2. What is Gout?
 Gout is defined as a peripheral arthritis, resulting
from the deposition of MSU crystals at one or more
joints.
 Characterized by Hyperuricemia
 Known as:
o Rich man’s Disease / Disease of Kings
o Poor man’s Gout

3.  Uric acid  Product of purine catabolism
 Ionized forms of uric acid readily form salt.
 98% of Uric acid forms monosodium salts
 MSU crystals form in synovial fluid when solubility
limit are exceeded.
 These crystals provoke an inflammatory reaction.

5.  Classifications:
 Primary Gout – 90%
 Overproduction
 Under excretion
 Secondary Gout – 10%
 Progression
 Asymptomatic hyperuricemia
 Acute gouty arthritis
 Intercritical Gout
 Chronic / Tophaceous Gout

6. Research has shown that risk factors for development of
gout can be attributed to the increasing longevity, dietary
and lifestyle changes and a history of comorbidities.
There is an increased incidence of gout among:
•Males between the ages of 20 – 40.
•Men have higher serum urate levels.
•Post menopausal women
•Patients on diuretics.
•Such medication increase reabsorption of uric acid in
kidneys hence increasing the risk of developing gout.
•Patients with hypertension, diabetes, hyperlipidemia,
chronic kidney disease, or the metabolic syndrome.
•Studies show that more than 60% of patients with gout have
the metabolic syndrome.

7.  Diet :
 Beer drinking, High red meat and seafood consumption
increases risk.
 Purine-rich vegetable consumption does not notably
increase risk of hyperuricemia and development of
gout.
 Both incidence and Prevalence of Gout is increasing.
 For example, Data from US managed care reflected an
increase in gout prevalence from 2.9 cases per 1000
persons in 1990 to 5.2 cases per 1000 in 1999.
 Societies such as New Zealand, Taiwan and USA show
increasing prevalence.
 More prevalent among African American Males than
European American males.

11. Causes of Gout (Etiology)
 High levels of uric acid circulating in the blood, which
can cause needle-shaped urate crystals to settle in the
tissues of the joints as well as the kidneys.
These crystals are sodium urate crystals which are the
end products of purine matabolism.
this deposition first causes acute then chronic gouty
arthritis.

12. Causes of Gout (Etiology)
 Inheritance of certain genes
This inherited gene causes an abnormality in the
enzyme of purine metabolism (primary gout).
Several X-linked mutations have been identified in the
PRPP synthetase gene which results in the enzyme
having either:
 Increased Vmax for the production of PRPP
 A lower Km for ribose 5-phosphate
 Decreased sensitivity to its purine nucleotide inhibitors
The overall result is increased purine production
resulting in high levels of plasma uric acid.

13. Causes of Gout (Etiology)

14. Causes of Gout (Etiology)
Secondary Gout may be caused from cancer, chronic renal
failure or any of the following:
 From being overweight and eating a rich diet.
 Lymphoma: a usually malignant tumour of lymphoid
tissue
 Leukemia: an acute or chronic disease characterized by an
abnormal increase in the number of white blood cells in
bodily tissues
 hemolytic anemia: anemia caused by excessive destruction
of red blood cells.
The latter three may be the underlying cause of the uric
acid buildup that results in gout.

15. Causes of Gout (Etiology)
 Chronic exposure to high levels of lead decreases the
body’s excretion of urates, allowing uric acid to
accumulate in the blood.

16. Any metabolic aberration which reduces the rate of synthesis of AMP or
GMP from IMP, or from purine bases by the salvage mechanism, or which
accelerates the removal of nueleotides into macromolecules or through
increased catabolism, may in theory result in reduced intracellular
concentrations of regulatory nucleotides and release of the
amidotransferase from inhibition. This would permit excessive synthesis of
phosphoribosylamine and ultimately of uric acid.
The turnover of nucleic acids and coenzymes ultimately results
in production of free purine bases, chiefly adenine, hypoxanthine and
guanine, which are largely recycled into purine ribonucleotides and nucleic
acid once again, by reactions sometimes referred to as salvage
pathways. A fraction of hypoxanthine and guanine is further oxidized
to uric acid, which is a biologically inert end product excreted largely
in the urine.

17. tudies of the rates of production of uric acid in subjects
with primary gout have disclosed evidence of excessive
synthesis of purines in a large percentage of patients.
On a diet very low in purines, 24 per cent excreted
quantities of urate in urine in excess of 590 mg per day,
the upper limit of the normal range.
ric acid is produced by xanthine oxidase from xanthine
and hypoxanthine, which in turn are produced from
purine. Uric acid is more toxic to tissues than either
xanthine or hypoxanthine.

18. n human blood plasma, the reference range of uric acid
is between 3.6 mg/dL and 8.3 mg/dL
urines are found in high amounts in animal internal
organ food products, such as liver. A moderate amount
of purine is also contained in beef, pork, poultry, fish
and seafood, asparagus, cauliflower, spinach,
mushrooms, green peas, lentils, dried peas, beans,
oatmeal, wheat bran and wheat germ.
xamples of high purine sources include: sweetbreads,
anchovies, sardines, liver, beef kidneys, brains, meat
extracts (e.g Oxo, Bovril), herring, mackerel, scallops,
game meats, and gravy.

