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49 Cards in this Set
- Front
- Back
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What are two common pathological processes which affect joints?
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1. Crystal deposition (MSU or CPPD)
2. Infiltration of synovium by immune active cells |
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What are the structures that are involved in synovial joints?
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- Subchondral bone
- Hyaline cartilage liner - Some have fibrocartilage miniscus - Joint capsule - Synovial lining layer |
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What structure in a synovial joint supports the cartilage and absorbs impacts?
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Subchondral bone
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What structure in a synovial joint provides nearly frictionless joint movement, without a blood supply?
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Hyaline Cartilage Liner
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What structure in some synovial joints can provide stabilization?
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Fibrocartilage Meniscus
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What structure in a synovial joint holds the joint together and provides stability?
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Joint capsule
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What structure in a synovial joint produces joint fluid?
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Synovial lining liner
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What is the typical clinical presentation associated with inflammation (from arthritis)?
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- Morning stiffness > 1 hr
- Erythema and warmth (limited association) - Synovitis (thickening of synovium around joints; tender upon firm palpation) |
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What lab tests are indicative of inflammation (from arthritis)?
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- Inflammatory markers - erythrocyte sedimentation rate (ESR) and C reactive protein (CRP)
- Peripheral blood leukocytosis - Joint fluid analysis (synovial fluid analysis w/ WBC >2000) |
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What radiographic changes are indicative of inflammation (from arthritis)?
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X-ray shows erosions of bone at joint margins
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Regarding uric acid elevations, what is the cause of gout?
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- 10% d/t overproduction of uric acid
- 90% d/t underexcretion of uric acid |
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How prevalent is gout? Males vs females?
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- 4% prevalence (~12 million)
- 1.3 M : 0.5 F - Increase in females after menopause (estrogen promotes urate renal excretion) - Higher in some non-Caucasian groups - More common w/ increased BMI d/t metabolic syndrome |
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What contributes to the amount of uric acid in the body?
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- 1/3 from dietary nucleotides and nucleoproteins
- 2/3 from cellular nucleotides and nucleoproteins (therefore, altering your diet doesn't solve the problem because you still are making uric acid from cells - Nucleotides and nucleoproteins converted to adenine and guanine on route to making uric acid |
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What are the mechanisms of uric acid secretion?
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- 1/3 gut excretion (bacterial degradation, approx. 200 mg/day)
- 2/3 renal excretion (10% of filtered load, approx. 600 mg/day) |
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How big is the uric acid pool in the body?
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~ 1000 mg
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Why is renal excretion of uric acid inefficient?
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1. All serum urate is filtered through glomerulus
2. Proximal tubule resorbs 99% of load 3. Descending tubule: re-secretion of 50% of resorbed load 4. Ascending tubule: resorption of about 80% of re-secreted urate 5. Distal tubule excretes about 10% of filtered load (approx. 600 mg/day) |
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What causes overproduction of uric acid (<10% of gout)?
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- Enzymatic abnormalities
- Increased cell turnover - Diet - Alcohol |
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What causes underproduction of uric acid (>90% of gout)?
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- Metabolic syndrome
- Renal disease - Drugs: diuretics, cyclosporine - Alcohol |
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How do the levels of uric acid correlate to gout occurrence?
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Uric acid / Gout occurrence:
- <6 / 0.9% - 6-6.9 / 2.8% - 7-7.9 / 17.3% - 8-8.9 / 27.5% - >9 / 90% * Gout is more likely if you have more uric acid, but can't rely on amount of uric acid as a test because some have high levels and not gout and vice versa * |
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What is podagra?
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Gout of the foot (especially big toe)
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How is a definitive diagnosis of gout made?
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Identification of monosodium urate (MSU) crystals in synovial fluid or a tophus --> they demonstrate birefringence meaning that polarized light on crystals should change from yellow to blue (or vice versa) depending on polarization
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What happens to monosodium urate (MSU) crystals?
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Phagocytosed by neutrophils
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What does polyarticular gout mean?
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It affects more than one joint (usually takes years)
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What is tophaceous gout?
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Nodular masses of uric acid crystals (tophi) deposited in different soft tissue areas of the body; can cause punched out bone lesions and overhanging edges
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What precipitates a gout attack?
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- Elevation of uric acid
- Reduction of uric acid - Release of crystals from pre-formed deposits |
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What are the steps of the inflammatory cascade in gout?
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1. Recognition of monosodium urate crystals by phagocytic cell
2. Phagocytosis of MSU crystals 3. Inflammasome activation 4. Release of IL-1beta 5. Signal transduction 6. Pro-inflammatory response 7. Neutrophil recruitment 8. More release of IL-1beta |
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What is the inflammasome?
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- Multi-protein complex that promotes maturation of inflammatory cytokines IL-1beta, IL-18, IL-33 (important for gout inflammation)
- 3 parts: nalp3, asc, and pro-caspase-1 |
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How common is Calcium Pyrophosphate Dihydrate deposition disease (CPPD)?
