Tuesday: Crystal-induced arthritides Flashcards
(27 cards)
Describe basis pathogenesis of gout.
Acute, intermittent arthritis secondary to monosodium urate (MSU) crystal-induced inflammation.
Urate is…
Intermediate metabolite catabolized by uricase in the elimination of excess nucleic acid purines and nitrogenous waste products through production and exretion of allantoic acid.
Man lacks enzyme uricase (uric acid is end product requiring excretion).
Gout is disease of man.
Pathogenesis of hyperuricemia in gout?
Endogenous overproduction of urate.
Increased availability of PRPP, glutamine, and increased activity of controlling enzyme PRPP aminotransferase==>All lead to urate overproduction.
What is Lesch-Nyhan syndrome?
Decreased or absent activity of HGPRTase. Salvages purine bases that would otherwise be converted to urate in normal person.
Decreased or absent activity leads to more urate production.
Primary vs secondary hyperuricemia
Primary: Idiopathic or inborn error of metabolism leading only to hyperuricemia
Secondary: Acquired or inborn error of metabolism leading to spectrum of diseases (i.e. gout).
Patients with primary gout have what wrong with their kidney?
Defect in renal excretion of urate (40% less urate in urine)
Small number of patients with gout have underlying secondary hyperuricemia. What are some possible causes of this?
Nucleic acid turnover (myeloproliferative diseases)
Acquired renal disease leading to underexcretion of uric acid.
Certain inborn errors of metabolism (Lesch-Nyhan syndrome and von Gierke’s disease
Lead nephropathy (moonshine drinkers) Saturnine gout.
What is earliest path finding in natural history of gout?
Deposition of MSU crystals in synovial and periarticular tissue.
Microtophi are?
Deposits in gouty joints.
What causes microtophus formation:
Reduced solubility of MSU at periphery of the body because of lower temperatures; recurrent trauma; differential ultrafiltration of urate and water from pressure of weight-bearing; genetic/age alterations in binding affinity or urate to glycoproteins in connective tissue matrix.
If crystals are freed into joint space rapidly by physical or metabolic changes (trauma, microfractures, tissue necrosis, rapid dissolution of tophi) then…
Inflammatory arthritis starts!
MSU crystals promote inflammation by…
Electrostatic interactions: Proteins in synovial fluids adsorb to surface of MSU crystals. IgG is bound in a way that promotes adherence/phagocytosis. C1, C3, C4 are also bound.
Can gout cause a polyarticular arthritis?
Yes! It can be without podagra (gout of first metatarsophalangeal joint).
What ages does gout affect?
Between 30-50
Symptoms from renal stones precede arthritis in what percentage of patients with gout?
50%
What is finding is needed for diagnosis of gout?
Plane polarized light microscopy: Negatively birefringent, needle-shaped MSU crystals engulfed by polymorphonuclear leukocytes in synovial fluid aspirate.
What is one important thing to remember about crystals found in joint?
Extracellular crystals persist in synovial fluid for years after an attack with acute gouty arthritis.
Less satisfactory diagnosis: Clinical picture plus response to standard therapeutic regimen. Rapid destruction of gouty joint can lead to crystalline deposits in synovial fluid.
Is elevated serum uric acid level diagnostic of gout?
No.
Leukocytosis, elevated erythrocyte sedimentation rate, shift to more immature PMNs, and presence of serum acute phase reactants (lab correlates of infectious arthritis) may be present in acute gout.
First response to treat MSU crystals?
Joint rest, application of cold packs, anti-inflammatory drugs, colchicine (inhibits PMN microtubular function and migration but only at toxic concentrations=very weak anti-inflammatory agent)
For patients with frequent attacks, tophi at young age, and renal stones of any type, family history of gout, extreme hyperuricemia, how should you treat?
Uricosuric agents (probenecid)=for patients with normal urinary urate excretion. This blocks renal tubular resorption of uric acid and increases excretion.
For patients with renal stones or urinary urate excretion rates, uricosurics should be avoided (nephrolithaisis).
Allopurinol can be used to block purine degradation. Allopurinol gives feedback inhibition at initial rate-limiting step of synthesis governed by enzyme PRPP-aminotransferase.
What is pseudogout?
Acute arthritis caused by CPPD crystal induced inflammation.
What age and gender?
Both sexes (pretty even)
Attacks occurring before age 50 are uncommon.
What are associated conditions of pseudogout?
Hyperparathyroidism, hypothyroidism, hemochromatosis, ochronosis, and even gout.
What do CPPD crystals look like under polarizing light microscopy?
Smaller size, typical intraphagolysosomal location, lower population, less brilliant colors.
Weak positive birefringency and squared ends.
**Calcium pyrophosphate crystals may exist in joint fluid asympatomatically.
What is pathophysiology of pseudogout?
Alteration in integrity of joint cartilage: Crystalline formation follows because of poorly defined interactions with constituents of altered cartilaginous matrix.
Deposits in articular cartilage, and cartilage of tendons/ligaments.
