(I) General Concepts

Question 1

ACR choosing wisely

Answer 1

1. Do not test antinuclear antibody (ANA) subserologies (anti-dsDNA, anti-Sm, anti-RNP, anti-SS-B,
   anti-Scl-70) without a positive ANA and clinical suspicion of immune-mediated disease. Anti-SS-A
   may be an exception to this recommendation.
2. Do not test for Lyme disease as a cause of musculoskeletal symptoms without an exposure history and
   appropriate examination findings.
3. Do not perform an MRI of the peripheral joints to routinely monitor inflammatory arthritis.
4. Do not prescribe biologics for RA before a trial of methotrexate (or other conventional nonbiologic
   disease-modifying antirheumatic drugs [DMARDs]).
5. Do not routinely repeat dual-energy X-ray absorptiometry (DXA) scans more often than once every 2 years.

Question 2

ACR peds choosing wisely

Answer 2

1. Do not order autoantibody panels without a positive ANA and evidence of a rheumatic disease.
2. Do not test for Lyme disease as a cause of musculoskeletal symptoms without an exposure history and
   appropriate examination findings.
3. Do not routinely perform surveillance joint radiographs to monitor juvenile idiopathic arthritis (JIA)
   disease activity.
4. Do not perform methotrexate toxicity laboratory tests more than every 12 weeks on stable doses.
5. Do not repeat a confirmed positive ANA in patients with established JIA or SLE.

Question 3

NASS choosing wisely

Answer 3

• Do not order MRI of the spine within the first 6 weeks in patients with nonspecific low back pain in the
absence of red flags (trauma, use of corticosteroids, unexplained weight loss, progressive neurologic signs,
age >50 years or

Question 4

Do NOTS

Answer 4

• Except for anti-dsDNA, do not repeat ANA subserologies in patients with an established connective
tissue disease (CTD) diagnosis.
• Do not perform serial measurements of rheumatoid factor and anti-cyclic citrullinated peptide (CCP) in
patients with documented seropositive RA or serial ANAs in patients with a documented positive ANA
and a CTD diagnosis (e.g., SLE).
• Do not order a human leukocyte antigen (HLA)-B27 unless you suspect an undifferentiated spondyloarthropathy
based on history and examination but have nondiagnostic radiographs.
• Do not check CH50 to follow lupus disease activity.
• Do not order an MRI before ordering plain films in a patient presenting with joint or back pain.
• Do not use intraarticular hyaluronic acid injections for advanced knee OA (i.e., bone on bone).
• Do not treat low bone mass in patients at low risk for fracture (T score > –2.5, no history of fragility
fracture, no steroids, low FRAX).
• Do not order serial yearly plain radiographs in a patient with good clinical (symptoms, examination,
laboratory tests) control of their arthritis unless you are willing to change therapy for minor radiographic
disease progression.

Question 5

Soft tissue rheumatism.

Answer 5

• Most shoulder pain is periarticular (i.e., a bursitis or tendinitis). Rule out impingement in patients with recurrent
shoulder tendinitis.
• Causes of olecranon or prepatellar bursitis: trauma, infection, gout, rheumatoid arthritis (RA).
• Recalcitrant trochanteric bursitis: rule out leg length discrepancy, hallux rigidus with an abnormal gait,
and lumbar radiculopathy.
• Recalcitrant medial knee pain: rule out anserine bursitis.
• Recalcitrant patellofemoral syndrome: rule out pes planus/hypermobility causing patellar maltracking.
• Due to risk of rupture, do not inject corticosteroids for therapy of Achilles tendinitis/enthesitis.
Use iontophoresis.

Question 6

3. Back pain.

Answer 6

• Patients with significant low back pain cannot do a sit-up.
• Most back pain is nonsurgical.
• Magnetic resonance imaging (MRI)/computed tomography (CT) scans of lumbar spine are abnormal in
30% of patients with no symptoms. Do not attribute a patient’s symptoms to an abnormal radiograph.
• Spinal Phalen’s test is useful to diagnose spinal stenosis. Patients with spinal stenosis have more pain
walking uphill due to spinal extension making the spinal canal smaller. Straight leg raise test and
electromyography/nerve conduction velocities (EMG/NCV) are often normal or nonspecific.