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~12% of elderly (5% at age 60, rising to >30% by age 90)
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What is the etiology behind Calcium Pyrophosphate Dihydrate deposition disease (CPPD)?
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Unknown, but in most cases related to overproduction of pyrophosphate (PPi)
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Calcium Pyrophosphate Dihydrate (CPPD) crystals can be found in what context?
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CPPD crystals may be found w/ urate crystals ("mixed crystals")
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What happens to Calcium Pyrophosphate Dihydrate (CPPD) crystals?
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Phagocytosed by neutrophils
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What are some chemistry abnormalities associated with Calcium Pyrophosphate Dihydrate deposition disease (CPPD)?
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- Hemochromatosis (iron overload)
- Hypophosphatasia (Alk phos) - Hypomagnesimia (Mg) - Hyperparathyroidism (low Ca2+) |
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What is "Pseudogout"? Symptoms?
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- Calcium Pyrophosphate Dihydrate deposition disease (CPPD)
- Attacks of acute arthritis similar to gout, but usually in larger joints: knee, wrist, shoulder - Commonly asymptomatic - May be associated with widespread Osteoarthritis (OA), including OA in atypical joints - May be RA-like (MCP joint enlargement) - may produce chronic low grade inflammation |
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How do you diagnose Calcium Pyrophosphate Dihydrate deposition disease (CPPD) / "Pseudogout"?
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- Rhomboidal shaped, positively birefringent crystals in joint fluid (polarized light on crystals should change from yellow to blue (or vice versa) depending on polarization)
- X-ray: suggested by chondrocalcinosis (but not in all cases) |
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What kind of disease is Rheumatoid Arthritis?
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- Immunological (T cell) disease, but w/ significant B cell contribution
- Invasion by immune lineage cells, but w/ recruitment of local cells (synovial fibroblasts) - Proliferation of synovium (synovitis) w/ characteristics of a benign, locally invasive tumor |
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What factors contribute to getting Rheumatoid Arthritis?
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- Genetics (e.g., HLA-DR "shared epitope")
- Hormonal (F > M) - Environmental (e.g., smoking) |
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What are the symptoms in a joint affected by Rheumatoid Arthritis?
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- Inflamed synovial membrane
- Pannus: contains T cells / macrophages, also fibroblasts, plasma cells, endothelium, and dendritic cells - Synovial fluid contains neutrophils - Cartilage thinning |
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What is rheumatoid factor?
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IgM directed against Fc portion of IgG
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What is Anti-Cyclic Citrullinated Peptide (CCP)? When is it seen?
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- Protein that can be used to detect RA
- Seen in early RA (rheumatoid factor negative) - Positive in some cases of rheumatoid factor negative RA - Correlates w/ overall disease activity |
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How does testing for Rheumatoid Factor (RF) compare to Anti-Cyclic Citrullinated Peptide (CCP)?
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- CCP has the same sensitivity as RF, but more specific
- Fewer false positives (25%) |
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What is the common presentation of Rheumatoid Arthritis?
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- Osteoporosis
- Erosions - Subluxation |
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What are the 3 most important criteria for Rheumatoid Arthritis?
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* At least 3 swollen joints
* Wrist, MCP, PIP involvement * Rheumatoid nodules - AM stiffness > 1hr - Symmetrical arthritis - Positive Rheumatoid Factor - X-ray change typical of RA in hand/wrist - Need 4/7 > 6 weeks |
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What disease is associated with periodontitis?
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- Rheumatoid arthritis (patients almost 2x as likely as osteoarthritis to have mod-severe periodontitis)
- Share genetic risk - HLA DRB1 - Share smoking risk - Anti-CCP antibodies found more often in both (citrullinated peptides made by enzyme PAD that is found in prokaryote associated w/ PD - if you have these Abs you may get dz?) |
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What is periodontitis?
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Inflammation of the tissue around the teeth, often causing shrinkage of the gums and loosening of the teeth.
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How common is periodontitis in general?
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20% of Western populations
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What is the cause of Periodontitis?
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- Porphyromonas gingivalis found in PD
- Contains enzyme Peptidyl Arginine Deiminase (PAD) - PAD converts arginine to citrulline - PAD citrullinates a number of peptides, making neo-epitopes - Genetically predisposed persons form Abs to citrullinated peptides (anti-CCP) --> Perhaps initiates / perpetuates RA |
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Is there a familial association with rheumatoid arthritis?
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Uncommon, but some families have multiple affected members
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What are the systemic symptoms associated with rheumatoid arthritis?
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- Sicca symptoms: no tears or saliva (dry eyes and mouth)
- Risk factor for CV dz (equal to DM) - RA lung involvement (pleuritis w/ effusion, interstitial fibrosis, nodules, Caplan's syndrome - pneumoconiosis) - GI side effects d/t NSAID use - Hand numbness (CTS) and neuropathy - Vasculitis |
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What is the association between CV disease and RA?
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- Increased risk of CV dz w/ RA
- Inflammation mediated atherosclerosis |
