HYHO: Gout and Pseudogout Flashcards
Purines
PUR-DOUBLE-AG
- Adenine
- Guanine
Pyrimidine
- Cytosine (DNA)
- Thymine (DNA)
- Uracil (RNA)
How is uric acid formed in the body?
Degradation of purines (A,G) => produces uric acid.
Degradation pathway that forms uric acid
Inosine => hypoxanthine => xanthine => uric acid
What enzyme catalyzes the final 2 reactions in the formation of uric acid?
Xanthine oxidase
- Hypoxanthine => Xanthine via XO
- Xanthine => uric acid via XO.
Humans source of purines
- Diet
2. Nucleotide synthesis and breakdown
How do we excrete/get rid of uric acid?
- Kidneys (70%) via pee
2. Gut (30%) via poop
Too much uric acid can form what
MSU crystals
What is gout?
Intermittent painful, inflammatory joint attacks, in response to uric acid crystals due to hyperuricemia
RF for gout
- Males
- Older ppl
- Pacific islander
- HTN/hyperlipidemia/CV disease
- CKD
- Meds: Thiazides
- Diet (alcohol and red meat)
- Lead
Why is gout MC in men than women?
Estrogen increases the excretion of uric acid, making it less common in premenopausal W.
What meds increase risk of gout?
Thiazides
What foods/drinks increase risk of diet?
Alcohol and red meat
_______ = uric acid deposition in tissue
Gouty tophi
Hyperuricemia is due to what?
- Overproduction (hepatic metabolism and cell turnover)
2. Underexcretion (from mostly kidneys)
What is the main cause of hyperuricemia?
Underexcretion
Clinical presentation of gout
- Acute onset joint pain, most painful in 1st 24 hours that often begin at night.
- Joint = swollen, painful red and warm
Gout is MC in what joints?
- 1st MTP (podegra)
- Knee
- Ankle
Provoking factors for gout flare
- Alcohol
- Trauma
- Inflammatory states (infection, surgery, MI)
- Dehydration
Definitive diagnosis of gout
Arthrocentesis of joint’s synovial fluid
Send sample for: cell count, culture, and gram stain
_________ is used to look for monosodium urate crystals, which are
needle shaped, _____ birefringent crystals
Polarized light microscopy
negatively birefringent crystals
Other labs to diagnose gout
- Serum uric acid level
2. CBC with differential (to R/O septic arthritis: has L shit)
When are XR useful for patients with gout?
In chronic gout, to look for bony erosions (punched out lesions or overhanging edge)
NOT useful for acute flares
MSU crystals they appear ____ when parallel to the axis of the polarized field and ____ when perpendicular to the axis
Yellow = parallel
Blue = perpendicular
Calcium pyrophosphate crystals are rhomboid, pale, and weakly (not as vividly) ______ birefringent; they appear _____ when parallel to the axis and _____ when perpendicular.
Weakly positively birefringent
Blue = parallel
Yellow = perpendicular
Non-inflammatory arthritis has synovial fluid with ______ WBCs/μL
-Typically d/t?
< 2,000
Mechanical or degenerative disorder (Osteoarthritis)
Inflammatory arthritis has synovial fluid with ______ WBCs/μL
-Typically d/t?
> 2,000
AI (RA, spondylarthritis, ankylosing, psoriatic arthritis), infection or crystal-induced
Infectious (septic) arthritis has synovial fluid typically with ________ WBCs/μL
What helps differentiate this etiology from others?
> 20,000 - 50,000
Gram stain and fluid culture
Crystal-induced fluid can vary but typically has between ________ WBCs/μL
Typically d/t?
10,000-50,000
Gout or pseudogout
Treatment of
Acute Gouty Flare
- Untreated gout will resolve within days to weeks (but it will be a very painful period)
1. NSAIDS (Indomethacin, Naproxen, etc…)
- Colchicine (inhibits cytoskeletal function of neutrophils preventing activation and
migration of neutrophils) - Glucocorticoids (oral Prednisone or intra-articular/IM steroid injection)
- May be preferred treatment option in patients with CKD
When treating patients with gout and chronic kidney disease (CKD), what medications should you avoid? What should you use instead?
Avoid = NSAIDS and colchicine
Instead, use oral steroids or intra-articular steroids.
Treatment of
Chronic Gout
- XO inhibitors (Allopurinol or Febuxostat)
- Uricosuric agents (Probenecid and Lesinurad)
- Uricase (Pegloticase)
What medication should you NOT give during a acute flare of gout, because it cause another one?
XO inhibitors (Allopurinol and Febuxostat): wait 2 weeks after flare
MOA of uricase drugs (Pegloticase)
Humans lack uricase which converts uric acid into highly soluble allantoin.
PEARL: What drug used to treat HTN also has uricosuric effects?
Losartan
If patient has SEVERE gout and if all other treatments have failed, what is the last resort?
Pegloticase
Goal serum uric acid level:
< 6.0 mg/dL in patients without tophi
< 5.0 mg/dL in patients with tophi
Prevent gout measures
Avoid of factors that cause hyperuricemia:
- Red meat
- Seafood
- Alcohol
- High-fructose corn syrup beverages
What is pseudogout?
Deposition of calcium pyrophosphate (CPP) crystals in and on cartilaginous surfaces that can
provoke an acute inflammatory arthritis, similar to gout
RF for pseudogout
- Age > 60
- OA
- Metabolic diseases:
(Hyperparathyroidism, hemochromatosis, hypophosphatasia (rare genetic disease), hypomagnesemia)
Pseudogout clinical presentation
- Asymptomatic to symptomatic
- Monoarticular or oligoarticular arthritis
- Joint is typically swollen, erythematous, warm, and painful
- fever can also be seen
Pseudogout MC affects what joints?
- Knee
- Wrist
- Rarely the 1st MTP joint
How is pseudogout different from acute gouty flare in how long it lasts?
Acute attacks of CPPD
disease = weeks to months
Regular gout = days - 1 week
-Provoking factors for Pseudogout flares
- Surgery
2. Acute illness
Definitive diagnosis of pseudogout
Arthrocentesis of synovial fluid
-Polarized light microscopy is used to look for CPP crystals,
Can XR be used to dx pseudogout?
No, but can support it by finding chondrocalcinosis (cartilage calcification, but not specific)
Treatment of pseudogout
- NSAIDS
- Colchicine
- Intra-articular glucocorticoid injection or oral prednisone
- Treat underlying metabolic disease if present
ANS innervation to kidney
Sympathetics: T10-11
Parasympathetic: Vagus N (OA,AA)
ANS innervation to UE and LE
UE: T2-7
LE: T11-L2
Respiratory/circulatory for gout
lymphatic OMT
Neurologic for gout
OMT to NL sympathetics and parasympathetics
Metabolic/NRGTIC/immune for gout patient
- Do Arthrocentesis for acute gout flare to confirm dx.
- Assess uric acid levels
- Assess renal function and renal dose medications as needed (i.e. NSAIDs,
Colchicine, and allopurinol) - Caution with systemic steroid use in diabetics (may need to check glucose more
frequently or give insulin temporarily) - Consider stopping Thiazide if recurrent gout (Thiazides raise uric acid levels)
Caution with systemic steroid use in who? and why?
Diabetics: may need to check glucose more often or give insulin temporarily
Behavioral for gout patient
Avoid red meats, seafood and alcohol
