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Flashcards in Gout Facts Deck (27):
1

Lifestyle factors that contribute to gout? 

Obseity

diet of meat and seafood

EtOH - binds to same receptors in kidney for excretion!!!! leads to build up

 

high fructose corn syrup

2

DRUGS THAT LEAD TO GOUT

Thiazides

ASA

Cyclosporine

Nicotininc ACid

LevoDopa

 

 

That Ass Cycles Not-Anything Like-Dope

3

Describe metabolic pathway of gout

Purines A and G broken down into Hypoxanthine and then need Xanthine Oxidase to make Xanthine and then again to make Urate which is a waste product and excreted by kidney

4

How is Uric Acid handled in the kidney? 

Uric Acid Transporter - URAT 1 on Luminal side of Proximal tubular epithelial cell - into peee pee 

 

OAT 1 and 3 on Interstitial side (BSL) of PRoximal tubule - into blood 

5

Hyperurecemia/Supersaturation of Uric Acid leads to __________ crystal formation and deposition in the tissues. What happens from there to cause gout attack? 

Monosodium Urate Crystals deposit in tissues

 

Then opsonized by IgG and complement and/or just plain old phagocytosis by a MOnocyte and ROS generated inside to activate Inflammasome and relase of IL1beta and  leads to release of Cytokines like IL1, IL6, TNF alpha etc for PRo-Inflammatory cascade that recruit PMNs and other shit to come and start craziness

 

I

6

What cytokine accounts for systemic features of gout? What changes does this cytokine cause? 

IL1Beta 

Recruits PMNs

ROS from phagocytosis of crystals in monocytes activates TLR 2 and 4 to make NALP3 inflammasome and release ILbeta which recruits PMNs and wreaks havoc 

 

7

List the 4 stages of gout

Asymptomatic Hyperuricemia

Acute Intermittent Gout

Inter-critical Gout

Advanced Gout

8

Stage 1 - Asymptomatic Hyperuricemia - what do you do? 

No treatment and NOT gout. no signs or symptoms 

only 30% hyperuricemia leads to gout

 

 

Make lifestyle modifications like weight loss, less ETOH, change diet, increase Vitamin C etc

9

What is the presentation of an Acute Gout attack? what about an atypical attack? 

Acute inflammation and RAPID development of intense pain, swelling tenderness and redness - at nigth and in early morning bc lower body temperatures for precipitation at night

 

 

MONOARTICULAR - often Podagra (big toe!) 

 

In advanced disease, attacks can be polyarticular or atypical like Olecranon Bursa or achilles

10

What's happening/presentation in Inter-critical Gout stages between flares? 

Urate crystals can be found even in asymptomatic joints 

 

Chronic  low greade inflammation can occur from crystals

Development of tophi 

11

Advanced Gout - What do you see? 

Persistent, DESTRUCTIVE arthririts

(after 10 years or so) 

 

Tophaceious deposits

RAT BITES in bones bc degradation 

Can be confused w/ RA 

Drain Topus and see chalky white fluid - ewwww that's fucking nasty

12

Different Ways to Dx gout? 

id MSU crystals in synovial fluid or tissue is the best

use polarized light microscopy and yellow when in parralel and blue perpendicular

"Negativel Befringent" 

Rat Bite on Radiograph 

Synovial fluid can be inflammatoyr so RULE OUT INFECTION - ALWAYS GRAM STAIN bc can coexist 

13

People w/ transplants get gout - why? What' sthe presentation of this gout? 

Cyclosporine induced Gout!!!! 

 

complicated by calcluli and tophi

Hyperuricemia, renal insufficiency 

Cyclosporine induced Tubular defect in urate secretion 

14

What Chemical element ca ncause gout? Exposures? 

Saturnine gout from Lead poisoning bc inhibits excretion of urate 

 

Moonshine!!1

Painters, plumbers, pipers, battery or steel workers etc 

15

Goal of Gout treatment? Acute management vs chronic? 

GOAL - always want serum uric acid < 6 (6.8) to prevent flares and tophus formation 

 

Acute Rx: NSAIDS, steroids, Oral Colchicine, IL1 inhib

Chronic Rx: Colchicine, Allopurinol, Febuxostat, Probenacid (NOT in renal pts) 

16

NSAIDS to use in gout? 

Indothemacin 

 

caution in elderly and those w/ renal impairment

17

What the heck is Colchicine? Adverse effects?

Most effective when used in 12-24 hours of atack

Binds to Tubulin Dimers and prevents them from moving so stops chemotaxis, phagocytosis, etc 

 

Adverse Effects: Narrow therapueitc window

DIARRHEA and Myonecrosis 

18

What is the IL-1 tx used for acute attacks? how does it work? 

ANAKINRA - Kineret

IL-1 Receptor Antagonist give SQ shot for 3 days 

19

What's Allopurinol? How does it work? Adverse Effects?

Inhibits XO and metabolite Oxypurinol lowers serum Uric acid and dissolves tophi 

 

FX: DRESS syndrome hypersensitivity and Steven's Johnsons 

Toxic Epidermal Necrolysis 

BAD FOR KIDNEYS!!! 

 

CONTRAINDICATION w/ Azathioprine or 6 MP = Pancytopenia bc shared metabolism w/ XO 

20

What's Febuxostat? Uses? Adverse effects? 

Non-purine selective XO inhibitor that decreases serum Uric Acid and dissolves Tophi

 

good for those w/ Allopurinol allergy or Renal insufficiency bc metab through liver

 

FX: diarrhea, hepatic impairment, arthralgia

21

Probenacid? Effects? mechanism? 

Promotes renal uric acid excretion bc completely inhibits URAT1 exchanger on luminal side

 

FX: Drug interactions and increases concentrations of other drugs like Penicillin and Methotrexate

 

NOT GOOD for CrCl < 60 or pts w/ stones

22

We dont have Uricase. Only birds do. (lucky bastards). so like......what are we going to do about it? 

Uricase converts UA to Allantoin which is water soluble and we can get rid of Uric Acid 

 

TX: RASBURICASE or Pegylated Uricase  (Pegloticase) for refractory gout!!!

 

Caution: G6PD deficiency and CHF 

Anaphylaxis reaction 

 

23

What is Pseudogout? Causes? 

Calcium Pyrophosphate Dihydration Deposition disease - CPPD 

Calcium salt deposition in the cartilage causes painful arthritis 

*CHONDROCALCINOSIS 

from abnormality in Inorganic Pyrophosphate metabolism leads to progressive Osteoarthritis 

24

Pseudogout - presentation? Findings? Difference from Gout? 

XR shows Chondrocalcinosis - linear calcification o cartilage

Meniscus, TFC cartilage of wrist, symphysis pubis, glenoid rim, hip, annulus fibrosis

 

weak + BIREFRINGENT CRYSTALS - RHOMBOID SHAPE and yellow in perpendicular and blue in parallel 

25

Tx pseudogout? 

NSAIDS

Colchicine

STeroids 

26

Milwaukee shoulder syndrome buzzwords? 

Hydroxyapatite crystals 

Rotator Cuff Disruption - erosion of Hymeral Head 

FEMALES IN 50s w/ Erosion of humeral head 

 

DX arthrocentesis and Alizarin red stain

27

Calcium Oxalate Arthropathy? 

Knees, elbow, ankles, mono or poly acute arthritis

 

Flexor Tenosynovitisis

NO RESPONSE TO COLCHICINE OR NSAIDS

Ca Ox Crystals 

Peri-articular and soft tissue calcification