it is brief introduction on Gout disease in humans its causes, prevention, treatment and management of this disease, risk factors in previous medical history etc.

1. GOUT
AN INTRODUCTION
SUBMITTED BY: ISHA SAREEN

2. CONTENTS
• What is gout?
• Its epidemiology
• History
• Silent features
• Types
• Diagnosis
• Symptoms

3. Contents(cont…)
• Prevention
• Diet recommended
• Medicines
• Over the counter remedies

4. What is gout?
• Gout (metabolic arthritis) is a disease created by a
buildup of uric acid. In this condition, crystals of
monosodium urate or uric acid are deposited on the
articular cartilage of joints, tendons and surrounding
tissues. These crystals cause inflammation and pain,
both severe. If untreated, the crystals form tophi, which
can cause significant tissue damage. Gout results from a
combination of elevated concentrations of uric acid and
overall acidity in the bloodstream. In isolation, neither
elevated uric acid (hyperuricemia) nor acidity is normally
sufficient to cause gout.

5. Its epidemiology
• Gout is a form of arthritis that affects mostly men
between the ages of 50 and 60 and women following
menopause. Citation needed
• There are different racial propensities to develop gout.
Gout is high among the peoples of the Pacific Islands,
and the Māori of New Zealand, but rare in Australian
aborigines despite the latter's higher mean concentration
of serum uric acid. In the United States, gout is twice as
prevalent in African American males as it is in European-
Americans.
• A seasonal link also may exist, with significantly higher
incidence of acute gout attacks occurring in the spring.

6. History
• van Leeuwenhoek described the microscopic
appearance of uric acid crystals.
• The first written description of gout dates from 2,600 BC,
when Egyptians noted gouty arthritis of the big toe.
Around 400 BC, the Greek physician Hippocrates also
commented on gout. Writing ca. 30 AD, Aulus Cornelius
Celsus appeared to recognize many of the features of
gout, including its link with a urinary solute, late onset in
women, linkage with alcohol, and perhaps even
prevention by dairy products. "Again thick urine, the
sediment from which is white, indicates that pain and
disease are to be apprehended in the region of joints or
viscera." and "Joint troubles in the hands and feet are
very frequent and persistent, such as occur in cases of
podagra and cheiragra.

7. History(cont…)
• These seldom attack eunuchs or boys before coition with
a woman, or women except those in whom the menses
have become suppressed. Upon the commencement of
pain blood should be let; for when this is carried out at
once in the first stages it ensures health, often for a year,
sometimes for always. Some also, when they have
washed themselves out by drinking asses' milk, evade
this disease in perpetuity; some have obtained lifelong
security by refraining from wine, mead and venery for a
whole year; indeed this course should be adopted
especially after the primary attack, even although it has
subsided.".

8. History(cont...)
• Around 200 AD, the Roman gladiatorial surgeon Galen
described gout as a discharge of the four humors of the
body in unbalanced amounts into the joints. The word
"gout" was initially used by Randolphus of Bocking,
around 1,200 AD. It is derived from the Latin word
"gutta", meaning "a drop" (of liquid).
• The Dutch scientist Antonie van Leeuwenhoek described
the microscopic appearance of urate crystals in 1679. In
1848 English physician Alfred Baring Garrod realised
that excess uric acid in the blood was the cause of gout.
• Historical treatments for gout include gin

9. Silent Features
• Gout occurs when crystals of uric acid, in the form of
monosodium urate, precipitate on the articular cartilage
of joints, on tendons, and in the surrounding tissues. Uric
acid is a normal component of blood serum. Uric acid is
more likely to form into crystals when there is
hyperuricemia, although hyperuricemia is 10 times more
common without clinical gout than with it. Gout can also
occur when serum uric acid is normal, and when it is
abnormally low (hypouricemia). Paradoxically, acute
attacks of gout can occur together with a sudden
decrease in serum uric acid, such as due to use of drugs
(uricosurics, xanthine oxidase inhibitors), or total
parenteral nutrition. However, correlation does not imply
causation. The sudden decrease may be a consequence
of abrupt formation of crystals (removing uric acid from
the serum), rather than a cause.

10. Silent features(cont..)
• Regardless of the serum concentration of uric acid,
precipitation of uric acid is markedly enhanced when the
blood pH is low (acidosis). A similar pH-sensitive effect
occurs in urine, contributing to uric acid nephrolithiasis.
• Uric acid is a product of purine metabolism, and in
humans is normally excreted in the urine. Purines are
generated by the body via breakdown of cells in normal
cellular turnover, and also are ingested as part of a
normal diet. The kidneys are responsible for
approximately two-thirds of uric acid excretion, with the
gut responsible for the rest.

11. Gout is of two types, both have different effects
• Primary
• Secondary
Types

12. Primary Gout
About 10% of people with hyperuricemia develops this.
• The high levels of uric acid in the blood are caused by
protein rich foods. Alcohol intake often causes acute
attacks of gout and hereditary factors may contribute to
the elevation of uric acid, e.g. inborn errors of purine-
pyrimidine metabolism. Typically, persons with gout are
obese, predisposed to diabetes and hypertension, and at
higher risk of heart disease. Gout is more common in
affluent societies due to a diet rich in proteins, fat, and
alcohol. It is not rare, however, to find gout among the
poorer classes, who drink large quantities of malt liquors,
and whose food is insufficient in quantity and quality.
This is known as "poor man's" gout. The consumption of
a large quantity of malt liquors by either rich or poor is a
contributing cause.