19. 1. Turnover of nucleic acid and coenzymes results in
the production of free purine bases (Adenine,
hypoxantine and guanine). These bases go to the
salvage pathways.
2. Decreased activity of HGPRT which catalyzes a
reaction of hypoxantine, guanine and adenosine
with PRPP to give IMP, GMP and AMP results in the
buildup of PRPP and reduced levels of IMP,GMP
and AMP.
3. Hence hypoxanthine, guanine and adenine would
go towards the production of xanthine which is
oxidixed to uric acid – leading to hyperuricemia.
4. N.B. InVon Geirke Disease, G6P is shunted to the
HMP pathway – lead to the increased production of
R5P – leading to the increased production of PRPP.

23. Signs & Symptoms
 Acute gout attacks: a rapid onset of pain in the
affected joint followed by warmth, swelling, reddish
discoloration, and marked tenderness.
 Bursitis
 The small joint at the base of the big toe is the most
common site of an acute gout attack. Other joints
that can be affected include the ankles, knees, wrists,
fingers, and elbows.
 Intense tenderness: even a blanket touching the skin
over the affected joint can be unbearable

24.  These painful attacks usually subside in hours to days,
with or without medication
 Symptoms related to Chronic Gout
 Chronic (tophaceous) gout: nodular masses of uric
acid crystals (tophi) deposit in different soft tissue
areas of the body
 Such as: fingers, at the tips of the elbows, and around
the big toe;
 Rarely in ears, vocal cords and around the spinal cord

28. *Physical examination and medical history
*Measuring blood uric acid levels
*Examination and analysis of synovial fluid
*Radiography

29. DIAGNOSIS
Physical examination and medical history
 patient’s description of symptoms
Gout is more likely if:
- Arthritis first appears in the big toe than if it first appears
elsewhere
- Onset of symptoms (pain and swelling) takes days or
weeks .symptoms which take hours to develop probably
indicate a disorder other than gout.
- Abnormal enlargements in joints that had been affected by
previous injury or osteoarthritis are possible signs of gout

30. DIAGNOSIS
Measuring blood uric acid levels
 A blood test is usually given for measuring uric acid and
detecting hyperuricemia. A low level of uric acid in the
blood makes a diagnosis of gout much less probable, and a
very high level increases the likelihood of gout.
• Uric acid levels in the blood during an attack of gout can lie
within or below the normal range
• or
• Hyperuricemia may be prevalent in population and doesn’t
necessarily indicate gout.

31. DIAGNOSIS
Examination of synovial fluid
 Examination of synovial fluid is the most accurate method for
diagnosing gout.
 Synovial fluid analysis
The sample is examined through a microscope under polarized
light. This special light will reveal the presence of monosodium
urate (MSU) crystals, which will nearly always confirm a
diagnosis of gout.
Examination of aspirated joint fluid can rule out other disorders
that mimic gout, such as septic arthritis and pseudogout.

32. DIAGNOSIS
Uric acid crystals under polarized light

33. DIAGNOSIS
 Occasionally, patients with gout may present without
uric acid crystals in the synovial fluid aspirate.
However, aspiration repeated five hours to one day
later shows crystals in the synovial fluid of most of
these patients

34. DIAGNOSIS
Radiography
 is not very useful in diagnosing initial attacks of acute
gouty arthritis. The radiographic findings are
generally nonspecific, consisting of soft tissue
swelling around a joint.
 Bony abnormalities indicate the presence of chronic
gout.
 In general, gout must be untreated or inadequately
treated for approximately 12 years before chronic
arthritis and bony erosions are seen on radiographs.

35. DIAGNOSIS
Radiograph showing sharply "punched-out" bony
defects of the distal radius and proximal phalange of
the middle finger

37.  There are two essential concepts behind the
treatment of Gout:
1. Its is critical in stopping the inflammation caused by
the gouty arthritis.
2. It is vital in addressing the long term management of
the disease in order to prevent further attacks and
shrink crystal deposits.

38.  There are basically three ways of treating Gout:
1. Self Care
3. Medications
5. Surgery

39. Self Care
 Take medications as prescribed.
 While a joint is hot and swollen, aggravation should
be prevented to so as to reduce further discomfort.
The following would be helpful:
 Using of a cane or similar support to keep your weight
off that joint.
 Keep the swollen joint elevated above your chest as
much as possible.
 Ice packs can be helpful in relieving pain and reducing
inflammation.
 Maintaining adequate hydration is key for minimizing
attacks and decreasing the formation of kidney
stones.

