Joint Anatomy and Histology; Pathology of Osteoarthritis and Rheumatoid Arthritis

Question 1

What is the most common type of movable joint and what do the cells secrete to maintain it?

Answer 1

Diarthrodial / synovial joint

Synovial cells secrete hyaluronic acid to make the ultrafiltrate of plasma that is secreted into the joint even thicker.

Question 2

What type of joint does the intervertebral disc make?

Answer 2

Amphiarthrodial -> limited mobility

Question 3

What are the two components of the intervertebral disc? What do they attach to?

Answer 3

1. Annulus fibrosus - fibrocartilage, made from sclerotome. Attach to vertebral bodies via Sharpey fibers.
2. Nucleus pulposus - Gelatinous core of proteoglycans and water, which resists compression. Separated from vertebral bodies via hyaline cartilage (articular).

Question 4

What are the two types of synarthroses and an example of each?

Answer 4

1. Fibrous - i.e. skull sutures

2. Cartilaginous - i.e. pubic symphysis

Question 5

How does hyaline articular cartilage receive its nutrients and what is it good for resisting mechanically?

Answer 5

Receives its nutrients from diffuse of nutrients from synovial fluid

Good for resisting compression

Question 6

What is hyaline cartilage made out of that makes it good at resisting compression?

Answer 6

Proteoglycans
-> i.e. aggrecan molecules bound to hyaluronic acid, with carbohydrate side chains of keratan and chondroitin sulfate
Highly charged and attract water

Also has type II collagen running superficially parallel and deeply perpendicular to the joint interface

Question 7

What is the bone-hyaline cartilage interface like? Why is it like this?

Answer 7

Noncalcified cartilage -> tidemark (where calcified cartilage meets noncalcified cartilage) -> calcified cartilage -> subchondral bone

This prevents weakness at the bone-cartilage interface

Question 8

What is fibrocartilage made of and what is it good for? Where is it found?

Answer 8

Made of type 1 collagen as well as hyaline cartilage (a mix of the two). Good for resisting tension

Found in the menisici of the knee, annulus fibrosus, and insertions of ligaments / tendons on bone

Question 9

What structures does the synovial membrane line?

Answer 9

Inner surface of the joint capsule and other intra-articular structures EXCEPT articular cartilage and menisci

Bursae

Tendon sheaths

Question 10

What is the structure of the synovial membrane (two layers)?

Answer 10

1. Synovial lining cells -> a few layers thick, producing hyaluronic acid, phargocytosing debris, and mediating nutrient and waste exchange between blood and synovial fluid
2. Subsynovial loose connective tissue -> with immune cells, capillaries, lymphatics, and nerves. Regulates the synovial fluid movement.

Question 11

How does cartilage change as you age?

Answer 11

Cartilage loses water content due to change in composition of proteoglycan molecules

Question 12

What is primary vs secondary osteoarthritis and who gets secondary?

Answer 12

Primary = idiopathic, associated with wear and tear

Secondary - Happens in younger individuals with previous joint injury or deformity, or a systemic disease affecting the joints

Question 13

What is the pattern of joint involvement in primary osteoarthritis? Men vs women?

Answer 13

Oligoarticular, affecting especially the weight-bearing joints.

Knees and hands - affected in women. Hands are very familial.

Hips - affected in men

Cervical and lower lumbar vertebrae - affected in both

First tarso-metatarsal joint -> from stepping off of foot

Question 14

What pathology is seen in the articular cartilage in early vs late osteoarthritis?

Answer 14

Early - proliferation of chondrocytes with secretion of inflammatory mediators -> alteration in composition of cartilaginous matrix. Inflammation begins in synovium (mild, chronic “-itis”) and underlying subchondral bone.

Late - Marked loss of cartilage and abnormalities of subchondral bone. Cartilage shows fissures and clefts, called “fibrillation”

Question 15

What pathologic features characterize the joint in general in osteoarthritis?

Answer 15

1. Joint space narrowing -> cartilage thinning leads to less radiolucent space between bones
2. Joint mice (loose bodies) - sloughed cartilage +/- bone into joint

Question 16

What happens to the exposed subchondral bone in osteoarthritis?

Answer 16

1. Friction with opposing surface -> bone becomes eburnated and sclerotic
   Eburnated means smooth and polished.
2. Formation of subchondral cysts -> small fractures in bone allow synovial fluid to enter bone.

Question 17

What are osteophytes? Do they have cartilage on them?

Answer 17

Bone spurs -> reactive bony outgrowths at the margins of the articular surface

They are capped by cartilage. They grow laterally because they can’t make bone on the weightbearing surface (they would get crushed).

Question 18

What are the clinical symptoms of osteoarthritis, and what problems can osteophytes of the vertebrae cause?

Answer 18

Insidious onset of joint pain worse with activity, morning stiffness (<30 min), and decreased range of motion

Vertebral osteophytes -> can impinge on spinal nerve roots and cause neural problems

Question 19

What are osteophytes of the hands in osteoarthritis called?

Answer 19

PIP - Bouchard nodes (think BP)

DIP - Heberden’s nodes

Question 20

What genetic markers are associated with development of rhuematoid arthritis?

