Pathophys - Gout Flashcards by amanda kastel

what is the immediate cause of gout

persistent elevated levels of uric acid in the blood

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name 3 underlying causes of gout

mainly genetics

diet

other comorbidities

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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)

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true or false

psoriasis is a comorbidity that can increase the risk of developing gout

true

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gout is a form of _______ arthritis in the ______

inflammatory arthritis in the joints

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uric acid is a byproduct of what?

purine metabolism

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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)

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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

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gout is characterized by recurrent attacks of what?

of red, tender, swollen, and painful joints

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gout may also affect…….

the kidneys!

can form kidney stones and lead to tubule damage

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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

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is gout genetic?

yes, genetics can play a role but so can many other factors (like diet)

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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

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name 6 purine-rich foods

meats
seafood
alcohol
mushrooms
beer yeast
seaweed

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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

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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