NMSP 3 > Chapter 26: Joints > Flashcards

Chapter 26: Joints Flashcards

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1
Q

What are the 3 major components of hyaline cartilage?

A

70% H2O + 10% type II collagen + 8% proteoglycans

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2
Q

Which joints are most commonly affected in osteoarthritis in men vs. women?

A
  • Men = hips
  • Women = hands and knees
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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
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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
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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)
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6
Q

Deep, achy pain that worsens with use, morning stiffness, crepitus, and limitation of ROM is characteristic of what?

A

Osteoarthritis

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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
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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
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9
Q

OA is a disease of what vs. RA?

A
  • OA = disease of cartilage
  • RA = disease of synovium
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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

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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
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12
Q

Which cytokine has been most firmly implicated in the pathogenesis of RA?

A

TNF

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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)

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14
Q

What are 2 genetic factors associated with RA?

A

HLA-DRB1 alleles & PTPN22 gene

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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
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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

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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

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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.
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19
Q

Where are rheumatoid nodules most commonly seen?

A

Extensor surfaces at pressure points

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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
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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
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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

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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
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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
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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
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