2. Learning Objectives
State inflammatory mediators of joints
Know pathogenesis of arthritis
Describe changes in joints due to inflammation and ageing.
Explain patho-physiology and main clinical investigations for osteoarthritis,
gout and rheumatoid arthritis.
3. Arthritis
Inflammation of the joints, common types of arthritis includes;
Osteoarthritis (degenerative)
Rheumatoid arthritis (autoimmune)
Ankylosing spondylitis (genetic disease)
Suppurative arthritis (infectious)
Gouty arthritis
4.
5. Osteoarthritis(OA)
Characterized by degeneration of articular cartilage of synovial Joints
Primary osteoarthritis:
An aging phenomenon / genetic predisposition
Secondary osteoarthritis:
Predisposing condition like; joint deformity or after joint injury
6. OA: Pathogenesis
Early
Fissures/clefts at articular surface, chondrocytes proliferate to repair
Later
Continued degradation exceeds repair, sloughing of cartilage and
subchondral bone, form loose bodies (joint mice)
Friction between exposed subchondral bone surfaces, makes it creamy
white and hard due to sclerosis (bone eburnation)
Small fractures through articulating bone form gaps, allowing synovial fluid
into subchondral regions forming fibrous-walled cysts
Outgrowths (osteophytes) develop at the margins of articular surfaces,
capped by cartilage that gradually ossify
8. OA
Characteristic fissures and cracks of the
articular cartilage
Mushroom-shaped osteophytes (bony outgrowths )
develop at the margins of the articular surface and
are capped by fibrocartilage and hyaline cartilage
9.
10. Rheumatoid Arthritis (RA)
Chronic inflammatory disorder, autoimmune origin, principally attacks joints,
may have extra articular lesions in the; skin, heart, blood vessels, and lungs
Incidence: Male to female ratio;1:3 the peak age 3rd to 5th decades of life
Etiology:
- Autoimmune mechanism
- Genetic predisposition
- Environmental factors (Infections and smoking)
11. RA: Pathogenesis
Pathologic changes mediated by deposition of immune complexes in
the joints formed by autoantibodies against self-antigens (arthritogen)
and inflammation caused by cytokines, predominantly secreted by
CD4+ T helper cells
T cells cytokines; IFN-γ, activates macrophages and synovial cells, IL-17,
recruits neutrophils and monocytes, RANKL, stimulates osteoclasts and
bone resorption
TNF and IL-1 secreted by macrophage stimulate resident synovial cells to
secrete proteases that destroy hyaline cartilage
12. RA: Morphology
Gross: Synovium edematous, thickened and hyperplastic,
covered by delicate and bulbous villi
Microscopy: angiogenesis, neutrophils and aggregates of
organizing fibrin on synovial and joint surfaces, in chronic
cases villi shows mononuclear inflammatory cells
Pannus: a mass of edematous synovium, inflammatory cells,
granulation tissue, and fibroblasts that grows over articular
cartilage and causing its erosion. Advanced untreated
cases, pannus can bridge bones to form a fibrous
ankylosis, may later ossify; bony ankylosis (fused joint)
Rheumatoid nodule: composed of central necrosis rimmed
by palisaded histiocytes
13. Differential Diagnosis
Rheumatoid Arthritis
Young age
Female more
Morning stiffness>1 hour
Symmetrical
Small joints
Autoimmune
Synovial inflammation
Synovium- Cartilage
Rh. Factor positive
Osteoarthritis
Old age
Both sexes equal
Pain throughout the day
Asymmetrical
Large joints
Degenerative
Cartilage degeneration
Cartilage-synovium
Rh. Factor negative
14.
