Osteoarthritis & Gout Flashcards
What does osteoarthritis mean?
“osteo” –> bone
“arthritis” –> inflammation of joint
What is the definition of osteoarthritis (OA)?
Osteoarthritis (OA) is a CHRONIC JOINT disease that leads to DESTRUCTION and IMMOBILITY of joints
- It occurs when the protective cartilage that cushions
the ends of bones wears down over time
- Other names: “osteoarthrosis” and “degenerative joint disease”
There are two types of OA:
- Primary (idiopathic)
- MOST common form of disease
- no predisposing factor is apparent
- Secondary
- pathologically is not distinguishable from primary - has a known underlying cause
What is the epidemiology of OA?
- OA is the MOST COMMON type of joint disease
- Joint distribution of OA in males and females <55 years is similar
- In patients >55 years:
- hip OA is more common in males
- OA of hands, thumb base, and knee are more
common in females - The prevalence and pattern of involved joints vary in different races (genetic? life-style?) - may play a role
Joint distribution of OA in males and females <55 years is ____
similar
In patients >55 years:
- hip OA is more common in MALES
- OA of hands, thumb base, and knee are more
common in FEMALES
What are the risk factors for OA?
- AGE
- female sex
- race
- genetic factors
- JOINT INJURIES (sport, accident)
- repeated stress (job, sport)
- OBESITY
- congenital developmental defects
- prior inflammatory joint disease (infectious/non-infectious)
- metabolic & endocrine disorders (diabetes, hemochromatosis - condition where body has overload of iron & can lead to bone damage overtime)
- Typically a combination of loading and susceptibility (local, systemic) risk factors is required to cause disease or its progression. (*look at slide 7)
Describe how obesity is a risk factor for OA?
2 reasons (directly & indirectly):
1. ↑stress to weight-bearing joints (hips, knees)
2. fat (cells) produces proteins that cause inflammation
____ is the most important risk factor for OA
AGE
What are the joints most often affected by OA?
- Neck (cervical segment of spine)
- Low back (lumbar segment of spine)
- Hips
- Base of thumbs
- Ends of fingers (*proximal & distal interphalangeal)
*middle in RA - Knees
- Base of big toe
OA usually affects the joints in a _____ manner
non-symmetric
*opp. in RA
OA most often affects…
hands, knees, hips, & SPINE
*spine not involved in RA
What does a healthy joint look like?
The ends of bones are encased in smooth cartilage that are protected by joint capsule lined with synovial membrane and fluid
What does Osteoarthritis look like?
The cartilage becomes worn away, spurs grow out from the edge of bone (causes stress to surrounding tissue), synovial fluid increases, and joint becomes stiff and sore
Describe OA of knees:
- more common in FEMALES than males
- may affect 1 or both knees
INCREASED subchondral bone DENSITY (NARROWING of joint SPACE)
*- i.e. more bone (whereas in RA there is decreased density)
Describe OA of hips:
- affects both males & females (more common in MALES)
- may affect 1 or both hips
Joint SPACE is NARROWED, subchondral sclerosis with scattered oval radiolucent cysts, peripheral osteophyte lipping
Describe OA of the hands:
- mainly affects FEMALES
- most often affects the BASE of thumb and joints at the end of fingers
Severe osteoarthritis & osteopenia of carpal joint & 1st carpometacarpal joint
(space has sign. narrowed)
Bouchard’s nodes
Heberden’s nodes
Bouchard’s nodes
formation of hard knobs at MIDDLE finger joints
Heberden’s nodes
formation of hard knobs at FARTHEST finger joints
OA of the neck and back (spondylosis):
- most common type of arthritis in spine
- can occur anywhere in spine but is more common in lower back and neck
- may cause no problem (not complaining about pain)
- pain and stiffness are most common symptoms
Describe OA of the foot:
- generally affects the joint at the base of big toe
Comparison of morphologic features of RA and OA
RA:
- damage to cartilage/bone –> abnormal bone growth
- pannus formation (irreversible)
- inflammation in joint & surrounding
OA:
- bony spurs
- subchondral cyst - loss of bone
- osteophyte - high density of bone
Pathologic changes of joint in OA include:
- surface of joint is damaged (cartilage)
- surrounding bone grows thicker
- leading to joint damage and immobility
The main pathologic feature of OA is progressive loss of articular cartilage but it also involves other tissues:
- subcondral bone
- synovium
- ligaments
- neuromuscular tissues
(damage to cartilage is major but also surrounding area)
The important articular changes in OA:
- EARLY STAGE:
- cartilage is thicker than normal (b/c tries to compensate)
- PROGRESSION OF DISEASE:
- joint surface is breached, vertical clefts (fibrillation) - cartilage is metabolically active
- chondrocytes replicate and form clusters
- LATE STAGE:
- cartilage becomes hypocellular (reduction in # of cells)
- BONE REMODELING AND HYPERTROPHY:
- appositional bone growth occurs in subchondrial region leading to bony “sclerosis” (irreversible & interfers in mobility)
Extracellular matrix of a normal cartilage is composed of:
- Proteoglycans (PGs)
- Collagen
- Matrix metalloproteinases (MMPs)
Proteoglycans (PGs)
which are responsible for the compressive stiffness of the tissue and its ability to withstand load
Collagen
which provides tensile strength and resistance to shear
Matrix metalloproteinases (MMPs)
which can degrade all extracellular matrix components.