Question 7

Labs

Answer 7

5. Laboratory tests
   • Laboratory tests should be used to confirm your clinical diagnosis not make it.
   • All patients with a positive rheumatoid factor do not have RA, and all patients with a positive antinuclear
   antibody do not have systemic lupus erythematosus (SLE).
   • Low complement (C3, C4) levels in a patient with systemic symptoms suggest an immune complexmediated
   disease and narrows your diagnosis: SLE, cryoglobulinemia (types II and III), urticarial vasculitis
   (HepB and C1q autoantibodies), subacute bacterial endocarditis (SBE), poststreptococcal or membranoproliferative
   glomerulonephritis.
   • An undetectable (not just low) CH50 activity may indicate a disease associated with a hereditary complement
   component deficiency: autoimmune (C1, C4, C2), infection (C3), Neisseria infection (C5 to C8).
   • Separating iron deficiency from anemia of chronic disease is best done by measuring the ferritin level. In a
   patient with elevated C-reactive protein, a ferritin level of >100 ng/mL rules out iron deficiency.

Question 8

chronic inflammatory monoarticular arthritis of >8 weeks’ duration

Answer 8

synovial biopsy to rule out

an unusual cause (indolent infection, etc.).

Question 9

Feel both knees with the back of your hand for temperature differences and compare it to the
lower extremity.

Answer 9

The knee should be cooler than the skin over the tibia. If the knee is warmer then there is ongoing knee
inflammation.

Question 10

OA

Answer 10

• Cracking knuckles does not cause OA.
• Patients with arthritis can predict the weather due to changes in barometric pressure as weather fronts
move in and out of an area.
• Obesity is the major modifiable risk factor for OA.
• The joints typically involved in primary OA are: distal interphalangeal joints (DIPs) (Heberden’s nodes),
proximal interphalangeal joints (PIPs) (Bouchard’s nodes), first carpometacarpal (CMC), hips, knees, first
metatarsophalangeal joint (MTP), the cervical and lumbosacral spine.
• Patients with OA affecting joints not normally affected by primary OA (i.e., metacarpophalangeals,
wrists, elbows, shoulder, ankles) need to be evaluated for secondary causes of OA (i.e., calcium pyrophosphate
disease [CPPD], metabolic diseases, others).
• Erosive OA is an inflammatory subset of OA (10% of patients) primarily affecting the hands (DIPs, PIPs,
first CMC) and causing the “seagull” sign on radiographs. It is more disabling than primary OA

Question 11

Knee and hip osteoarthritis

Answer 11

• Over 50% of patients over 65 years have radiographic knee OA but only 25% have symptoms. Do not rely
on the radiograph to make the diagnosis of the cause of knee pain.
• Recurrent, large, noninflammatory knee effusions are frequently due to an internal derangement
(e.g., meniscal tear).
• Nonsteroidal antiinflammatory drugs (NSAIDs) are better than acetaminophen if a patient has an
effusion, which indicates more inflammation (wet OA).
• Intraarticular corticosteroids also work and are cheaper than viscosupplementation (hyaluronic acid),
especially in patients with a knee effusion.
• Drain any knee effusion before giving viscosupplementation or corticosteroids.
• Incidental and asymptomatic meniscal tears are common (>20%) in patients with knee OA. Meniscal
repair and/or arthroscopic debridement and washout are not helpful unless there are signs of locking.
• Femoroacetabular impingement is a common cause of hip pain in young patients who develop early OA.

Question 12

Seronegative RA is a difficult diagnosis in patients without erosions on radiographs

Answer 12

Always consider CPPD in these patients.

Question 13

Treat to target

Answer 13

Early therapy with the goal of low disease activity is essential to RA (and psoriatic arthritis) therapy.
• It does not matter which disease activity measure you use (e.g., Clinical Disease Activity Index [CDAI],
Routine Assessment of Patient Index Data 3 [RAPID3], etc.), just pick one and use it to document if your
therapy is achieving low disease activity or remission.