15. Ankylosing Spondylitis (AS)
Genetic disease, most cases associated with variation in HLA-B27
Affecting male greater than female, age incidence 3rd to 4th decade
Pathologic changes; in the ligamentous attachments rather than synovium
Arthritis with large osteophytes and destruction of articular cartilage, bone
proliferation leads to bony ankylosis (fusion of joints)
Lab diagnosis; 90% HLA-B27 positive and RF negative
Clinical manifestation; Commonly involve sacroiliac joints, spine or other
joints with lower back pain and spinal immobility
19. Suppurative Arthritis (SA)
Etiology; caused by infectious agents commonly bacteria
H. influenza; in children younger than 2 years of age
Staph. aureus; in older children and adults
Gonococcus; mainly in sexually active women
Salmonella; in sickle cell disease patients
Routes of entry; Hematogenous spread of bacteria into joints form distant
sites or by direct inoculation through skin, contiguous spread from a soft
tissue abscess or osteomyelitis
Pathology; acute suppurative arthritis with collection of pus in joint cavity
20. SA
Clinical Manifestations
Sudden onset, acutely painful, warm, swollen joint with limited joint
movements and fever
Three cardinal signs; fever, leukocytosis, and raised ESR
In 90% cases, infection involves only a single joint, most commonly knee,
followed in decreasing frequency by hip, shoulder, elbow, wrist, and
sternoclavicular joints
Joint aspiration; purulent fluid, causative agent can be identified
21.
22. Gout
Inflammatory arthritis with recurrent attacks of acute synovitis, caused by
persistent hyperuricaemia (plasma urate level above 6.8 mg/dL)
Types:
Primary (95%): inherited disorder with overproduction or under excretion of
uric acid
Secondary (5%): myeloproliferative disorders, renal disease
22
23. Gout
Pathogenesis
Uric acid; produced by catabolism of purine
Its abnormal excessive production leads to hyperuricemia
With the formation of monosodium urate crystals and its deposition into joint,
tendons and adjacent tissue, stimulates production of cytokines, recruit
leukocytes (macrophages and neutrophils which phagocytose the crystals)
Only about 10% of patients with hyperuricemia develop clinical gout
24. Gout: Morphology
Acute arthritis; dense mixed inflammatory infiltrate in the edematous
synovium and synovial fluid, neutrophils shows engulfed needle-
shaped urate crystals
Chronic tophaceous arthritis; repetitive precipitation of urate crystals
during acute attacks, visible as chalky deposits in the synovium which
becomes hyperplastic, fibrotic, and thickened by inflammatory cells and
forms a pannus that destroys the cartilage
Tophi: large aggregations of dissolved urate crystals surrounded by
reactive fibroblasts, mononuclear inflammatory cells, and foreign body
giant cells in the articular cartilage, ligaments, tendons, and bursae are
pathognomonic of gout
Gouty nephropathy; urate crystals in the renal medullary interstitium
or tubules leads to uric acid nephrolithiasis and pyelonephritis
25. Gout
Diagnosis: Presence of crystals in the joint
fluid or tophus, blood uric acid levels may be
normal during an attack
Clinical Manifestations
Patient has repeated attacks of painful, red,
hot swollen joint, sudden in onset usually
affecting the 1st MP joint (base of big toe) in
about half of cases
Gouty tophi presenting as nodules on the
finger and helix of the ear
26. Other Types of Arthritis
Reactive arthritis: defined by a triad of arthritis, nongonococcal urethritis or
cervicitis, and conjunctivitis, probably caused by an autoimmune reaction
initiated by previous infection of genitourinary system (Chlamydia) or the
gastrointestinal tract (Shigella, Salmonella, Yersinia, Campylobacter)
(More than 80% are HLA-B27 positive)
Tuberculous arthritis: chronic granulomatous synovitis
Pseudogout: inflammatory responses against precipitation of calcium
pyrophosphate crystals
27. Self-Assessment
Q. The most common type of arthritis in old age is :
A. Gouty arthritis
B. Rheumatoid arthritis
C. Osteoarthritis
D. Tuberculous arthritis
28. Self-Assessment
Q. The main pathology of osteoarthritis is:
A. Autoimmune destruction of synovial membrane
B. Degeneration of the articular cartilage
C. Osteoporosis
D. Vitamin D deficiency
29. Quiz
Q1. Name the structures which the needle has to pierce in order to aspirate
the fluid from the knee joint cavity.
Q2. Name the type of arthritis in which the inflammatory process starts from
the synovial membrane and later damage the articular cartilage.
Q3. Name the type of arthritis in which the degeneration of articular cartilage
is the earlier sign followed by involvement of the synovial membrane.
