrical Small joints affected before larger one Swollen, warm, painful Stiff on arising or following inactivity Limitation of motion Malaise Fatigue
what will Xray show with RA
Joint effusions
Juxta-articular osteopenia
Erosions and narrowing of joint space
Loss of articular cartilage
how do you diagnose RA
4 of the following
MORNING STIFFNESS, MEAN AGE 45 YRS ARTHRITIS in MORE THAN 3 JOINT AREAS “TYPICAL” hand findings, MP ULNAR deviation SYMMETRIC ARTHRITIS SERUM RHEUMATOID FACTOR “TYPICAL” X-RAY findings Rheumatoid nodules
what is abatacept
T cell modifier to tx RA
what is rituximab
blocks B cells to tx RA
what is anakinra
anti IL-1 to tx RA
what is tocilizumab
anti IL-6R to tx RA
what are etanercept, infliximab, and adalimumab
anti TNF alpha
what is the criteria for Juvenile idiopathic arthritis
1-All forms of arthritis that develop before 16 years of age &
2-Persist for a minimum of 6 weeks
what are the similarities between RA and JIA
Genetic: HLA
Environmental
Inflammatory synovitis and morphologic changes
Abnormal immunoregulation
what are the diff between RA and JIA
In JIA
- oligoarthritis(4 or more joints) is more common
- Systemic disease is more frequent
- Large joints greater than small joints
- Rh nodule and Rh factor are usually absent
- ANA seopositivity is common
what is Pauci
2-4 joints effected
are spondyloarthropathies seroposative or seroneg
seroneg
what is ankylosing spondylitis? what causes it? what is it AKA
fusion of joints caused by HLA-B27
AKA “rheumatoid” spondylitis, or Marie-Strumpell Disease
what are spondyloarthropathies
ankylosing spondylitis and reactive arthritis
what is the involvement of spondyloarthropathies
joints: Asymmetric involvement of only a few peripheral joints
Tendency to inflammation of periarticualr tendons and fascia
Systemic involvement of other organs: uveitis, carditis, and aortitis
what is the T cell response with spondloarthropathies
initiated against unidentified antigen(infectious agent) that cross reacts with native molecules of M/S system
what joints are typically affected with ankylosing spondylitis
Chronic inflammatory arthropathy that starts at sacroiliac joints joints and works its way up the vertebral column.=spine fuses
May accompany asymmetric peripheral arthritis and systemic manifestations
who typically gets ankylosing spondylitis
almost exclusively in young men
90% have HLA-B27
what is reactive arthritis AKA
Reiter syndrome
what is the reiter syndrome triad
Seronegative polyarthritis
Conjunctivitis/uveitis
Nonspecific urethritis(nongonococcal) or cervicitis
what is reiter syndrome associated with
follows venereal exposure or episode of bacillary dysentery= common in HIV+
what joints are most commonly effected from reiter syndrome
ankles, knees, and feet most common but severe chronic dz affects the spine resembling ankylosing spondylitis
what is the pattern of symptoms from reiters
episodes come and go over weeks to 6 months
besides reiters, what is the other type of “reactive” arthritis
Enteritis-Associated Arthritis
what are the two types of causes of Enteritis-Associated Arthritis
1)GI infection:salmonella, shigella, campylobactor
Contain lipopolysaccharides as a major component
2)Ulcerative colitis and crohn disease
what is the pattern of symptoms of GI inf causing Enteritis-Associated Arthritis
Last approximate 1 year, then clears
does resection of the affected bowel in UC and crohns relieve the arthritis in Enteritis-Associated Arthritis
only in UC, not in chrons
what joints are affected in Enteritis-Associated Arthritis
Knees and ankles most common
Can affect wrists, fingers, and toes
does enteritits associated arthritis cause ankylosing spondylitis
only rarely
what is HLA-B27 linked to
psoriatic SPONDYLITIS and inflammation of distal interphalangeal joints
what is HLA-DR4 associated with
rheumatoid pattern of involvement of Psoriatic arthritis
what joints are typically affected by psoriatic arthritis
Affects peripheral and axial joints
Can also have conjunctivitis and iritis
how does the severity of psoriatic arthritis compare to RA
Not as severe as RA but remissions more frequent
what is infectious arthritis from
osteomyelitis (USUALLY SUPPURATIVE
GC, staph, strep, H. flu, E. coli, (Salmonella in sicklers))
what are the 4 cardinal signs of infectious arthritis
fever, leukocytosis, ESR, pain
