Joints and Connective Tissue Pathology

Question 1

Basic Structure and function: solid vs cavitated

Answer 1

Solid (non-synovial) – AKA synarthroses
Structural integrity, minimal movement
No joint space
Defined by joint attachement
Fibrous- cranial sutures & jaw and tooth root
Cartilaginous- symphyses (manubriosternalis and pubic)

Cavitated (synovial)

Question 2

Basic Structure and function

Answer 2

Synovial joints – joint space
Wide range of motion
Occur between bones formed by endochondral ossification
Joint space lined by synovial membrane

Question 3

Types of synoviocytes?

Answer 3

Type A synoviocytes – specialized macrophages

Type B synoviocytes – synthesize hyaluronic acid
No basement membrane
Allows for nutrient, gas and waste exchange between synovial fluid and blood

Question 4

Hyaline cartilage

Answer 4

Hyaline cartilage – shock absorber & wear-resistant surface
No blood supply, lymphatic drainage, or innervation
Composed of
Type II collagen – resist tensile stress; transmit vertical loads
Water* & proteoglycans – resistance & limiting of friction
Chondrocytes – synthesize & digest matrix
Secrete inactive forms of degradative enzymes & enzyme inhibitors

Question 5

Osteoarthritis

Answer 5

AKA degenerative joint disease
Degeneration of cartilage  structural & functional failure of joints
Most common joint disease
Phenomenon of aging
5% younger patients secondary to a predisposing condition
Joint deformities or underlying conditions
F: knees & hands
M: hips

Question 6

Osteoarthritis: symptoms and treatment

Answer 6

Deep achy pain that worsens with use, morning stiffness, crepitus, limited range of movement
Involved joints: hips, knees, lower lumbar & cervical vertebrae, proximal & distal interphalangeal joints, 1st carpometacarpal joints, & 1st tarsometatarsal joints
Disease severity on imaging DOES NOT correlate well with pain & disability
Tx: pain management, activity modification, arthroplasty

Question 7

Phases of Osteoarthritis

Answer 7

Degeneration of articular cartilage & disordered repair
Phase 1: chondrocyte injury – related to genetic & biochemical factors
Phase 2: early osteoarthritis
Chondrocytes proliferate & secrete factors to remodel cartilaginous matrix
Phase 3: late osteoarthritis
Repetitive injury & chronic inflammation
Marked loss of cartilage & bone changes

Question 8

?

Answer 8

Early – chondrocytes proliferate
Horizontally arranged collagen fibers are cleaved
Fissures at articular surface
Manifests as soft articular surface
Chondrocytes die  full thickness sloughing of cartilage
Loose bodies
Exposed bone becomes new articular surface

Question 9

Rheumatoid Arthritis (RA)

Answer 9

Chronic inflammatory disorder of autoimmune origin
Affects joints by producing a nonsuppurative proliferative and inflammatory synovitis.
 destruction of articular cartilage and ankylosis of joints
Extra-articular manifestations
Skin, heart, blood vessels, lungs
2nd – 4th decades F>M
CD4+ T cells produce cytokines (TNF)  tissue injury

Question 10

RA symptoms and treatment

Answer 10

Malaise, fatigue, musculoskeletal pain

Symmetric; 1st small joints, then larger joints

Warm, painful, morning stiffness

Progressive joint enlargement & decreased range of motion  ankylosis

Imaging: effusions & juxta-articular osteopenia with erosions, narrowing of joint space, loss of articular cartilage

Tx: steroids, methotrexate, TNF antagonists

Question 11

?

Answer 11

Rheumatoid Arthritis

•Symmetric arthritis•Small joints of hands & feet•Pannus•Synovial cell hyperplasia•Dense inflammatory infiltrates•Angiogenesis•Fibrinopurulent exudate•Osteoclast activity in bone•Pannus will bridge opposing bone à ankylosis

Question 12

?

Answer 12

•Rheumatoid nodules in skin•Firm, non-tender, round to oval•Resemble necrotizing granulomata•Central zone of fibrinoid necrosis•Prominent rim of macrophages, lymphocytes, & plasma cells

Question 13

?

Answer 13

•Severe erosive disease with rheumatoid nodules•Acute necrotizing vasculitis•Small & large arteries•In pleura, pericardium, or lung à fibrosis•Obliterating endarteritis causes peripheral neuropathy, ulcers, & gangrene

Question 14

Ankylosing spondylitis

Answer 14

•Destruction of articular cartilage•Bony ankylosis•Sacroiliac & apophyseal joints•2^nd – 3^rd decades of life•HLA-B27

Question 15

Psoriatic Arthritis

Answer 15

Question 16

Septic Arthritis

Answer 16

Question 17

?

