MSS15 Pathology Of Inflammatory And Degenerative Joint Disorders Flashcards
1
Q
Synovium
A
Synovium = Synovial membrane
Vascular tissue with inner layer of synovial cells
2 types of synovial cells:
Type A: macrophage like cells
Type B: make proteins esp. ***hyaluronic acid of synovial fluid
2
Q
Synovial fluid
A
***Ultrafiltrate of blood plasma
Addition:
- ***hyaluronic acid
- proteinase
- collagenase
- prostaglandins
Without:
- RBC
- clotting factors
- haemoglobin
3
Q
Cartilage
A
- ***No basement membrane –> allow H2O passes freely in and out of cartilage
- Avascular (obtain nutrient by diffusion from bone, only 2 ways nutrients enter)
- Aneural
- Alymphatic
- No capacity to repair structural damage due to injury / disease
Content: 1. Chondrocytes (1%) 2. ***Water (70%) 3. ECM (structural macromolecules) - ***Type II collagen (60%) - ***Proteoglycan —> Protein core + ***Glycosaminoglycan e.g. ***hyaluronic acid, chondroitin sulfate, keratan sulfate, dermatan sulfate) chains - ***Glycoproteins and Non-collagenous proteins
4
Q
ECM Constituents produced by chondrocytes
A
- ***Type 2 collagen
- hold cartilage together - Proteoglycan
- Aggrecan (up to 200 large PG molecules): ***trap water - Hyaluronic acid
- backbone that Aggrecan binds to
- gives cartilage ***compressive stiffness
5
Q
Only 2 ways nutrients enter cartilage
A
- Subchondral (beneath cartilage i.e. from bone)
- Diffusion from synovial fluid
- -> weight load pushes H2O out
- -> weight load removed then H2O + nutrients move back in
6
Q
Matrix continually turning over by
A
- Matrix Metalloproteinases (MMP)
- physiological resorption of macromolecules and collagen (cell produce proteoglycans and MMP breaks them down)
- e.g. Collagenase, Gelatinase - Inhibitors of metalloproteinases (TIMP)
7
Q
2 functions of cartilage
A
- ***Distribute load over bone surfaces
2. Provide ***low-friction surface over which bone can move
8
Q
***Zones of articular cartilage
A
- Lamina splendens
- outermost
- resists tension
- collagen ***Parallel to surface
- glucose can diffuse in
- hyaluronic acid cannot escape - Tangential zone
- flatter
- ***elongated chondrocytes - Transitional and Radial zone
- **typical looking chondrocytes
- chondrocytes may stack
- collagen **radiates Inward to act as anchor - Tidemark
- boundary between transitional and calcified zone - Calcified cartilage
- chondrocytes in dark staining matrix due to **increased mineral content
- junction between it and subchondral bone is **irregular to hold cartilage in place - Subchondral bone
9
Q
Joint
A
Cartilage capsule lined by Synovium / Synovial membrane
10
Q
5 common disorders of joint
A
- Osteoarthritis
- Rheumatoid arthritis
- Ankylosing spondylitis
- Gout
- Calcium pyrophosphate dihydrate (CPPD)
11
Q
- Osteoarthritis
A
- Normal balance between cartilage synthesis and degradation is disrupted, often with inflammation
- Loose bodies (bits of cartilage broken off) often accompany, survive within joint and grow
- Spine commonly affected: sclerosis of endplate of vertebral body with osteophyte formation may compress nerve
- High economic cost
2 types:
- Primary / Idiopathic
- mostly older people
- affect single weight bearing joint
- usually Overweight (US) / Poor posture (HK) - Secondary
- trauma / occupation
Pathogenesis:
- Abnormal load
- -> normal cycle of nutrient supply lost
- **Underloading –> poor diffusion from synovial fluid –> poor chondrocyte nutrition
- **Overloading –> no fluid moves in –> chondrocyte death - Disturbed regulation of matrix formation by MMP / stromeolysin
- **cleaves collagen 2
- -> loses framework
- -> fibrillation, erosion, cracking
- -> **more H2O moves in and bind to aggrecan (trap water) (水由外面經Collagen裂縫進入Cartilage)
- -> ***swelling of matrix and cleaving of aggrecan
- -> loses compressive and tensile stiffness
- -> more abnormal loading of joint - Repair process failed to reproduce normal balance of mature tissue compounds
- chondrocytes respond to damage in only 1 way
- -> proliferation to ↑ enzymes + growth factors
- -> imbalance between synthesis and degradation of matrix (degradation > synthesis)
- -> ***Abnormal distribution and composition of components of matrix - Remodelling of joint to adapt to abnormal weight distribution:
- -> **Subchondral sclerosis (fibrosis of fibrous tissue support framework beneath cartilage –> interfere with nutrition)
- -> **Osteophyte formation (bony outgrowths at joint margin, stabilize the joint but source of pain and not physiological; DIP of hands: Heberden’s nodes) - ***Subchondral cyst
- loss of cartilage leads to high pressure from joint forming a cyst in bone where pressure is lower
Radiological appearance:
- Loss of joint surface (erosion of cartilage)
- Bone cyst formation
- Osteophyte formation
- Subchondral sclerosis
Histological appearance:
- Fibrillation
- Clefting
- Cellular proliferation
- Eburnation (loss of cartilage)
- Non-specific synovitis
12
Q