The primary changes in OA begin in the ____
cartilage
MMPs appear to have an important role in…
the loss of
cartilage matrix in OA
Synthesis and secretion of ____ might be STIMULATED by IL-1 or by other factors (e.g. MECHANICAL stimuli)
MMPS
What are the signs and symptoms of OA?
- Pain
- Stiffness of involved join
- Localized tenderness, bone or soft tissue swelling (arthritis)
- b/c of ongoing inflammation of the joint
- Bone crepitus (sensation of bone rubbing against bone)
- (*specific to OA)
- can hear it
- Warmth
- Deformation of involved joints
- Marked loss of joint motion
Describe what the pain is like in OA
- DEEP PAIN localized to the involved joint
- usually AGGRAVATED by joint USE and RELIEVED by REST (*diff b/t OA & RA)
- nocturnal pain interferes with sleep and is observed
particularly in advanced OA of hip
Describe what the stiffness of involved joint is like in OA
- mainly after a period of inactivity
- usually lasts <20 minutes
What are the causes of joint pain in patients with OA?
ARTICULAR CARTILAGE is ANEURAL so joint pain in OA patients must arise from other structures (i.e. surrounding tissue)
-*had no nerves therefore doesn’t cause any pain
source –> mech
- synovium –> inflammation
- subchondral bone –> microfractures
- osteophyte –> stretching of periosteal nerve endings
- ligaments –> stretch
- joint capsule –> inflammation
- muscle –> spasm
Diagnostic tests for OA?
- Diagnosis of OA is usually based on clinical symptoms and radiographic features (like RA for ex)
- There is NO correlation between radiographic findings and severity of disease
- sometimes find it on X-Ray but the patient isn’t feeling it that extreme & vice versa
What are Radiographic findings of OA?
- at early stages X-Ray is usually normal
- changes in radiograph become evident as articular cartilage is lost
Main findings of OA in X-Ray include:
- narrowing of joint space
- subchondral bone sclerosis (thickening of bone)
- more bone formation - subchondral cysts
- osteophytosis (bone spurs)
*helpful but not specific to OA
Laboratory tests?
** NO specific lab test is available for diagnosis of OA
- Lab findings may help to identify the underlying cause of secondary OA
- OA is usually not systemic so the lab tests such as ESR CBC, urine analysis are usually normal
- Synovial fluid reveals mild leukocytosis (mainly mono- nuclear cells)
- but non-specific/not helpful
BUT
- Synovial fluid analysis is particularly important for excluding other conditions (gout, septic arthritis, RA)
What are treatment goals for OA?
Treatment of OA is aimed at reducing PAIN, maintaining MOBILITY, and minimizing DISABILITY
What are therapeutic strategies used for OA?
- weight loss
- MILD exercise - not too much b/c joints don’t have as much structure
- NSAIDS
- analgesics
- glucocorticoids (intra- and periarticular injections
not systemic) - surgery (replacement of joint)
What is Hyperuricemia & Gout?
- Gout is a METABOLIC disease caused by precipitation of MONOSODIUM URATE within and around joints
- Gout is a common CRYSTAL-INDUCED arthritis
- URIC ACID is the final product of breakdown of PURINE
NUCLEOSIDES - Uric acid has LOW SOLUBILITY and forms CRYSTALS in higher concentrations
- anything that lowers solubility, pertentriates crystals
Describe Uric Acid Synthesis & Excretion
- Uric acid (UA) synthesis is end product of purine catabolism
Main points:
* UA is filtered from blood by glomerulus and almost completely resorbed by proximal tubules of kidney
- A small fraction of resorbed UA is secreted by distal nephron and excreted in urine
(urate is the form that precipitates in the joints)
What is the epidemiology of gout?
