Gout is defined as deposition of ____ due to prolonged _____?
monosodium urate (MSU), hyperuricemia
hyperuricemia can result via what 2 ways? Think broadly
Overproduction, decreased efficiency of excretion
His fact: Excretion of uric acid (as in the # of mg you collect over 24 hours is normal). so its clearance that is decreased
requires a higher plasma level of uric acid such that production and clearance can be equal
What is the difference between monosodium urate and uric acid?
Uric acid is what is excreted in urine, monosodium urate (MSU) is what accumulates. So gout is an accumulation of MSU, not uric acid.
Hyperuricemia defines as plasma urate level greater than?
What type of patient almost never gets gout? Why?
Premenopausal females, estrogen is thought to increase the excretion of uric acid. #feminism
Early manifestations/location of gout? Name given to this? Time length of involvement?
begins as a acute monoarticular arthritis of lower extremity joint. If it involves 1st MTP = podagra. Symptoms will usually resolves in 5-7 days
What factors (list 3) lead to early manifestations of gout? i.e. why the big toe
Lower extremity has:
- decreased blood supply
- decreased pH at night (increased acidosis)
- decreased temperature at night.
These factors all lead to precipation of urate, forming crystals. Often patient wakes up in the morning in pain
Chronic gout can cause urate crystals to accumulate in large deposits within joints. What are these deposits called?
Tophi. Path slides later in flashcards
In later stages, gout can resemble what other joint disorder? List common features? List differentiating feature?
Can resemble RA
Common features: polyarticular involvement
Joint involvement in gout is asymmetrical, RA is symmetrical
Is primary or secondary gout more common?
In primary hyperuricemia, which has a greater impact on gout, decreased efficiency of excretion or increased production of uric acid?
Decreased effiency of uric acid excretion - 90%
Increased production of uric acid - 10%
Secondary hyperuricemia and gout are usually related to what?
decreased renal urate clearance as a direct or indirect consequence of the primary disease process (meaning a disease is causing the gout)
What accounts for less than 1% of secondary hyperuricemia and gout?
Four known specific inborn errors of purine metabolism with overproduction of urate
Under excretion of uric acid is a misnomer. Why? Describe what they mean by this.
"under-excretors" actually still excrete the same amount of uric acid. They just require a higher serum concentration of uric acid to excrete this amount. This increased serum concentration is what causes gout
Males or females have higher urate concentrations normally?
Males, 2x the amount of females
Intestinal metabolism of uric acid accounts for what % of total urate metabolism?
Xanthine oxidase is involved in what step(s) of uric acid formation?
Hypoxanthine→ Xanthine → Uric acid
Urate in kidney
What % of originally filtered urate wounds up being excreted?
8-12% of filtered is actually excreted
Urate freely filtered (100%) then 98-100% reabsorbed in PT. Again 50% secreted back into PT and largely reabsorbed. Back and forth game, lots of transporters we probably dont need to know.
In men, primary hyperuricemia begins when?
What reduces the risk of developing gout in pre menopausal women?
Estrogen, increases urate clearance
Men or women experience highest incidence of gout b/t 30-45 years of age? At what age does the other sex usually get it?
What cells play a huge role in gout? How?
- urate crystals deposit in joint, trigger acute inflammatory reaction (neutrophil influx and chemotaxis)
Besides joints, what other parts of body can be affected by gout?
helix of ear, achilles tendon
Does gout cause destruction of the joint?
What radiographic finding of a joint is pathognomonic for gout?
Kid bites his own lips and self mutilates himself? What disease? What genetic mutation?
Lesch-Nyhan Syndrome; X-linked deficiency of HGPRT (hypoxanthine-guanine phosphoribosyltransferase...try saying that 3 times)
What diuretics promote hyperuricemia?
Loop, Thiazide diuretics
What drug did Dr. P do research on that causes hyperuricemia? List other drugs that can cause it
Loop and thiazide diuretics, pyrazinamide, Salicylates (low dose), Nicotinic acid, Cyclosporine, Ethanol
Uric acid stones account for what % of urinary tract stones?
3 major risk factors for uric acid nephrolithiasis?
increased uric acid excretion, reduced urine volume, low urine pH
What do you want to do to urine to decrease risk for uric stones?
alkalinize the urine
What clnical conditions are commonly associated with hyperuricemia and gout?
HTN, CAD, Dabeetus, obesity, alcoholism, renal insuffiency, lead poisoning, hypothyroidism
What foods increase risk for gout?
alcohol consumption (beer), seafood (shrimp,lobster) red meat
red wine may actually be protective
Moonshine can cause what that leads to gout? How?
lead poisoning (produces interstitial nephritis, which interferes with uric acide excretion)
Gross description of tophi?
White chalky aggregates of uric acid crystals
Microscopic description of tophi?
fibrosis and giant cell formation
Gout under polarized light (3 features)
Negative birefringence, needle shaped, yellow under parallel
What slide fixation ruins microscopy of gout? What is best method to view it?
Formalin fixation dissolves urate deposits
Alcohol fixation with silver stain is best (shown in picture, dark stained stuff is urate crystals)
This is an image of what?
Urate deposits in kidney, almost look like stellate stars
Other disease that involves crystal deposition?
Calcium pyrophosphate Dihydrate (CPPD) Crystal Deposition Disease
List some metabolic abnormalities associated with CPPD?
Biggest factor for CPPD?
Age, average age is 70-75
CPPD sex preference?
M = F
Most common form of CPPD?
Asymptomatic form, not pseudogout
Recurrent acute inflammatory monoarticular arthritis associated with CPPD is called what?
Injection of what into joint space can actually worsen pseudogout?
Intra-articular hyaluronan (used to treat other joint disorders)
RA and CPPD common radiographic findings? Differentiating findings?
Similar: Subchondral sclerosis, joint space narrowing
Different: No erosions (erosions present in RA)
Familial CPPD disease is linked with what gene?
ANKH gene on chromosome 5p
Main way to tell CPPD from OA?
Location of joint involvement. CPPD will involve MCP joints, wrist, elbows, glenohumeral joints)
If patient has CPPD under the age of 55, what disorder should also be considered?
What disease is associated with accumulations of hydroxyapatite?
Calcium Hydroxyapatite (HA) Deposition Disease
Hyperphosphatemia in HA deposition disease is usually associated with what other condition?
Chronic renal failure, hyperphosphatemia enhances HA deposition both in and around joints.
- CPPD deposition disease can be seen in these patients too
Unlike urate and CPPD crystal deposition, what is NOT seen in HA deposition disease?
Acute synovitis is unusual
CPPD under polarized light (3 features)?
positively birefringent, rhomboid shaped, blue under parallel light
What are these? What disease can they be seen in?
Cholesterol crystals, may be seen in RA