40.  Reduce the consumption of alcohol since:
 It is known to have a diuretic effects and can contribute
to dehydration and precipitate the acute gout attack.
 Affects uric acid metabolism resulting in
hyperuricemia.
 Dietary changes can help reduce the amount of uric
acid in the blood;
 Purine rich food should be avoided (shellfish and organ
meats such as liver, brains, kidneys, and sweetbreads)

41. Medication
 There are three aspects/lines of treatment of
gout with medication:
 Pain relievers such as acetaminophen (Tylenol) or
other more potent analgesics are used to manage
pain.
 The exact mechanism of action of acetaminophen is
not known. Acetaminophen relieves pain by elevating
the pain threshold, that is, by requiring a greater
amount of pain to develop before a person feels it.

42.  Anti-inflammatory agents such as NSAIDS,
colchicine, and corticosteroids, used to decrease
joint inflammation.
 NSAIDS such as:diclofenac, etoricoxib,
indomethacin, ketoprofen and naproxen.
 Most of these drugs function by inhibiting the
COX-2 resulting in the reduction of prostaglandins
production.

43.  Colchicine is useful in suppressing the inflammation.
The exact mechanism of action of colchicine is not
known but is speculated that it impairs the motility of
granulocytes and hence prevent the inflammatory
phenomena that initiate an attack or it may involve
reduction in uric acid deposition leading to a
reduction in the inflammatory response. Colchicine is
not an analgesic (pain killer), but it reduces pain in
acute gouty arthritis.

44.  Corticosteroids such as prednisone a synthetic
corticosteroids mimic the action of cortisol
(hydrocortisone), the naturally-occurring corticosteroid
produced in the body by the adrenal glands.
Corticosteroids are potent anti-inflammatory effectors.
 Prednisone is inactive in the body and, in order to be
effective, first must be converted to prednisolone by
enzymes in the liver. Therefore, prednisone may not work
as effectively in people with liver disease whose ability to
convert prednisone to prednisolone is impaired.
 They function by inhibiting phospholipase A2 the enzyme
responsible for the release of Archidonic acid from
membrane phospholipids – the precursor for
prostaglandins.

45. • Medications for managing the chronic underlying
metabolic derangement that causes hyperuricemia and
gout. That is, medications that reduce the elevated levels
of uric acid in the blood.
• These medication are taken over prolonged periods to
lower blood uric acid level.
• Medicines used to lower blood uric acid level work either
by increasing the kidney's excretion of uric acid or by
decreasing the body's production of uric acid from the
purines in foods.
• These medicines are generally not started until after the
inflammation from acute gouty arthritis has subsided
because they can worsen the attack. If they are already
being taken prior to the attack, they are continued and
only adjusted after the attack has resolved.

46.  Allopurinol lowers the blood uric acid level by
preventing uric acid production. It acts by blocks the
metabolic conversion from purines by inhibiting
xanthine oxidase, the enzyme responsible for the
conversion of xanthine to uric acid.
 Probenecid (Benemid) and sulfinpyrazone
(Anturane) are medications that are commonly used
to decrease uric acid blood levels by increasing the
excretion of uric acid into the urine.
 These act by preventing the reabsorption of uric acid
by the kidney and hence increasing its excretion from
the body in the urine

47. Surgery
 Surgery is rarely needed for gout unless significant
joint damage has occurred from lack of effective
treatment

48. Prevention
The key to prevent gout is to maintain the
concentration of uric acid within the normal
range (7.0 mg/dL),this can be achieved by:
 Avoiding excessive intake of purine rich food such as
those high in proteins and fats e.g. seafood, beef,
poultry
 Maintain a healthy body weight via proper diet and
exercise.

49.  Avoid foods rich in fructose, sucrose (glucose and
fructose) especially high fructose corn syrup (a
common sweetener in soft drinks which results in
hyperuricemia), and diuretic foods or drugs( increases
urination).
 Restrict your intake of alcohol, especially beer(high in
guanosine), on the basis that brewer’s yeast are very
rich in purine, beer also can inhibit the elimination of
uric acid and can cause dehydration which may lead
to gout.

50.  Avoid diet low in potassium(good sources: tomatoes,
potatoes,bananas,soybeans,brown rice) since a
deficiency increases urate in blood.
 Avoid consuming too much acid containing
substances
 Drink plenty of liquids, especially water, to dilute and
assist excretion of urates

51.  Maintain an adequate intake of Vitamin C since it has
been demonstrated to increase excretion on uric acid
and in turn lower serum urate levels by dissolving the
needle-like crystals that deposit themselves between
the joints and connective tissue.
 Aviod prolonged exposure to low temperature.

52. Prognosis/Outlook
 It is excellent is you are properly diagnosed and
treated.
 The optimal regimens for the treatment of acute
gout attacks and chronic gout conditions still
require further long-term studies. Research
scientists will continue to develop less toxic and
more effective medications to battle this
"scourge of the ages”.

53.  Primary Gout is almost exclusively a disease of adult
men because their kidneys excrete uric acid less well,
and return more to blood, than do the kidneys of
women and children.
 In adult men urate already circulates at levels close to
the maximum before crystals will form

54. References
 http://www.emedicinehealth.com/gout/page9_em.htm
 http://www.medicinenet.com/gout/page5.htm
 http://books.google.gy/books?id=sFG3fyc5R_8C&dq=Gout