- Gout is more often in men (male:female ratio is about 5:1)
- It is more common in middle age and older men (peak age is 30-50 years)
- Women generally develop signs and symptoms after
menopause - Prevalence of gout worldwide ranges from 0.1-10%
- ASYMPTOMATIC HYPERURICEMIA: 5-8% of population
- elevated blood glucose levels of acid (overtime it starts to precipitate & leads to GOUT)
- Both genetic and environmental factors contribute to development of gout
The most common affected joints in gout are…
fingers, first toes, ankles, knees, and hips
Gout is divided into primary and secondary forms:
- In PRIMARY form (90% of cases), gout is the major manifestation of disease and the CAUSE is usually UNKNOWN.
- In SECONDARY gout (10% of cases), uric acid level is increased because of a KNOWN underlying DISEASE that usually dominates the clinical picture.
Elevated uric acid results from…
increased production, or reduced excretion or both
What are the 3 factors that contribute to Elevated Uric Acid?
- Increased uric acid production
- inherited enzyme deficiencies
- myeloprolifrative disorders (chemotherapy in leukemia) - disorders causing ↑ATP degradation (e.g. alcohol abuse)
(b/c a large # of cells are lost from chemotherapy & therefore will increase uric acid levels) - Decreased uric acid secretion - renal problems
- competitive anions (e.g. ketoacidosis)
(in diabetics - b/c urine will be acidic & therefore decrease uric acid secretion) - Increased reabsorption
- drugs (e.g. diuretics)
- dehydration (increase precipitation of acid & therefore increase reabsorption of acid)
- idiopathic causes
What are conditions that potentiate urate crystal formation?
- DECREASED SOLUBILITY
- low temperature
- low pH
- TRAUMA / disturbance to joint or soft tissue
- DEHYDRATION of the joint resulting in super- saturation in the joint
- makes fluid in joints decrease & acid increase & therefore precipitate
What is the pathogenesis of gout?
- Precipitation and accumulation of urate crystals in the joint leads to joint damage and deformation.
- acute & is v. painful
- INFLAMMATION in gout is TRIGGERED by precipitation of monosodium urate (MSU) crystals into the joints, which result in production of CYTOKINES that recruit LEUKOCYTES.
- MACROPHAGES phagocytose MSU and the intracellular sensor, inflammasome, recognizes the crystals.
- Inflammasome activates CASPASE-1, which is involved in the production of biologically active CYTOKINES, most notably IL-1.
- IL-1 is proinflammatory and promotes accumulation of NEUTROPHILS and MACROPHAGES in the joint.
- These cells, in turn, release other cytokines, free radicals, proteases and arachidonic acid metabolites, all of which RECRUIT MORE LEUKOCYTES and DAMAGE THE JOINT.
- Urate crystals may also ACTIVATE the COMPLEMENT system, leading to generation of chemotactic complement byproducts. (chemokins)
** These cascades trigger an ACUTE ARTHRITIS, which typically remits SPONTANEOUSLY in days to weeks.
- REPEATED attacks of acute arthritis lead eventually to chronic tophaceous arthritis and FORMATION OF TOPHI in inflamed synovial membranes and periarticular tissue.
- from precipitation
- Severe damage to the cartilage develops and FUNCTION of JOINTS is compromised.
