Gout

Question 1

What is uric acid

Answer 1

The waste product of purine metabolism

Question 2

What are purines

Answer 2

metabolic acids discovered in the nuclei of cells
DNA nucleic acids–> genetic material (genes), control protein synthesis
RNA nuclei acids–> relay instructions from genes to cells regarding synthesis of amino acids to protein
Hence uric acid is the end product of purine metabolism from DNA and RNA metabolism

Question 3

Purine production

Answer 3

only good in moderation

over production or decreased salvage/excretion causes increased uric acid levels

Question 4

What is the salvaged pathway of purine production

Answer 4

Purine bases are recaptured from the breakdown of nucleic acids from endogenous sources and dietary sources

Question 5

What is the new pathway of purine production

Answer 5

Synthesised from non-purine precursors

Question 6

What is gout

Answer 6

Metabolic disorder/imbalance
Incomplete purine metabolism–> disruption in the body’s control of uric acid and small serum uric acid levels
Over production or under secretion of uric acid
saturated levels of uric acid in soft tissue therefore forms crystals in joint connective tissue and within joint space
Recurrent pain and joint inflammation (chronic infammation)

Question 7

What is hyperuricemia

Answer 7

high uric acid in blood (>7mg/dl is considered elevated

Question 8

What is the cause of primary gout

Answer 8

Hyperuricemia–> unknown cause of hyperuricemia
Inborn error in metabolism
Mainly men (40-60yrs)

Question 9

What is the secondary cause of gout

Answer 9

Chronic renal/kidney failure–> hence decreased ability to excrete uric acid/purines= increased uric acid levels
Leukaemia (blood cancer)/lymphomas treatment–> increased acid turnover
Known genetic abnormalities
Some diuretics interfere with uric acid excretion

Question 10

Predisposers of hyperuricemia

Answer 10

Genetic predisposition
Age--> older than 30
heavy alcohol consumption
obesity
certain medications (asprin)
lead toxicity

Question 11

What type of crystals from in pseudogout

Answer 11

Calcium pyrophosphate crystals

crystal deposition in joint

Question 12

Incidence of pseudogout

Answer 12

30-80% by 85yrs

Male and female at equal risk

Question 13

What type of disease is pseudogout

Answer 13

sporadic/idiopathic

Question 14

Hereditary risk factors of pseudogout

Answer 14

ANKH gene
crystals develop early in life
associated with OA

Question 15

Secondary risk factors of pseudogout

Answer 15

Previous joint damage
Hyperparathyroidism
Diabetes

Question 16

What type of crystals form in gout

Answer 16

Monosodium urate crystals

Uric acid crystals deposition in joint

Question 17

What are the manifestations of gout

Answer 17

Increase in serum urate concentration (hyperuricemia)
Recurrent attacks of monoarticular arthritis (inflammation of a single joint)
Depositions of monosodium urate monohydrate (TOPHI) in and around joints
Renal disease involving glomerular, tubular and interstitial tissue and blood vessels
Formation of renal stones

Question 18

What is the first stage of gout progression

Answer 18

Asymptoatic hyperuricemia
High levels of serum urate without symptoms or arthritic
Usually around puberty in males and menopause in females
This stage may persist throughout life

Question 19

What is the 2nd stage of gout progression

Answer 19

Acute gouty arthritis
Attacks of sings and symptoms of gout with increased serum urate concentrations
Tends to occur with sudden or sustained increases of hyperuricemia (can also be triggered by trauma, durgs and alcohol)
Sudden onset of pain
Monoarticular–> usually 1st MTPJ

Question 20

What is the 3rd stage of gout progression

Answer 20

Asymptomatic intercritical
Dependent on predisposers control
May get second attack
May become polyarticular

Question 21

What is the 4th stage of gout progression

Answer 21

Chronic tophaceous gout
Causes kidney/eye damage (macular degeneration)
Chronic stage of disease
Progressive inability to secrete uric acid expands the urate pool untill monosodium urate crystals appear in cartilage, synovial membrane, tendons and soft tissues
Start getting crunchy in joints due to crystal formation
Also become swollen, hard and inflammation continues

Question 22

What is topus and tophi

Answer 22

Topus= Porous stone, soft yet gritty
Tophi= large aggregate of urate crystals and surrounding inflammatory process

Question 23

Why do urate crystals form and collect in joints

Answer 23

Synovial fluid is not a good solvent as plasma, hence crystals last longer in joints
Crystals are also less soluble at lower temps z(<37); big toe is very peripheral hence lower temp and t/f prime site

Question 24

How do urate crystals cause an inflammatory response

Answer 24

Urate crystals interact wit local macrophages (inflammation) and dendritic cells (immune system)
Phagocytose of crystals release lysosomal enzymes
Causes destruction of cartilage and subchondral bone
Inflammatory process well under way

Question 25

How does remission of acute gout episodes occur

Answer 25

production of anti-inflammatory cytokines Recoating of uric acids Removal of damaged neutrophils

Question 26

What is the treatment of acute gout episodes

Answer 26

Aim to avoid recurrent episodes and prevent complication in joints and kidneys (formation of kidney stones) diet--> increase veges and decrease meats High water intake Avoid WB Ice on Joint (decreases swelling and hence pain) Anit-inflam meds--> prevents joint infections and decrease pain Need to control and prevent renal involvement