- Rheumatoid arthritis
A
- Common, Progressive, Chronic, ***Systemic disease of unknown etiology
- Progressive **symmetrical **synovitis with pain + stiffness
—> deformity and destruction of joints of young to middle-aged Females - genetic factors: 50%
- systemic but attack joints
ACR-EULAR definition:
- confirmed presence of synovitis in >= 1 joint
- absence of alternative diagnosis for the observed arthritis
- total score >= 6 from 4 domains:
1. No. and site of involved joint
2. **Serological abnormalities
3. **Elevated acute-phase response
4. Symptom duration
Causes:
- Genetics
- Environment (smoking, bacteria, dust / silica)
—> trigger inflammation in mucosal sites e.g. gums, lungs, gut - Autoimmune
1. Activation of immune system
—> minor trauma **↑ expression of citrullinated proteins in normal healthy joints (joint: second hit)
—> osteoclasts express enzyme that also **↑ citrullination of collagen 2 in cartilage leading to attack by AutoAb
—> ***APCs + dendritic cells presenting citrullinated proteins (post-translational modification of proteins) to immune system
- AutoAb formation (can be detected before disease onset)
- CD4 Th cells
—> initiate response by reacting with an agent to produce cytokines
—> stimulate ***macrophages (through IFNγ), Th17 (through IL17) - Macrophage infiltration
—> with release of TNFα + IL1 (intensity of infiltration correlates with disease activity and radiological progression)
—> 1. stimulate synovial cells to produce **enzymes that destroy cartilage
—> 2. +ve feedback between TNFα and factors by fibroblasts: chemotactic for **monocytes
—> 3. AutoAb to citrullinated peptide (CCP) - Rheumatoid factor
—> serum IgM / IgA AutoAb that bind to Fc IgG (antibody against Fc portion of IgG)
—> Immune complex formation
End result:
**Acute **destructive **inflammatory **synovitis
—> AutoAb against citrullinated vimentin (structural filament in fibroblasts): **cross reactive with other citrullinated antigen
—> lead to osteoclast-dependent **bone destruction
Clinical manifestation:
1. Malaise, viral-type feeling
(triggering of immune system)
- Fatigue, weight loss
(enhancement of immune response) - Joint pain, swelling, tender, stiff, limitation in ROM
(activation of immunologically active cells + elaboration of inflammatory cytokines) - Joint damage, erosions, joint space narrowing
(activation of synovial and cartilage by tissue damaging enzymes) - ***Pannus formation
(vascularized granulation tissue)
X-ray appearance predictable:
- Osteopenia (low bone density) of juxtaarticular bone (inflammation of subchondral bone)
- Hyperaemia (inflammation of synovium)
- Erosions
- Joint space narrowing
13
Q
- Ankylosing spondylitis / Rheumatoid spondylitis / Marie-Strumpell disease
A
- ***repeated inflammation of ligament lead to ossification and rigidity
- young adult males
- pain and morning stiffness of back
- ***eventual ankylosis
- peripheral joints involved later
- 90% ***HLA B27 +ve
- Histologically: ***Endochondral ossification (bone formation) in articular cartilage / IV disc
14
Q
- Gout
A
- Deposition of chalky deposits of ***Sodium Urate crystals in affected joints
- Risk factors:
1. genetics
2. excessive intake of ***purine
Primary: ***Hyperuricaemia (less common)
Secondary:
- ↑ uric acid production by cell breakdown (Haemic malignancies —> ***Tumour lysis syndrome)
- ↓ uric acid excretion (***Chronic renal disease)
- ***Inflammasome (NLRP3) plays a big role (cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses)
Acute stage:
- Acute painful arthritis (as needles destroy neutrophils)
- affect ***1st MTP joint (雞眼位)
- Cardinal features of acute inflammation
- joint is not normally arthritic
Intermediate stage:
- diffuse deposits seen due to deposition of monosodium urate crystals in body, particularly ***Kidneys + Periarticular region
- deposits –> bone erosion
Histological appearance:
- **Needle-shaped crystal surrounded by fibrous tissue and rimmed by **Mononuclear histiocytes (mononuclear phagocyte) and ***Giant cells
15
Q
- Calcium pyrophosphate dihydrate (CPPD)
A
2 presentations:
- Acute synovitis (mimic gout)
- ***Pseudogout
- Superimposed on chronic arthropathy
- elderly women - Chronic pyrophosphate arthropathy (mimic OA)
- unlike OA commonly affect Radiocarpal, Glenohumeral, Midtarsal joints (**Atypical joints)
- Deposition of **rhomboidal CPP crystals (different crystal shape than urate crystal) from cartilage into joint space
(Normally:
- ATP from cells –> pyrophosphate + AMP; pyrophosphate –> inorganic phosphate by alkaline phosphatase
- under influence of growth promoting factors pyrophosphate complexes with Ca to form crystals)
X-ray:
Calcification of knee cartilage (Chondrocalcinosis) + Menisci
CPPD often ***associated with OA
- OA contains replicating / damaged cells which ***release ATP
- changes in cartilage matrix also interfere with growth factors (trigger Ca + pyrophosphate —> CPP crystal)
