Term
| What are the major crystalline arthropathies in humans and how do you differentiate between them? |
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Definition
SHORT
Gout= hypertension/obesity with uric acid in 1st MTP and forefoot/ankle of men
CPPD= hemocromatosis, osteroarthritis with calcium pyrophosphate in wrists and knees of men and women
The fatties with hypertension have gout!
1) Gout- overproduction/under-secretion of uric acid and associated with hypertension and obesity. Presents in 1st MTP and forefoot/ankle
2) Pseudogout- deposition of calcium pyrophosphate (CPPD) and is associated with osteoarthritis, hemochromatosis, hyperparathyroidism, hypophosphatemia, osteodystophy. Presents knees and wrists. |
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Term
| How do you differentiate acute gout from psuedogout? |
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Definition
Acute gout presents with Men (some post-menapausal women), with yellow, negatively birefringent, parallel crystals (yellow, parallel, allopurinol)- usually in the 1st MTP. These crystals often penetrate PMNs.
CPPD crystals are rhomboid shaped and positively birefringent, usually found in older men/women. |
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Term
| How do you differentiate gout from psuedogout? |
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Definition
Gout-
Location (1st MTP and forefoot)
Birefringence (negative)
Elevated Uric acid, tophi, renal calculi and olecranon
bursitis
Pseudo-gout
Location (Wrists and knees)
Birefringence (positive)
On x-ray, white fluffy radioopaque deposits b/w joints
Both men and women |
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Term
| What are some important epidemiological facts regarding gout |
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Definition
1) most common form of inflammatory arthritis in men (1-2% of men) (RA is most common in women)
2) Prevalence doubled since 1969 (longevity, hypertension, diet, diuretics, calcineurin inhibitors for transplant)
3) Elderly men and postmenopausal women
4) Higher uric acid associated with high risk
5) Associated with increased risk of CAD, MI, CVD |
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Term
| What is associated with hyperuricemia? |
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Definition
1) CAD
2) CAD-related death
3) Risk for mortality in systolic HF |
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Term
| What is the pathophysiology of gout? |
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Definition
1) too much urate (>6.8mg/dl) forms crystals in joints, kidneys and skin (tophi)
2) Humans lack uricase enzyme, which degrades uric acid to allantoin (high serum uric acid leads to high BP)
3) Uric acid can act as a "danger signal" and acts as an antioxidant
4) Purine breakdown produces Uric acid via Xanthine oxidase (allopurinol and febuxostat treat gout) |
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Term
| How do Allopurinol and Febuxostat treat Gout |
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Definition
Both are used to treat chronic gout.
Allopurinol inhibits Xanthine oxidase to prevent hypoxanthine-xanthine transition.
Febuxostat inhibits Xanthine oxidase to prevent xanthine-uric acid transition. |
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Term
| Why might you give pegloticase (pig) or rasburicase? |
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Definition
These are forms of uricase which would increase uric acid breakdown to Allantoin. Treat the gout!
The peglotinine is a polysacharide that increases the half-life of the uricase enzyme for the treatment of hyperuricemia. |
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Term
| What is the distribution of "under-secretors" to "over-producers"? |
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Definition
1) 85-90% are under-excretors (renal defects).
Excretion may be normal in absolute terms, but is low in relation to serum uric acid.
2) 10-15% are over-producers (enzyme abnormalities)
Typically also over-excretor |
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Term
| Where does reabsorption and secretion of uric acid in the urine occur? |
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Definition
Renal proximal tubule.
Probenecid and Benzbromarone block re-uptake of uric acid by the URAT1 (urine-tubule) and SLC2A9 (blood-tubule and urine-tubule) urate transporters. |
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Term
| Why might you prescribe Probenecid and Benzbromarone to treat gout? |
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Definition
They block re-uptake of uric acid by the URAT1 and SLC2A9 urate transporters in the proximal tubule.
Pee it out! |
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Term
| Why might you give Colchicine and IL-1 inhibitors to people suffering form gout? |
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Definition
1) Colchicine blocks microtuble stimulation by uric acid crystals in inflammasomes of myeloid cells, and prevents NALP3 activation (important for caspase-1-mediated cleavage of pro-IL-1b.
2) IL-1 inhibition would prevent inflammation associated with gout. |
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Term
| What does IL-1 produced in the joint do? |
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Definition
1) Induces cyclooxygenase and prostaglandin release
2) activates HSP
3) Stimulates TNF
4) Stimulates hepatocytes to secrete CRP
5) increase blood neutrophil
6) fever |
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Term
| What treatments are available for the gout? |
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Definition
1) Treatment of acute and 2) Therapy for chronic treatment or prevention of gout.
1) NSAIDS, corticosteroids, colchicine, IL-1 antagonist
** use NSAIDs and colchicine with care in patients with hepatic insufficiency or renal insufficiency **
2) Uricosurics (probenecid/benzbromarone)- not good with renal insufficiency
Xanthine oxidase inhibitors (allopurinol and febuxostat)
Cochicine (for gout flares, but not to lower uric acid)
Pegloticase |
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Term
| What treatments are available for acute treatment pseudo-gout? |
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Definition
1) NSAIDS
2) Corticosteroids
3) Cochicine for pseudogout flares |
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Term
| What treatments are available for chronic pseudo-gout? |
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Definition
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Term
A 65 year old patient presents with painful swelling of his 1st MTP and of the dorsum of his foot with extension of his ankle. He has no history of such attacks.
What is his condition and what other symptoms/clinical features might you predict?
How would you treat? |
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Definition
Acute gout.
The fact that he is a man and the location of the swelling are strong cues.
You might also expect elevated Uric Acid (>6-7), yellow/negatively bifringent needled-shaped crystals
Since this is an acute case, treat with steroids, NSAIDS, Colchicine and IL-antagnosts. If they have nephrotoxicity, don't treat with Colchicine or NSAIDS. |
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Term
A 54 year old woman with a history of polyarthritis presents with chondrocalcinosis in her peripheral and axial joints, with features of OA in the writs and knees.
What is your diagnosis? What other clinical features might you expect to see? How would you treat? |
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Definition
Psuedogout
The fact that she is a woman, the location of the OA and the chondrocalcinosis are suggestive.
You would also see calcium pyrophosphate crytals that are rhomboid shaped and possess a positively birefringent character.
CPPD often occurs in the context of Hemocromatosis and OA, and is associated with fluffy white radioopaque deposits on X-ray. |
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Term
True or False.
You should treat a patient who is experiencing hyperuricemia to prevent the onset of gout. |
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Definition
False!
Don't treat them immediately; wait to see if you are right first. |
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Term
| What is an evolutionary explanation for why humans and higher primates lack the uricase enzyme? |
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Definition
Uric acid levels can increase BP, which could be important in low-salt climates.
Also, Uric acid may act as a danger signal in the innate immune system, binding TLR2/4 |
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Term
| What happens if you knock out uricase in mice? |
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Definition
NO GOUT
They get kidney failure from uric acid crystal deposits. |
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Term
| How can you treat hyperuricemia? |
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Definition
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Term
| How can you treat hyperuricemia? |
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Definition
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Term
| How can you treat hyperuricemia? |
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Definition
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Term
| How can you treat hyperuricemia? |
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Definition
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Term
| What happens FIRST when you treat gout Allopurinol? |
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Definition
| You will most likely see a gout flare (so give with steroids), because the big crystal is being broken up into smaller crystals. |
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