(*good image on slide 39)
The distinctive morphologic changes in gout include:
- Acute arthritis
- Chronic tophaceous arthritis
- Tophi in various sites
- Gouty nephropathy
Describe Acute arthritis (morph. change)
- neutrophilic infiltrate (increase) in synovium and synovial fluid
- MSU crystals in cytoplasm of neutrophils
- synovium is edematous and contains lymphocytes, plasma cells, macrophages, and small clusters of MSU
- when episode of crystallization abates and crystals are resolubilized, acute attack remits
Describe Chronic tophaceous arthritis (morph. change)
(continued pain)
- evolves from repetitive precipitation of urate crystals
during acute attacks - MSU encrusts articular surface and forms deposits in synovium
-synovium becomes hyperplastic, fibrotic, and thickened by inflammatory cells
*- pannus formation, destruction of underlying cartilage and juxta-articular bone erosions
(diff structure of pannus than RA mainly composed of uric acid)
*- severe cases: fibrous and bony ankylosis, loss of joint function
(if detect crystals it confirms its gout & rules out OA/RA)
Describe Tophi in various sites (morph. change)
-Tophi are hallmark of gout, formed by large aggregations of urate crystals surrounded by inflammatory reaction of foreign body giant cells (that are trying to get rid of crystals)
- Tophi may appear in articular cartilage, ligaments, tendons, and bursae
- Less common in soft tissues (earlobes, fingertips), kidney
Describe Gouty nephropathy (morph. change)
- renal complications caused by MSU crystals or tophi (crystals will precipitate in kidney - kidney stones)
- uric acid nephrolithiasis and pyelonephritis (urates may induce urinary obstruction)
(obstruction in kidney that leads to build-up of fluid in kidney & potential risk of infection –> can lead to kidney failure)
- hard to detect without polarized light & other
Describe 3 key parts of the pathology of gout
A. Amputated great toe with white tophi involving the joint and soft tissues
- pain is unbearable in patients
B. Gouty tophus—an aggregate of dissolved urate crystals is surrounded by reactive fibroblasts, mononuclear inflammatory cells, and giant cells
C. Urate crystals are needle shaped and negatively birefringent under polarized light (detected by polarized light)
Different stages of gout:
ASYMPTOMATIC HYPERURICEMIA –> ACUTE INFLAMMATORY GOUT
(symptoms: erythema (redness), joint inflammation, PAIN) –> INTERCRITICAL PHASES
(symptoms: none; clinically silent deposition of urate crystals –> ADVANCED GOUT
(symptoms: frequent or constant joint pain, tophi, complications associated with gout)
- b/c no symptoms
Describe the Acute Gout Clinical Manifestations
** RAPID ONSET (diff. b/t gout & RA/OA)
* frequently begins AT NIGHT
* severe join inflammation
- erythema, warmth, swelling
* fever, chill, malaise
* subside spontaneously within 3-10 days
* 90% of initial attacks are monoarticular
Describe the Chronic Gout Clinical Manifestations
- after several acute mono- or oligoarticular attacks, some patients develop chronic NONSYMMETRIC synovitis
What are the risk factors for gout?
** Hyperuricemia (plasma urate >6.8 mg/dl) is NECESSARY, but NOT SUFFICIENT, for development of gout.
- Major risk factors:
- age and sex
- duration of hyperuricemia (gout: after 20-30 yrs)
- family history of gout
- heavy alcohol consumption
- obesity
- drugs that reduce urate excretion (thiazides, salicylates) (b/c change of pH of urine)
- diet (high levels of animal proteins)
- diabetes, hypertension, atherosclerosis
What are diagnostic tests for gout (lab & radiography)?
Laboratory tests (are SPECIFIC/HELPFUL)
* serum uric acid (confirm diagnosis)
* 24 h urine uric acid (to assess risk of kidney stones)
- b/c sometimes depends on diet throughout day ?
* synovial fluid test (even if clinical appearance strongly suggests gout, diagnosis SHOULD BE CONFIRMED by needle aspiration of
inflamed joints (UA crystals)
Radiography
* X-Ray findings are not specific
* does not help to differentiate
between RA, OA, and gout
* (can show) cystic changes
What is the treatment goals for gout?
Treatment goal is to control INFLAMMATION and PAIN
Two approaches are used:
1. control of inflammation:
- NSAIDS
- Glucocorticoids
*Diff. additional one
2. decrease deposition of urate in joints:
- hyperuricemic therapy (↓ production, ↑ excretion, ↑breakdown of uric acid)
Differences b/t RA & OA
Age of onset:
RA: 3rd to 5th decade of life
OA: >45 years of age
Differences b/t RA & OA
Signs and symptoms:
RA: morning stiffness, pain, joint swelling, systemic
features, pain worsened at night
OA: Deep ache in involved joints, pain worsened by use, crepitus, non-symmetrical pattern
Differences b/t RA & OA
Joint distribution:
RA: Fingers (middle joints), wrists, knee, hands, ankles
OA: First and middle finger joints, hips, knees, cervical and lumbar spine
Differences b/t RA & OA
Radiographic findings:
RA: Juxta-articular osteopenia, erosions, narrowing of
joint space
OA: Osteophytes, sclerosis, narrowing of joint space
Differences b/t RA & OA
Laboratory findings:
RA: elevated ESR, RF(+)
OA: normal ESR, RF (-)
Gout is a…
chronic disease caused by overproduction or underexcretion of uric acid.
Gout presents…
mono- or oligoarticular joint inflammation.
Gout starts with…
acute attacks which are very painful followed by chronic attacks in some patients.
Gout diagnosis is confirmed by…
the presence of uric acid crystals in the joint in the presence of clinical findings.