what joints are affected most in infectious arthritis
knee, hip, shoulder, elbow, wrist then sternoclavicular joints
what joints are more commonly affected from infectious arthritis in drug addicts
axial articulations (bones along the central axis)
how quickly does TB cause infectious arthritis
insidious onset since TB is a slow growing organism
what does infectious arthritis from TB form
Forms confluent granulomas with central caseousnecrosis
what is characteristic of joint involvement from LYME dz infectious arthritis
remitting and migratory
usually large joints: knee
why does LYME dz cause infectious arthritis
HLA-DR molecules bind an epitope of the borrelia which initiates a T-cell reaction
what might silver stains reveal with LYME dz infectious arthritis
a small number of organisms
what viral organisms can cause infectious arthritis
Parvovirus B19
Rubella
Hepatitis C
what is primary and secondary gout
primary: hyperuricemia present w/o other dz
secondary: other dz present(often in fast growing malignancies)
does hyperuricemia always cause gout
no, 10% of population has hyperuricemia (>7 mg/dl), but only 1/20 of these has gout
what can cause increase in uric acid
Overproduction Increased catabolism of nucleic acids Greater cell turnover Decreased salvage of free purine bases Decreased urinary uric acid excretion (most cases of primary gout)
how are thiazides related to gout
Thiazides reduce excretion of urate (switch to a diff diuretic if gout s/sx begin)
what is Probenecid
drug that inc uric acid excretion to tx gout
what is Apo-E coating
inhibit Ab response to gout crystals
how long after hyperuricemia will gout sx typically begin
Gout rarely appears before 20 to 30 years of hyperuricemia
what occurs with mutated HGPRT
hypoxanthine transferase involved in the salvage pathway of free purine bases. A mutation inc risk for gout
besides age and genetics, what factors inc risk for gout
ETOH abuse, Lead toxicity, obesity,drugs (thiazides)
what are the manifestations of gout
TOPHACEOUS ARTHRITIS
-Tophi: large aggregates of urate crystals
GOUTY NEPHROPATHY
-Urate nephropathy
what is the pathology of gout
- Sodium urate crystals precipitate from supersaturated body fluids
- Precipitated crystals absorb fibronectin, complement and other proteins on their surfaces.
- Neutrophils that have ingested urate crystals release activated oxygen species and lysosomal enzymes: mediate tissue injury and promote an inflammatory response
- Cells die releasing crystals stimulating further inflammatory reaction
- Extracelular soft tissue deposit of urate crystals surrounded by foreign body giant cells(macrophages): TROPHUS
what is the spiral of gout
attack starts= crystals form= WBC attack= crystals “pop” the cell= cell releases proteins= proteins call in more WBC and cause inflamm/pain and proteins lower pH making it possible for more crystals to form
what are Xray findings with gout
Punched out juxta articular lytic lesions (Rat bite)
Minimal reactive new bone
what is the course of gout dz
1)Asymptomatic hyperuricemia: precedes clinical manifestations
-Can last years
2)Acute gouty arthritis: Painful
Involves one joint: later in course of disease is polyarticular
>50% have podagra: painful redened big toe (metatarsophalageal)
Fever
3)Intercritical period
Asymptomatic interval between initial acute attack and subsequent episodes: Can last 10 years
4)Tophaceous gout
Appearance in cartilage, synovial membranes, tendons, and soft tissues.
what is podagra
painful redened big toe (metatarsophalageal) form gout
what are the renal manifestations of gout
1)Renal failure
Responsible for 10% of deaths in persons with gout
2)1/3rd have mild albuminuria, reduced GFR & decreased renal concentrating ability
3)Urate Stones
10% of all renal calculi in US are urate stones
Urate stones correlates with serum concentatriton of uric acid
Also have increased freuqency of calcium containing stones (uric acid may serve as a nidus)
what other diseases is gout associated with
1) Atherosclerosis
2) HTN
what is diff bt gout and pseudogout
Gout: Monosodium Urate
-younger
Pseudo-GOUT: Calcium Pyrophosphate
-“condition of old age”
what is pseudogout AKA
CHONDROCALCINOSIS, or CPPD (Calcium Phosphate Deposition Disease)
what does secondary pseudogout result from
joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism, ochronosis, and diabetes
