Chapter 26: Joints Flashcards
1
Q
What are the 3 major components of hyaline cartilage?
A
70% H2O + 10% type II collagen + 8% proteoglycans
2
Q
Which joints are most commonly affected in osteoarthritis in men vs. women?
A
- Men = hips
- Women = hands and knees
3
Q
What are the 3 phases of changes to chondrocytes seen with the pathogenesis of osteoarthritis?
A
- Chondrocyte injury, related to genetic and enviornmental factors
- Early OA: proliferation for remodeling of cartilaginous matrix and secondary inflammatory changes
- Late OA: repetitive injury and chronic inflammation lead to chondrocyte drop out, marked cartilage loss, and extensive subchondral bone changes
4
Q
Which cytokines and diffusable factors have been implicated in the pathogenesis in osteoarthritis?
A
- TGF-β –> which induces MMP’s
- TNF
- Prostaglandins
- Nitric oxide
5
Q
What are 3 characteristic morphological findings of osteoarthritis?
A
- Hunks of dead cartilage sloughed into the joint –> ‘joint mice’
- Subchondrondal bone exposed and rubbed smooth = eburnation
- Microfractures and cysts develop
- Mushroom-shaped osteophytes (bony outgrowths)
6
Q
Deep, achy pain that worsens with use, morning stiffness, crepitus, and limitation of ROM is characteristic of what?
A
Osteoarthritis
7
Q
What are the prominent osteophytes which may form at the PIP and DIP joints of pt with osteoarthritis called?
A
- PIP = Bouchard’s nodes
- DIP = Heberden node
8
Q
Which joint disease may progress to deformity with time and which may progress to fusion?
A
- OA may progress to joint deformity, not fusion
- RA progresses to fusion
9
Q
OA is a disease of what vs. RA?
A
- OA = disease of cartilage
- RA = disease of synovium
10
Q
Which inflammatory cells may initiate the autoimmune response in RA and how?
A
CD4+ T helper cell by reacting with an arthritogenic agent, perhaps microbial or a self-antigen
11
Q
What are the most important cytokines isolated from the inflammed joint in person with RA; what is their role in the disease?
A
- IFN-γ from TH1 cells activate macrophages and resident synovial cells
- IL-17 from TH17 cells recruit neutrophils and monocytes
- TNF and IL-1 from macrophages stimulate resident synovial cells to secrete proteases that destro__y hyaline cartilage
- RANKL on activated T cells stimulate bone resportion
12
Q
Which cytokine has been most firmly implicated in the pathogenesis of RA?
A
TNF
13
Q
Many of the autoantibodies produced in the lymphoid organs and in the synovium of pt with RA are specific for what?
A
Citrullinated peptides (CCPs)
14
Q
What are 2 genetic factors associated with RA?
A
HLA-DRB1 alleles & PTPN22 gene
15
Q
What are 5 characteristic histologic features of RA?
A
- Synovial cell hyperplasia and proliferation
- Dense inflammatory infiltrates of CD4+ cells, B cells, plasma cells, dendritic cells, and macrophages
- ↑ vascularity due to angiogenesis
- Fibrinopurulent exudate on synovial and joint surfaces
- Osteoclastic activity in underlying bone –> periarticular erosions ad subchondral cysts
16
Q
Which characteristic mass of edematous synovium, inflammatory cells, granulation tissue, and fibroblasts growing over articular cartilage is seen in joints affected by RA?
A
Pannus
17
Q
With time in RA, the pannus bridges apposing bones to form what?
A
Fibrous ankylosis, which eventually ossifies and results in fusion of the bones, called bony ankylosis
18
Q
Which skin lesions are commonly seen in RA, what is their morphology?
A
- Rheumatoid nodules: firm, non-tender, and round arising in subcutaneous tissue
- Resemble necrotizing granulomas w/ central zone of fibrinoid necrosis + prominent rim of macrophages, lymphocytes and plasma cells.
19
Q
Where are rheumatoid nodules most commonly seen?
A
Extensor surfaces at pressure points
20
Q
How may the blood vessels of patient with RA be affected and which vessels specifically?
A
- Risk of acute necrotizing vasculitis of small and large arteries
- May involve the pleura, pericardium or lung evolving into chronic fibrosing process
- Obliterating endarteritis —> peripheral neuropathy, ulcers, and gangrene may occur
21
Q
Inflammation in the tendons, ligaments, and occassionally adjacent skeletal muscle accompanying RA produces what characteristic findings in the hands?
A
- Radial deviation of the wRrist
- UlNar deviation of the fiNgers
- Boutonniere: deformity of finger –> hyperextension of DIP w/ flexion of PIP
- Swan-neck: hyperextension of PIP, flexion of DIP
22
Q
What are the radiographic hallmarks of RA?
A
Joint effusions and juxta-articular osteopenia w/ erosions and narrowing of the joint space + loss of articular cartilage
23
Q
Diagnosis of RA, especially with presence of multisystem involvement, is supported by what 3 findings?