Answer 17

•Acutely painful, swollen joint•Restricted range of motion•Fever, leukocytosis•Knee most common•Purulent fluid•Culture can identify causative agent

Question 18

Lyme Arthritis

Answer 18

Question 19

Gout

Answer 19

•Age & duration of hyperuricemia•Men > 30 years old•Genetic predisposition (family hx, HGRPRT deficiency, etc.)•Heavy alcohol consumption•Obesity•Lead toxicity•Drugs that reduce excretion of urate (i.e. thiazides)•Renal failure

Question 20

Stages of gout

Answer 20

•4 clinical stages•Asymptomatic hyperuricemia•Acute arthritis – monoarticular; 1^stmetatarsophalangeal joint (50%)•Asymptomatic intercritical period - resolution with symptom free interval•Chronic tophaceous gout – x-rays show juxta-articular bone erosion

Question 21

Answer 21

•Acute arthritis•Dense neutrophilic infiltrate•Monosodium urate crystals•Slender & needle shaped•Negative birefringent•Edematous synovium•Scattered inflammation

Question 22

? stage

Answer 22

•Chronic tophaceous arthritis – repetitive precipitation of urate crystals•Visible deposits in synovium•Thickened synovium forms a pannus•Destroys underlying cartilage•à bone erosions

Question 23

?

Answer 23

•Tophi – pathognomonic of gout•Aggregates of urate crystals•Surrounding inflammatory reaction•Cartilage, ligaments, tendons, soft tissues, kidneys•Ulcerate through skin

Question 24

Calcium pyrophosphate crystal deposition disease (CPPD)

Answer 24

•AKA pseudogout•> 50 years old•Unknown why/how crystals form•Articular cartilage proteoglycans degraded à allows crystallization around chondrocytes•Crystal deposition into the joint à inflammation & joint damage

•Frequently asymptomatic•Can cause acute, subacute, or chronic arthritis•Mono- or polyarticular arthritis•Knees*, wrists, elbows, shoulders, & ankles•50% significant joint damage•Rx: supportive therapy

Question 25

Answer 25

CPPD •1^st deposit in cartilage, menisci, intervertebral discs•Enlarged deposits can rupture à seed joint•Chalky white friable deposits•Blue-purple aggregates on histology•**Rhomboid, positively birefringent**

Question 26

Answer 26

Ganglion Cyst •1-1.5 cm cyst•Near joint capsule or tendon sheath•**Wrist** common•Cause: cystic/myxoid degeneration of connective tissue•**No true cyst lining**

Question 27

Answer 27

Synovial cyst •Cause:•Herniation through a joint capsule•Massive enlargement of a bursa•Popliteal space in RA = Baker cyst•Hyperplastic synovial lining•Inflammatory cells & fibrin

Question 28

Tenosynovial Giant Cell Tumor

Answer 28

•Closely related benign neoplasms developing in the synovial lining of joints, tendon sheaths, and bursae•Variants•Diffuse type – large joints•Localized type – discrete nodule attached to a tendon sheath•**t(1;2)** – fusion of type IV collagen promoter to of M-CSF gene•à overexpression of M-CSF à stimulates proliferation of macrophages ## Footnote •**Diffuse – knee\*, h**ip, ankle, calcaneocuboid joints•Pain, locking, recurrent swelling•Limited range of motion•If aggressive can erode into bone & soft tissue•**Localized – tendon sheaths of wrists & fingers**•Solitary, slow growing, painless•Bone erosion in 15%•Tx: surgical excision (often recur)

Question 29

Answer 29

Tenosynovial giant cell tumor •Red-brown to yellow-orange•Few neoplastic cells•Resemble synoviocytes•Diffuse – tangled mass with finger-like projections•Tumor cells are infiltrative

Question 30

?

Answer 30

Tenosynovial giant cell tumor •Localized – well circumscribed•Solid aggregate•Attached by a pedicle•Heavy macrophage infiltrate

Question 31

Giant Cell Tumor of Bone

Answer 31

•Epiphysis•Extend to metaphysis•**Knee**•Arthritis-like symptoms•Solitary•Rx: Currettage (recur)

Question 32

Answer 32

Giant cell tumor of bone •Bulging soft tissue mass•Thin shell of reactive bone•Cystic degeneration•**Sheets of mononuclear cells**•**Numerous benign osteoclast-type giant cells**

Question 33

Answer 33

Aneurysmal bone cyst (ABC) * **Tumor characterized by multiloculated blood-filled cystic spaces**•First 2 decades of life•**Metaphysis of long bones & posterior vertebrae**•Pain & swelling•Chromosome 17 rearrangements•**USP6 overexpression à increased NF-κB activity à bone resorption**•Tx: surgical curettage * Eccentric•**Expansile**•Well-defined margins•Lytic•**Thin shell of reactive bone**

Question 34

Answer 34

Aneurysmal bone cyst (ABC) •**Blood-filled cystic spaces**•Uniform fibroblasts•**Osteoclast-like giant cells**•Reactive woven bone