Answer 20

1. HLA-DRB1 - common epitope for presentation in MHC Class II
2. HLA-DR4 - 4 walls in a rheum
3. PTPN22 - protein tyrosine phosphatase - plays a role in inhibition of T cell activation. Increased risk if lost.

Question 21

What is the process by which autoimmunity is thought to arise in RA?

Answer 21

Tissue injury i.e. via bacterial infection in combination with smoking to increase the inflammation -> lysis of cells and exposure of citrullinated self-peptides via MHC -> creation of autoantibodies to citrullinated self antigens

Bacteria also have some epitopes which look like citrullinated peptides as well which may contribute via molecular mimicry

Question 22

How does cell-mediated immunity play a role in pathogenesis of RA?

Answer 22

1. Th1 cells -> secrete IFN-y to activate macrophages and synoviocytes
2. Th17 inflammatory cells -> chemotaxis of neutrophils and monocytes
3. Macrophages secrete TNFa and IL-1 -> stimulate metalloprotease release by synoviocytes to destroy atrticular cartilage
4. Activatd T cells express RANKL -> activate osteoclasts and bone resorption

Question 23

What are the sensitive and specific antibodies for RA?

Answer 23

Sensitive: anti-CCP (cyclic citrullinated peptides) + rheumatoid factor (IgM or IgA antibodies against the Fc portion of IgG - unclear if involved)

Specific: anti-CCP most specific

Question 24

What forms cyclic citrullinated peptides?

Answer 24

Arginine residues are post-translationally converted to citrulline.

Question 25

What type of inflammatory infiltrate characterizes the synovium and the joint fluid proper in RA?

Answer 25

Synovium: chronic inflammatory infiltrate with T cells and B cells responding and presenting CCP antigens

Synovial fluid: Neutrophilic infiltrate -> immune complex deposition in joint (ultrafiltrate of plasma) activates complement. C5a attracts neutrophils and promotes cell lysis, which allows further exposure of citrullinated peptides.

Question 26

Who does rheumatoid arthritis tend to affect? Is it symmetric? How does it change with activity?

Answer 26

Young women. Insidious onset, with relapsing and remission.

Symmetric involvement of joints, especially small joints of hands and feet. Very warm and tender with effusions (due to inflammation, vs. OA)

Very stiff for >1 hour following inactivity

Question 27

What is the pannus which is formed in RA? How does it invade?

Answer 27

The edematous, thickened synovial tissue with a villous transformation
-> it is thickened by chronic inflammation and secretes many inflammatory factors, invading from the periphery of the joint capsule onto the articular surface (vs OA which is solely articular surface involvement)

Question 28

How do the bone changes in RA distinctively differ from OA?

Answer 28

RA -> T cell expression of RANKL leads to bone thinning and destruction

OA -> subchondral sclerosis is characteristic, the exact opposite

Question 29

How does the pannus appear microscopically? Where does articular cartilage erosion begin?

Answer 29

Synovial cell hyperplasia, chronic inflammation, and granulation tissue

Osteoclasts will be seen adjacent to bone, and will lead to resorption of subchondral bone.

Articular cartilage erosion begins periarticular (at the edges) since that’s where the joint inflammation is.

Question 30

What happens to the tissues adjacent to the diseased joints in RA? Describe the hand deformities.

Answer 30

Extension of inflammation into neighboring soft tissues (Tendons / ligaments) -> loss of joint stability

1. Radial deviation of wrist
2. Ulnar deviation of fingers
3. Swan-neck deformity - hyperextension of PIP and flexion of DIP
4. Boutonniere deformity - flexion of PIP and hyperextension of DIP.

Question 31

What can the pannus due to two adjacent bones that makes them highly immobile and decreases their range of motion?

Answer 31

Fibrous and bony ankylosis - Fusion of joint and fibrous tissue -> pannus is granulation tissue and can fuse bones together like a scar.

Can happen in any inflammatory arthritis.

Question 32

Give an example of a synovial herniation in RA and why it happens?

Answer 32

Inflammation and edema into the synovial joint causes a synovial herniation.

Commonly happens behind the knee -> popliteal fossa. This is called a “Baker cyst”

Question 33

Where are rheumatoid nodules and what is their histology?

Answer 33

They are usually found in areas of tissue damage -> i.e. on hands and elbows where damage would occur and allow citrullinated peptides to be exposed.

Histology: Fibrinoid necrosis with palisading histiocytes

Question 34

What systemic disease can RA cause with regards to blood vessels / nerves?

Answer 34

Can cause a leukocytoclastic vasculitis with purpura and ulcers

Can also cause a carpal tunnel syndrome and uveitis (need to check with ophthalmologist)

Question 35

What can RA cause in the lungs?

Answer 35

It is known to cause intertitial lung fibrosis. Can be caused when rheumatoid nodules appear in lungs. Some people think this often happens before joint involvement.

Nodules can also be found in lung in combination with pneumoconiosis -> Caplan syndrome

Endstage: honeycomb lung

Question 36

What systemic late complications can occur due to RA?

Answer 36

1. AA amyloidosis -> due to prolonged chronic inflammation

2. Opportunistic infections -> secondary to chronic immunosuppression