A
- Characteristic radiohgraphic findings
- Sterile, turbid synovial fluid w/ ↓ viscosity, poor mucin clot formation, and inclusion-bearing neutrophils
- Combo of rheumatoid factor and anti-CCP antibody
24
Q
How do the joints being affected differ between OA and RA?
A
- OA: usually large, weight bearing joints
- RA: symmetrical pattern w/ small joints affected first
25
How does activity affect the pain in OA vs. RA?
- **OA** = **_worse_** with **activity**
- **RA** = **_improves_** with **activty**, worse with rest
26
What may develop in the knee as increased intra-articular pressure causes herniation of synovium in some pt's with RA?
**Baker cyst** of the **posterior knee**
27
Which ocular changes due to blood vessel involvement may be seen with RA?
**Uveitis** and **Keratoconjunctivitis**
28
Which heterogenous group of disorders present with arthritis before age 16 and persist for at least 16 weeks?
**Juvenile idiopathic arthritis (JIA)**
29
In what 5 ways is Juvenile idiopathic arthritis (JIA) different than RA?
- **Oligo**arthritis = **more common**
- **Systemic dz** is **more frequent**
- **Large joints** affected **more often**
- **Rheumatoid nodules** and **rheumatoid factor** typically _absent_
- **Antinuclear antibody (ANA)** is **common**
30
What are the 4 features unifying the seronegative spondyloarthropathies?
- Changes in **ligamentous** attachments rather than synovium
- **Involvment** of the **SI joint** +/- others
- **_Absence_** of **RF**
- Association of **HLA-B27**
31
What joints involved in ankylosing spondylitis and typical presentation?
- Destruction of articular cartilage and bony ankylosis, typically of **sacroiliac** and **apophyseal joints**
- Involvement of **SI joint** & **vertebrae** becomes _symptomatic_ in **2nd - 3rd decade** of life as **LBP** and **spinal immobility**
32
Who is most affected by reactive arthritis and at what age?
- **Men** in their **20s** or **30s**
- Also affects pt's with **HIV**
33
Reactive arthritis most often follows what?
- **GU infection** --\> *Chlamydia*
- **GI infection** --\> *Shigella, Salmonella, Yersinia, or Campylobacter*
34
What are the common early sx's of reactive arthritis and which joints are most often affected?
- **Early sx's** = joint stiffness + LBP
- **Ankles, knees**, and **feet** are affected _most_ often; frequently **_asymmetric_**
35
What are the extra-articular manifestations that may be seen with reactive arthritis?
- Inflammatory balanitis
- **Conjunctivitis**
- Cardiac conduction abnormalities
- **Aortic regurgitation**
36
Involvement of the digital tendon sheath in reactive arthritis produces what?
**Sausage fingers** or **toes**
37
What is the typical presenation of enteric associated arthritis, joints involved, and how does it differ in course from reactive arthritis?
- Appears **_abruptly_** tends to involve **knees** and **ankles**; sometimes the **wrists, fingers****,**and**toes**
- **Lasts** for about a **year** vs. **reactive arthritis** which wax and wanes for about **6 weeks**
38
Sx's of psoriatic arthritis typically manifest when and predominantly consist of what?
- Between **ages 30-50 y/o**
- Predominantly a **peripheral arthritis** of **hands** and **feet**
- **DIP** joints affected 1st, **asymmmetric** distribution --\> **"pencil in cup"** deformity
39
Gonococcal arthritis has a predilection for which sex; how does the presenation differ from other casuses of suppurative arthritis?
- Mainly **sexually active women**
- Presents in a more **subacute fashion**
40
What is the classic presentation of suppurative arthritis and what are the systemic findings?
- Sudden development of **acutely painful** and **swollen joint** w/ _restricted_ **ROM**
- **Fever** + **leukocytosis** + ↑ **ESR**
41
90% of nongonococcal cases of suppurative arthritis involve how many joints and which joints are most frequently affected?
**Single joint**, _most commonly_ the **knee** \> hip \> shoulder \> elbow \> wrist \> SC joint
42
Pt's with deficiency of complement MAC (C5, C6, C7) are at greater risk for suppurative arthritis from which organism?
Gonoccocal infections
43
How is suppurative arthritis diagnosed?
**Joint aspiration** yielding **purulent fluid** in which **causal agent** is identified
44
Which joints are most often affected in Lyme Arthritis and what is course of the disease?
- Primarily **_large joints_** --\> **knee** \> **shoulder** \> **elbow** and **ankles**
- **1-2 joints** at a time, attacks last **few weeks** to **months**, _migration_ to **new sites**
45
How may lyme arthritis be diagnosed?
- **Spirochetes** identified in joints w/ arthritis in about 25% of cases
- **Serologic testing** for **anti-*Borrelia*** **antibodies**
46
Hyperuricemia is a plasma urate level of what?
**\>6.8 mg/dL**
47
Which syndrome is due to a complete absence of HGPRT interrupting the purine salvage pathway resulting in hyperuricemia?