Question 14

Systemic sclerosis.

Answer 14

• New onset hypertension and schistocytes on blood smear in a diffuse systemic sclerosis patient heralds
the onset of scleroderma renal crisis, especially in a patient who is anti-RNA polymerase III positive.
Angiotensin-converting enzyme (ACE) inhibitors work better than angiotensin receptor blockers (ARBs).
• A %forced vital capacity (FVC)/%DLCO ratio of >1.6 predicts pulmonary hypertension.
• An FVC <70% and a high resolution CT scan of the lung showing >20% fibrosis predicts progression of
scleroderma-related interstitial lung disease.

Question 15

36. Statins can cause myalgias without an elevated CPK, myalgias with an elevated CPK, and a
    necrotizing myopathy with anti-HMGCoA reductase antibodies.

Answer 15

• Myalgias can be improved with coenzyme Q.

* Hydrophilic statins (pravachol, rosuvastatin) cause less myopathy than lipophilic statins (simvastatin, etc.).

Question 16

Hydrophilic statins

Answer 16

pravachol, rosuvastatin

Question 17

lipophilic statins

Answer 17

simvastatin, etc

Question 18

APL labs:

Answer 18

lupus anticoagulant,
anticardiolipin antibodies,
anti-β2glycoprotein I antibodies

Question 19

All patients with significantly positive aPLabs should have prophylactic anticoagulation if they
undergo a surgical procedure and/or following pregnancy delivery even if they have never had
a clot.

Answer 19

Surgical release of tissue factor is the second hit in the “two hit” hypothesis for clots in aPLab positive patients.
• Always have placenta assessed (clinically and/or pathologically) for evidence of damage in patients with
aPLab regardless of pregnancy outcome. If placental damage is present, the patient needs anticoagulation
during any future pregnancy.

Question 20

Still’s disease should be considered in any patient with a quotidian fever (decreases to normal
or below once a day), rash, and joint pain.

Answer 20

A ferritin level >1000 ng/mL supports the diagnosis.

Question 21

(PMR) patients should respond completely to 20 mg daily of
prednisone
and normalize their erythrocyte sedimentation rate (ESR) within a month

Answer 21

The presence of fever or failure to respond to prednisone clinically and serologically suggests giant cell
arteritis or another diagnosis such as lymphoma.

Question 22

After ruling out infection and malignancy, consider vasculitis in any patient with multisystem
disease who has an ESR >100 mm/hour and a C-reactive protein >10 times the upper limit of
normal.

Answer 22

• The primary vasculitides (i.e., not due to another disease) are not associated with positive serologies
(ANA, rheumatoid factor (RF), low complements), neutropenia, or thrombocytopenia. If one of these are
present, consider another diagnosis.

Question 23

Listen for subclavian bruits in all patients suspected of having GCA as it may be their only
clinical
finding

Answer 23

Large vessel involvement puts them at increased (17×) risk for aortic dissections and aneurysms.

Question 24

Do not delay starting prednisone in a patient suspected to have GCA

Answer 24

GCA.

It will not affect the temporal artery biopsy results for at least a week.

Question 25

When the suspected diagnosis is primary vasculitis of the central nervous system (CNS), it
probably is incorrect

Answer 25

Rule out other diseases with a brain biopsy

Question 26

GPA or Wegener’s) should be considered in any adult who

develops otitis media.

Answer 26

GPA predominantly affects the upper and lower respiratory tracts and kidneys and is associated with
proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA).

Question 27

Skin biopsy in Henoch–Schonlein purpura (HSP) shows leukocytoclastic vasculitis with IgA
deposition in vessel walls on direct immunofluorescence

Answer 27

HSP is the most common small vessel vasculitis in childhood.

Question 28

Most patients with mixed cryoglobulinemia will present with palpable purpura, arthralgia, and
weakness/myalgias (Meltzer’s triad).

Answer 28

A positive rheumatoid factor and low C4 (“poor man’s cryo”) level supports the diagnosis before the
cryoglobulin
screen has returned.

