Lifestyle factors that contribute to gout?
diet of meat and seafood
EtOH - binds to same receptors in kidney for excretion!!!! leads to build up
high fructose corn syrup
DRUGS THAT LEAD TO GOUT
That Ass Cycles Not-Anything Like-Dope
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
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
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
What cytokine accounts for systemic features of gout? What changes does this cytokine cause?
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
List the 4 stages of gout
Acute Intermittent Gout
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
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
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
Advanced Gout - What do you see?
Persistent, DESTRUCTIVE arthririts
(after 10 years or so)
RAT BITES in bones bc degradation
Can be confused w/ RA
Drain Topus and see chalky white fluid - ewwww that's fucking nasty
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
Rat Bite on Radiograph
Synovial fluid can be inflammatoyr so RULE OUT INFECTION - ALWAYS GRAM STAIN bc can coexist
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
What Chemical element ca ncause gout? Exposures?
Saturnine gout from Lead poisoning bc inhibits excretion of urate
Painters, plumbers, pipers, battery or steel workers etc
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)
NSAIDS to use in gout?
caution in elderly and those w/ renal impairment
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
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
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
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
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
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
What is Pseudogout? Causes?
Calcium Pyrophosphate Dihydration Deposition disease - CPPD
Calcium salt deposition in the cartilage causes painful arthritis
from abnormality in Inorganic Pyrophosphate metabolism leads to progressive Osteoarthritis
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
Milwaukee shoulder syndrome buzzwords?
Rotator Cuff Disruption - erosion of Hymeral Head
FEMALES IN 50s w/ Erosion of humeral head
DX arthrocentesis and Alizarin red stain
Calcium Oxalate Arthropathy?
Knees, elbow, ankles, mono or poly acute arthritis
NO RESPONSE TO COLCHICINE OR NSAIDS
Ca Ox Crystals
Peri-articular and soft tissue calcification