**Lesch-Nyhan syndrome** --\> **Mental retardation** + **Self-mutilation + 2' gout**
48
Describe the inflammatory response following the precipitation of MSU crystals into joints and contribution to gout.
- **Inflammasome** recognizes crystals --\> activates **caspase-1** ---\> prod. of **IL-1β** ---\> accumulation of **neutrophils** + **MΦ's** in joint
- **Urate crystals** may also _activate_ **complement** --\> **chemotactic** complement byproducts
49
Describe how the solubility of MSU in a joint is modulated by both temperature and the chemical composition of the fluid?
- **Synovial fluid** is _inherently_ a **poorer** solvent for MSU than plasma
- **Lower temp.** of peripheral joints also **favors** precipitation
50
How long does it take a patient with hyperuricemia to typically develop gout?
**20-30 years**
51
What are the 4 distinct morphological changes in gout?
1) Acute arthritis
2) Chronic **tophaceous** arthritis
3) **Tophi** in various sites
4) **Gouty nephropathy**
52
What is the pathognomonic hallmark of gout; where are they seen?
- **Tophi** = large aggregations of urate crystals surrounded by intense inflammatory rx of foreign body **_giant cells_**
- Articular cartilage, ligaments, tendons, and bursae; sometimes soft tissues (earlobes, fingertips) or kidneys
53
Which drug may reduce the excretion of urate and contribute to the development of gout?
**Thiazide diuretics**
54
Which heavy metal toxicity may contribute to gout?
**Lead toxicity** --\> **saturnine gout**
55
Where do MSU crystals deposit in kidney and what are some of the complication which arise with gouty nephropathy?
- Deposit in the **renal medullary interstitium** or **tubules**
- Complications = **uric acid nephrolithiasis** + **pyelonephritis**, particularly when urates induce **urinary obstruction**
- **20%** of **chronic** gout --\> death due to **renal failure**
56
In the final stage of gout progression, chronic tophaceous gout, what will characteristically be seen on radiographs?
**Juxta-articular** _bone erosion_ due to osteo**clastic** bone **resorption** and **loss of joint space**
57
When does gout vs. pseudo-gout typically develop and in whom?
- **Gout** = more common in **men** and **_after_** age **30**
- **Pseudo-gout** = both sexes **equally** affected and occurs in pt's **\>50 y/o** becoming more common w/ ↑ age
58
An autosomal dominant variant of pseudo-gout leading to the development earlier in life is due to germline mutations in what?
**Pyrophosphate transport channel**
59
Secondary form of pseudo-gout is associated with what underlying conditions?
- **Previous joint damage**
- **Hyperparathyroidism**
- **Hemochromatosis**
- **Hypomagnesemia**
- **Ochronosis**
- **Diabetes**
60
What do the crystals of pseudo-gout form and how are they seen histologically?
- Form **chalky, white, friable** deposits
- Seen histologically as **oval blue-purple aggregates**
- Individual crystals are **rhomboid** and **_positively_** birefringent
61
Where is a common location for ganglion cyst's to arise, how to they appear, and arise as a result of what?
- Around **joints** of **wrist**
- **Firm, fluctuant****, pea-sized _translucent_** nodule
- Arise as result of **cystic** or **myxoid degeneration** of CT; hence the **cyst wall** _lacks_ a **cell lining**
62
What is a synovial cyst and what is a common example of one?
- **Herniation** of the synovium thru a **joint capsule** or **massive** enlargement of a bursa
- **Baker cyst** seen in **popliteal space** in setting of **RA**
63
What are common locations to find the diffuse vs. localized type of tenosynovial giant cell tumor; occur in which age group?
- **Diffuse** = tends to involve **large** joints; commonly **knee** (**80%**)
- **Localzied** = usually occurs as discrete nodule attached to tendon sheath, commonly in **_hand_**
- Both occur in pt's **20-40 y/o**; both sexes equally
64
Which reciprocal translocation is seen with tenosynovial giant cell tumors and what does this mutation cause?
- **t(1;2)** ---\> fusion of **type VI collagen α-3** **promoter** upstream of the coding sequence of **M-CSF**
- Leads to **overexpression** of **M-CSF** --\> stimulates **macrophage** proliferation
65
What is the behavior of the localized type of tenosynovial giant cell tumors; how common are they?
- Manifests as **solitary**, **slow-growing**, _painless_ mass that frequently involves **tendon sheaths** along **wrists** and **fingers**
- **_Most common_** mesenchymal neoplasm of **hand**
66
What is characteristic morphology of the diffuse type of tenosynovial giant cell tumor?
Joint synovium converted into **tangled mat** by **red-brown folds** + **finger-like projections** and **nodules**
67
How does the diffuse type of tenosynovial giant cell tumor commonly present?
- Commonly **knee** \> **hip** \> **ankle** \> **calcaneocuboid joints**, pt's typically complain of **_pain_** + **locking** + **recurrent swelling**
- As tumor grows **joint** becomes **stiff** --\> ↓ **ROM**
- Sometimes a **palpable mass** can be appreciated
- **Aggressive tumors** erode into adjacent bones and ST's