Question 29

Meltzer’s triad

Answer 29

palpable purpura, arthralgia, and
weakness/myalgias

(ptx with mixed cryo)

Question 30

Even though HLA-B27 increases a person’s risk of developing a spondyloarthropathy 50 times,
only 1 out of every 50 (2%) HLA-B27 positive individuals without a family history will develop
ankylosing spondylitis during their lifetime

Answer 30

If the person has a family history the risk increases to one in five (20%).
• Nearly 50% of HLA-B27 positive patients with recurrent unilateral anterior uveitis have or will develop
an underlying spondyloarthropathy

Question 31

A patient less than 40 years old with three out of four of the following has a high likelihood of
having inflammatory back pain:

Answer 31

(1) morning stiffness of at least 30 minutes; (2) improvement of
back pain with exercise but not rest;
(3) awakening because of back pain and stiffness during
second half of the night only;
(4) alternating buttock pain.

Question 32

60. Inflammatory arthritis is most likely to occur in Crohn’s disease patients with extensive colonic
    involvement

Answer 32

These patients may present with prominent arthritis but few gastrointestinal symptoms

Question 33

62. Reactive arthritis is a sterile, inflammatory arthritis that is typically preceded by a gastrointestinal
    or genitourinary infection occurring 1 to 4 weeks previously.

Answer 33

The arthritis can improve with prolonged antibiotics only if it is due to chlamydia

Question 34

Inflammation of the DIP joints and finger dactylitis are highly characteristic of psoriatic arthritis.

Answer 34

• Differential diagnosis of DIP arthritis: psoraitic, OA, multicentric reticulohistiocytosis, and primary biliary
cirrhosis. In a patient with OA who gets inflamed DIP–R/O gout.

Question 35

• Differential diagnosis of DIP arthritis:

Answer 35

psoraitic, 
OA, 
multicentric reticulohistiocytosis, 
primary biliary cirrhosis. 
In a patient with OA who gets inflamed DIP–R/O gout.

Question 36

64. Any patient with fever, arthralgias, and tenosynovitis should be evaluated for a disseminated
gonococcal infection (DGI).

Answer 36

The majority of females develop DGI within 1 week of onset of menses.

Question 37

66. The chest radiograph is normal in 50% of patients who have tuberculous septic arthritis, which
    most commonly presents as chronic inflammatory monoarticular arthritis involving the knee

Answer 37

diagnosis of tuberculous arthritis is best confirmed by synovial biopsy and culture because synovial fluid
acid fast bacilli (AFB) stain is positive in only 20%

Question 38

68. Hepatitis C is the most common cause of cryoglobulinemia

Answer 38

Overall, 50% of hepatitis C patients have cryoglobulins, but only 5% develop cryoglobulinemic vasculitis

Question 39

69. Gout is the most common cause of inflammatory arthritis in men over age 40 years

Answer 39

It should not occur in premenopausal females

Question 40

Uric acid is less soluble in the cold.

Answer 40

Consequently, gout occurs in the cooler distal joints and not in the spine or joints near the spine. If you do
not get any fluid when you tap the first MTP joint, blow out the end of the needle onto a slide and examine
the blood speck for uric acid crystals.

Question 41

CPPD disease is a disease of the elderly with onset and increasing frequency after the age of
55 years.

Answer 41

Only patients with familial mutations or metabolic abnormalities (e.g., hemochromatosis, hypophosphatasia,
etc.) get CPPD before age 55 years.

Question 42

CPPD before age 55 years.

Answer 42

familial mutations or metabolic abnormalities (e.g., hemochromatosis, hypophosphatasia,

Question 43

73. CPPD should be considered in any elderly patient with a seronegative inflammatory or degenerative
    arthritis involving the MCPs, wrists, and shoulders.

Answer 43

CPPD can mimic seronegative RA, PMR, and OA involving atypical joints.

