Gout Pathophys

Question 1

Define Gout. Why is is called “disease of kings”

Answer 1

Inflammatory arthritis caused by an accumulation of EXCESS urate crystals (monosodium urate crystals) in joint fluid

disease of kings due to its association of rich foods & alcohol consumption

Question 2

What are the 2 types of presentation of gout?

Answer 2

Hyperuricemia
1. Increase production of serum uric acid OR Decrease elimination of serum uric acid
2. Tophaceous gout: more severe and chronic + tophi presence

Can be a combination of both

Question 3

What does an increase in serum uric acid result in?

Answer 3

Deposition of monosodium crystals in synovial fluid of joints

Question 4

What is uric acid a by-product of?

Answer 4

By-product of purine metabolism (biggest risk factor)

Question 5

Is hyperuricemia a prerequisite for gout?

Answer 5

No, some patients can have gout and normal SUA levels

Question 6

What are normal SUA levels? What about if associated with tophi or severe gout?

Answer 6

Normal: <360 umol/L

With tophi or sever gout: <300 umol/L

Question 7

What are some causes of OVER production of Uric acid? what abut UNDER-excretion?

Answer 7

Over production <10%
- too much alcohol
- too much rich foods

Under-excretion 90%+
- renal impairment
- hypertension
- Meds

Question 8

How to diagnose gout?

Answer 8

Using polarized light microscopy
- Yellow, needle-like crystals are daignostic for gout

Question 9

Explain why renal impairment is a risk factor for gout?

Answer 9

Main cause of under excretion of uric acid

Renal impairment (= decreased GFR) causes secretion/reabsorption of urate to fail resulting high serum concentration of uric acid

• gout can indicate early kidney disease

Question 10

Why is hypertension a risk factor for gout?

Answer 10

serum urate levels may be a partial intermediate on the pathway between HTN and gout

• meds used to treat HTN (diuretics) can also precipitate a gout attack

Question 11

Explain the relation of DM and gout

Answer 11

They are both linked together
- insulin resistance may play a role in development of gout/hyperucricemia

Question 12

Why is obesity a risk factor of gout?

Answer 12

Extra weight slows down the kidneys ability to remove uric acid

Question 13

Explain the effect of beta blocks and Alpha 1 blockers on gout

Answer 13

Decrease GFR –> increase SUA levels

Question 14

Explain the effect of diuretics on gout

Answer 14

increase urination = risk of dehydration
- remaining serum more concentrated with uric acid

• decrease in GFR and decrease in excretion rate
• increase uric acid reabsorption in proximal tubules

Question 15

Explain the effect cyclosporine on gout

Answer 15

decreases GFR, increases uric acid reabsorption in proximal tubules

Question 16

Explain the effect aspirin on gout

Answer 16

increase uric acid reabsorption + decrease uric acid secretion

Question 17

Explain gout at a cellular level after the deposition of MSU crystals

Answer 17

1. Activate leukocytes and induce inflammatory response (gout attack)
2. Inflammatory cells produce chemokines –> DESTROY cartilage and bone
3. Deposits can extend out from a joint and destroy ligaments –> lead to subcutaneous MSU deposits –> erode through skin (TOPHI)

Question 18

Why does the severe pain of gout occur overnight?

Answer 18

Lower body temperature at night –> increase urate crystal formation

Question 19

Where is the first place to get gout? Why?

Answer 19

In big toe (PODAGRA)

• uric acid at cooler temperatures turns into crystals
• big toe is the farthest from the heart so it is the coolest part of the body

Question 20

What is the gold standard for diagnosis of gout

Answer 20

Joint fluid aspirations

Question 21

Explain asymptomatic hyperuricemia

Answer 21

High uric acid levels, no symptoms of gout
- no therapy required if there is no symptoms
- recommend some non-pharms

360+ umol/L in females
420+ umol/L in males

Question 22

Explain acute gout attack (gouty arthritis)? how long does it take to subside

Answer 22

Urate crystals have been deposited cause gout flare
- subsides in 3-10 days
- triggered by: stress, alcohol, drugs

Question 23

Explain intercritical gout

Answer 23

Asymptomatic period in between attacks of gout
- more urate crystals being deposited
- recurrent attack 6-24 months

Question 24

Explain pseudogout

Answer 24

Mainly in the knee
- Irritated by calcium pyrophosphate dehydrate crystals (CPPD)

Question 25

Explain chronic tophaceous gout

Answer 25

happens 12 years after first gout attack

Tophi: hard uric acid crystal deposits under the skin
- painless –> lead to permanent damage of the joints
- in patients receiving inadequate treatment for gout
- can dissolve overtime if treated