Pathophys - Gout Flashcards
what is the immediate cause of gout
persistent elevated levels of uric acid in the blood
name 3 underlying causes of gout
mainly genetics
diet
other comorbidities
name some comorbidities that can increase the risk of developing gout
older male
metabolic syndrome
renal failure
psoriasis!
lead poisoning
hemolytic anemia
polycytemia (inc RBC in blood)
true or false
psoriasis is a comorbidity that can increase the risk of developing gout
true
gout is a form of _______ arthritis in the ______
inflammatory arthritis in the joints
uric acid is a byproduct of what?
purine metabolism
typically, which joint is affected by gout?
around 50% of the time it’s the joint base of the big toe
(any joint can be affected, but not typically)
true or false
uric acid is always in the blood
TRUE
just normally, it’s at concentrations close to or lower than the levels needed to cause precipitation crystals to form and deposit in the joints
gout is characterized by recurrent attacks of what?
of red, tender, swollen, and painful joints
gout may also affect…….
the kidneys!
can form kidney stones and lead to tubule damage
true or false
gout is not life threatening
true(ish)
the disease itself is not, but the precipitation of uric acid crystals within the nephron can lead to kidney damage, which can be fatal
is gout genetic?
yes, genetics can play a role but so can many other factors (like diet)
explain how diet is an underlying cause of gout
uric acid is a byproduct of purine metabolism
therefore, consuming a lot of purine-rich foods can increase chance of getting gout
name 6 purine-rich foods
meats
seafood
alcohol
mushrooms
beer yeast
seaweed
explain the pathophysiology of gout
uric acid cystallizes because the blood levels are too high. these crystals then deposit in the joints, tendons, and surrounding tissues
true or false
in some cases, the uric acid blood levels may be NORMAL, but there’s still uric acid deposits in joints
true
this is a strange scenario which is not well understood
name the 2 mechanism of action that account for high levels of uric acid (aside from eating too many purines)
underexcretion of uric acid by the kidney (90% of the time)
overproduction of uric acid (other 10%)
GOUT IS A DISORDER OF ____ METABOLISM
purine
the crystals of uric acid form as what?
monosodium urate
as mentioned, the crystals of uric acid form as monosodium urate.
these urates precipitate where?
in tissues
what are “tophi”
the term for monosodium urate crystals that precipitate in the soft tissues of the body
the tophi may be……..
EXPLAIN
walled off by a ring of proteins. blocks the interaction of the crystals from the cell
this ring of proteins prevents the inflammatory reaction from occurring! however, as the joints move, the ring of proteins may break and urate crystals leak out from the tophi — this triggers a local immune-mediated inflammatory reaction
why might urate crystals leak from the tophi?
because of physical stress - moving the joint arounf
what is the cause of urate crystals leaking from the tophi
involves what specific cells?
a local immune-mediated inflammatory reaction is triggered, involving MACROPHAGES
As mentioned, when urate crystals leak from the tophi, a local immune-mediated inflammatory response involving macrophages is triggered
explain this immune response in more detail
the NLRP3 inflammasome protein complex initiates inflammation. it’s at the heart of a cell death pathway called, pyrrotosis
NLRP3 recruits and activates caspase 1 (enzyme) which converts pro-IL1B to the ACTIVE FORM - IL1B
IL1B is a key protein involved in the inflammatory cascade
what is the name of the inflammasome that initiates inflammation in gout
NLRP3 inflammasome
caspase 1 is associated with….
cell death
what is at the heart of NLRP3 mechanism
pyroptosis - a cell death mechanism
as mentioned, tophi may form in gout cases.
what are they formed from?
when uric acid crystals get surrounded by cellular elements (often histocytes)
in gout, ____ ___ may form
subdermal nodules – can vary in size
when urate crystals leak from the tophi, what can it cause
joint damage, with bone erosion and cartilage damage
as mentioned, the leakage of urate crystals from the tophi can cause joint erosion and cartilage damage
what is the significance of this?
can lead to osteoarthritis!
explain how the morphology of tophi can affect if gout is chronic or not
as mentioned, the tophi are covered with histocytes. if uric acid levels are lowered at this point, it’s possible that the gout can be solved
however, if the process is not relieved, fibroblasts may surround the outside of the structure, making it more permanent – chronic gout
AS THE CELLULAR ELEMENTS MATURE, THE TOPHI, AND THUS GOUT, BECOME MORE PERMANENT
as mentioned gout is thought to be a genetic disorder. in part of ________ inheritance
POLYGENIC – multiple genes involved
3 specific genes have been associated with gout
true or false
chronic kidney disease can cause gout
TRUE
when the nephron fails to filter out uric acid, leads to a buildup of it in the body —– gout
explain how gout can cause chronic kidney disease AND can cause kidney failure
can cause chronic kidney disease if the crystals precipitate in the nephron, causing tubular damage and chronic kidney disorder (possibly failure)
also, if the uric acid preceipitates to form kidney stones, they can get stuck in the head of the ureter and BLOCK OUTFLOW from the kidney – shuts the kidney down – renal failure
true or false
gout can cause chronic kidney disease but chronic kidney disease cannot cause gout
FALSE
both are true
chronic kidney disease can cause gout by the nephron not filtering out uric acid, causing its levels to build in the blood
nephron failure leads to…….
chronic renal failure