Question 44

Osteoporosis

Answer 44

major risk factors for fragility fractures are low bone mass, advancing age, previous fragility fractures,
corticosteroid use, and the propensity to fall. The best predictor of a future fall is a fall within the previous
6 months. Screen the patient with the “get up and go” test.
• Each decrease of –1.0 T-score on DXA correlates with a 12% loss of bone. At a T-score of –2.5, the patient
has lost 30% of their bone mass, which is when osteopenia can reliably be detected on plain radiographs.
• Rule out vitamin D insufficiency in all patients with a low bone mass. Consider celiac disease in any Caucasian
patient with a low vitamin D level even if they do not have diarrhea.
• Pharmacological therapy should be initiated in patients who have had a fragility fracture, a bone
mineral density T-score ≤–2.5, or a FRAX-derived 10-year risk of ≥3% for hip fractures and ≥20%
for other major osteoporosis fractures.
• Vertebroplasty and kyphoplasty are most effective when done within 6 months of onset of a severely
symptomatic vertebral compression fracture and in patients with vertebral edema pattern on MRI.
• Stress fracture should be considered when new onset lower extremity bone pain (tibia, fibula, metatarsal)
is increased by the vibration of a tuning fork (128 Hz) (sensitivity and specificity >80%).

Question 45

80. Musculoskeletal manifestations can be the presenting manifestation in up to 33% of patients
    with hemochromatosis.

Answer 45

Consider in any Caucasian male under age 40 years with “seronegative RA,” degenerative changes of the
second and third MCP joints, and/or hypogonadotrophic hypogonadism with low bone mass

Question 46

Fibromyalgia is a chronic noninflammatory, nonautoimmune central afferent processing disorder
leading to a diffuse pain syndrome as well as other symptoms.

Answer 46

Narcotics and corticosteroids should not be used for treatment.

Question 47

Obstructive sleep apnea (ask if they snore even if they are nonobese), hypothyroidism, and
vitamin D deficiency (25 OH vitamin D <5 ng/mL) should be ruled out in all fibromyalgia patients
regardless of body size.

Answer 47

In patients with severe and refractory symptoms, ask about physical and/or sexual abuse.

Question 48

Growing pains do not occur during the daytime.

Answer 48

A limp in a child is pathologic until proven otherwise.

Question 49

Consider Kawasaki disease in any child under age 5 years presenting with prolonged high
fevers and conjunctivitis.

Answer 49

Intravenous immunoglobulin (IVIG) within 10 days of disease onset is the treatment of choice

Question 50

Muscle cramps, pain, or myoglobinuria brought on by exercise suggests a metabolic myopathy.

Answer 50

Muscle symptoms with short bursts of high-intensity exercise and the second wind phenomenon are characteristic
of a glycogen storage disease. McArdle’s disease and acid maltase deficiency are most common.
• Muscle symptoms with prolonged low-intensity exercise and/or prolonged fasting suggests a defect in fatty
acid oxidation. Carnitine palmitoyltransferase II (CPT II) deficiency is most common.
• The most common metabolic myopathies associated with myoglobinuria are CPT II deficiency and
McArdle’s disease.
• The most common myopathies that are confused with polymyositis are acid maltase deficiency and
limb-girdle muscular dystrophy.
• Children presenting with a muscle disease without rash almost always have a metabolic or genetic myopathy
and not primary polymyositis.

Question 51

characteristic

of a glycogen storage disease

Answer 51

Muscle symptoms with short bursts of high-intensity exercise and the second wind phenomenon
McArdle’s disease and acid maltase deficiency are most common.

Question 52

fatty

acid oxidation

Answer 52

Muscle symptoms with prolonged low-intensity exercise and/or prolonged fasting

Carnitine palmitoyltransferase II (CPT II) deficiency is most common

Question 53

A patient with acute, inflammatory arthritis involving bilateral ankles should always be evaluated
for sarcoidosis.

Answer 53

Erythema nodosum typically affects the anterior aspect of lower legs and never ulcerates. Subcutaneous
nodules on the posterior aspect of calf or any that ulcerate should raise concern for vasculitis or infection.

Question 54

Autoinflammatory syndromes are characterized by episodes of fever, rash, arthritis, peritonitis,
eye inflammation, lack of autoantibodies, and elevated acute phase reactants in various combinations
that normalize between flares.

Answer 54

The duration of flares differs between diseases:
TRAPS > HIDS > FMF > MWS/FCAS.

Inhibition of
interleukin-1 is the treatment of choice.

Question 55

Medications.

• Always rule out a medication as the cause of musculoskeletal symptoms.

Answer 55

— pANCA vasculitis: 
hydralazine, 
propylthiouracil, 
minocycline, 
cocaine (levamisole).

— Achilles tendinitis and rupture.
Fluoroquinolones:

— Drug-induced lupus: 
hydralazine, 
minocycline, 
anti-TNF agents, 
rifabutin, 
procainamide,

Question 56

• All NSAIDs should be used with caution (if at all) in patients with:

Answer 56

underlying renal or cardiovascular

disease.

Question 57

All NSAIDs can cause:

Answer 57

photosensitivity. Piroxicam is most likely to cause small bowel webs

AND can interfere with conception

Question 58

AVN from corticosteroids is the most common reason a physician is sued for a medication
adverse effect.
Record in the chart that you counseled the patient on the following risk:

Answer 58

for each 20mg of prednisone taken for over a month, the risk of AVN is 5% (e.g., a 60-mg dose for a month confers
a risk of 15% for AVN).
Patients with SLE, those that have aPLabs, and those that rapidly become cushingoid
are most at risk.

Question 59

Methotrexate is the most effective anchor drug for all combination therapies. An increase of the:

Answer 59

mean corpuscular volume by 5 fL correlates with a good methotrexate effect.

Question 60

Azathioprine is better used for maintenance of remission than for induction of remission. It should NOT be used in patients:

Answer 60

on allopurinol,
febuxostat,
ampicillin (rash).

It can cause resistance to coumadin
effectiveness

Question 61

HLA-B*5801 gene.

Answer 61

Allopurinol hypersensitivity syndrome is more common in Asian patients with kidney disease

Question 62

Do not use colchicine:

Do not use in patients on clarithromycin who have renal
insufficiency.

Answer 62

in ptx who are on

• cyclosporine/tacrolimus (causes myopathy),
• antifungals(e.g., ketoconazole),
• HIV protease inhibitors.

in patients on clarithromycin who have renal
insufficiency.

Question 63

check what before Pegloticase ??

Answer 63

G6PD status

Question 64

Stop ACE inhibitors in patients with:

Answer 64

chronic regional pain syndrome

Question 65

stop calcium channel blockers in:

Answer 65

patients with erythromelalgia.

Question 66

Voriconazole can cause:

Answer 66

nodular hypertrophic osteoarthropathy.

Question 67

A properly fitted cane

Answer 67

used in the contralateral hand can unweight a diseased hip by 25% to 40%.

Question 68

Up to heaven, down to hell

Answer 68

When a patient has a painful lower extremity joint, tell him/her to use the
good leg to step up a stair (up to heaven) and use the painful leg to step down a stair (down to hell).

Question 69

two indications for joint replacement surgery

Answer 69

(1) pain unresponsive to medical therapy and
(2) loss of joint function. Therefore, inability to walk more than one block, stand longer than 20 to 30
minutes due to pain, or walk up stairs are indications for total hip and total knee replacement

Question 70

Lumbar spine surgery is most successful in patients

Answer 70

Lumbar spine surgery is most successful in patients with radicular symptoms confirmed by clinical examination,
EMG, and MRI findings who have failed conservative therapy. Success of surgery decreases by
33% for each one that does not confirm the other.

Question 71

1. what is the most abundant protein in the body?
2. what is the major cartilage of diarthroidial joints?.
3. selective transudate of plasma?.
4. The most critical signaling pathway is a for osteoblast activation and bone mass regulation?
5. The most critical signaling pathway for osteoclast differentiation/activation and bone remodeling?

Answer 71

1. Collagen -Mutations of collagen types I and II can lead to musculoskeletal
   disorders.
2. Hyaline cartilage -It is avascular and aneural and composed mainly of type II
   collagen and aggrecan.

3.Synovial fluid. It is made viscous by the secretion of hyaluronic acid by synoviocytes
into the synovial fluid.

4. Wnt/β-catenin
5. RANKL/RANK/OPG

Question 72

major

macromolecular “building blocks” of connective tissue.

Answer 72

Collagen,
elastin
adhesins,
proteoglycans.

Question 73

How many types of collagen are there?

Answer 73

The collagens are the most abundant body proteins and account for 20% to 30% of the total body mass.

There are at least 29 different types of collagen.

Question 74

definitive structural feature of all collagen molecules

Answer 74

triple helix.

three polypeptide chains (α-chains) twisted around each other into a right-handed major helix

Question 75

major collagen classes and the types of collagen included in each class

Answer 75

Fibril-forming (interstitial)
Fibril-associated collagens with interrupted triple helices (FACIT

Collagens with specialized structures or functions:
Basement membrane collagen—type IV.
Nonfibrillar collagens—types VI, VII, XIII, XV, XVII, XVIII.
Short-chain collagens—types VIII, X.

Question 76

How are the fibril-forming (interstitial) collagens synthesized?

Page 17

Answer 76

30 distinct genes that encode the various collagen chains. In adults, collagen gene expression
is subject to positive regulation (TGF-β) and negative regulation (IFN-γ and TNF-α).

Question 77

Which enzymes are important in collagen degradation? How are they regulated?

Answer 77

important collagenolytic enzymes responsible for cleavage of type I collagen belong to the matrix
metalloproteinase (MMP) group. The collagenases are secreted in latent form and, when activated, cleave
the collagen molecule at a single specific site following a glycine residue located about three quarters of the
distance from the amino terminal end (between residues 775 and 776 of the α1[I] chain). Gelatinases and
stromelysins then degrade the unfolded fragments.Both α-macroglobulin and tissue inhibitors of metalloproteases (TIMP 1 to 4) are capable of inhibiting collagenase
activity. It is likely that other collagen types have type-specific collagenases capable of degrading them.
Serum procollagen peptides, urinary hydroxyproline, urinary pyridinoline/deoxypyridinoline cross-links, and
serum C-telopeptides and urinary N-telopeptides are used as measures of collagen turnover

Question 78

What is elastin, and where is it located?

Answer 78

Elastin fibers are connective tissues that can stretch when hydrated and return to their original length after
being stretched. They are synthesized by smooth muscle cells and less so by fibroblasts. They comprise a significant
portion of the dry weight of ligaments (up to 70% to 80%), lungs, larger blood vessels such as aorta (30%
to 60%), and skin (2% to 5%). Elastin is a polymer of tropoelastin monomers, which contain 850 amino acids,
predominantly valine, proline, glycine, and alanine. When tropoelastin molecules associate to form a fiber,
lysine residues cross-link by forming desmosine and isodesmosine, which are unique to elastin. Mutations in
the elastin gene can cause cutis laxa and supravalvular aortic stenosis. Elastases, which are serine proteases,
are capable of degrading elastase. Elastases are located in tissues, macrophages, leukocytes, and platelets. Such
elastases may contribute to blood vessel wall damage and aneurysm formation in the vasculitides. Urinary
desmosine levels are used as a measure of elastin degradation

Question 79

What are fibrillin-1 and fibrillin-2?

Answer 79

These fibrillins are large glycoproteins coded for by a gene located on chromosome 15 (fibrillin-1) and chromosome
5 (fibrillin-2). They function as part of the microfibrillar proteins, which are associated with an elastin
core. Fibrillin can also be found as isolated bundles of microfibrils in skin, blood vessels, and several other
tissues. Abnormalities in fibrillin-1 are thought to cause Marfan’s syndrome (see also Chapter 55), whereas
abnormalities in fibrillin-2 cause contractural arachnodactyly.

Question 80

List NB adhessins (cell-binding glycoproteins) that can be present in intracellular
matrices and basement membranes.

Answer 80

Fibronectin—connective tissue.
Laminin—basement membrane.
Chondroadherin—cartilage.
Osteoadherin—bone.
These glycoproteins have specific adhesive and other important properties. They bind cells by attaching to
integrins on cells. Some have the classical arginine–glycine–aspartic acid (RGD) cell-binding sequence.