13. Primary Gout
When it follows as a consequence of other health
conditions such as renal failure, it is often regardless of
the person's lifestyle. Some studies have established a
statistical connection between gout and lead
poisoning, and a significant correlation between levels
of lead in the body and urate excretion and gout. It is
known that lead sugar was used to sweeten wine, and
that chronic lead poisoning is a cause of gout, and
condition is then known as saturnine gout, because
of its association with lead (Saturnus was the
alchemists' term for the metal lead).
Diuretics particularly thiazide diuretics) have
traditionally been blamed for precipitating attacks of
gout because they compete at the same transporter,
but a Dutch case-control study from 2006 appears to
cast doubt on this conclusion.

14. Secondary gout
• Secondary gout is a complication of other medical
conditions. Medical conditions that commonly result in
gout include:
• Metabolic syndrome (combining obesity and
hyperuricemia)
• Leukemia
• Gout also can develop as a co-morbidity of other
diseases, including polycythaemia, intake of cytotoxics,
obesity, diabetes, hypertension, renal disorders, and
hemolytic anemia. Gout is an important complication in a
minority of solid organ transplant.
• Because some approved treatments for these other
conditions also reduce serum uric acid, individualized
treatment of gout has the potential to improve outcome.

15. diagnosis
• Clinically, gout can be hard to distinguish from several
other conditions, including chondrocalcinosis.
Chondrocalcinosis is a very similar disease, caused by
deposition of calcium pyrophosphate rather than uric acid.
• A definitive diagnosis of gout requires aspiration of
synovial fluid from the affected joint or tissue. The fluid is
examined by light microscopy for crystals of monosodium
urate intracellular within polymorphonuclear leukocytes.
The urate crystal has a needle-like morphology and
strong negative birefringence under polarised light. This
test may be difficult to perform, and a trained observer
does better in distinguishing this crystal from others. Many
physicians do not perform this test, relying instead on a
variety of less specific clinical signs and laboratory tests.

16. Diagnosis(cont…)
• The most informative clinical signs are the presence of
classic podagra (sudden, unexplained swelling and pain
of the big toe joint on just one foot) and the presence of
tophi. Gouty tophi, particularly when not located in a
joint, can be mistaken for basal cell carcinoma or other
neoplasm.
• Hyperuricemia is a common feature of gout, so its
presence supports a diagnosis of gout. However, gout
can occur without hyperuricemia. Hyperuricemia is
defined as a plasma urate (uric acid) level greater than
420 μmol/L (7.0 mg/dL) in males, or 380 μmol/L in
females. However, a high uric acid level does not
necessarily mean a person will develop gout. Urate is
within the normal range in up to two-thirds of cases.If
gout is suspected, the serum urate test should be
repeated once the attack has subsided

17. Diagnosis(cont…)
• . Other blood tests commonly performed are full blood
count, electrolytes, renal function, thyroid function tests
and erythrocyte sedimentation rate (ESR). This helps to
exclude other causes of arthritis, most notably septic
arthritis, and to investigate any underlying cause for the
hyperuricaemia.
• Ultrasound imaging (US) can be helpful. US signs of
gouty joints include a double-contour appearance of the
cartilage and a snowstorm appearance of the synovial
membrane. US can also be used to guide aspiration.

18. symptoms
Gout is characterized by excruciating, sudden,
unexpected, burning pain, as well as swelling, redness,
warmth, and stiffness in the affected joint. This occurs
most commonly in men's toes but can appear in other
parts of the body and affect women as well. Low-grade
fever may also be present. The patient usually suffers
from two sources of pain. The crystals inside the joint
cause intense pain whenever the affected area is
moved. The inflammation of the tissues around the joint
also causes the skin to be swollen, tender and sore if it is
even slightly touched. For example, a blanket or even
the lightest sheet draped over the affected area can
cause extreme pain.

19. Symptoms(cont…)
Gout usually attacks the big toe (approximately 75
percent of first attacks); however, it also can affect other
joints such as the ankle, heel, instep, knee, wrist, elbow,
fingers, or spine. In some cases, the condition may
appear in the joints of small toes that have become
immobile due to impact injury earlier in life; the resulting
poor blood circulation can lead to gout.
Patients with long-standing hyperuricemia (see below)
can have uric acid crystal deposits called tophi (singular:
tophus) in other tissues such as the helix of the ear.
Elevated levels of uric acid in the urine can lead to uric-
acid crystals precipitating in the kidneys or bladder,
forming uric-acid kidney stones.

20. Prevention
• Prevention of chronic gout has a different objective than
management of acute episodes (flareups). In an acute
attack the objective is to reduce pain and inflammation.
The objective of prevention is to stop any future attacks
and associated cumulative tissue damage. Prevention
strategies include reducing the supply of purine,
dissolving crystals of uric acid so the uric acid can return
to the blood, and increasing the excretion of uric acid
from the blood into the urine, without causing lithiasis
there. Prevention tactics involve careful diagnosis of the
factors contributing to the gout, followed by appropriate
use of medication, diet, and over the counter remedies.

21. Diet recommended
• The serum level of uric acid is the primary risk factor for
gout. The serum level is the result of both intake (diet)
and output (excretion). Diet should be low fat and low
protein.
• A 2004 study suggests that animal flesh sources of
purine (such as beef and seafood) greatly increase the
risk of developing gout. However, high-purine vegetable
sources (such as asparagus, cauliflower, spinach, and
green peas) did not. Dairy products such as milk and
cheese significantly reduced the chances of gout. The
study followed over 40000 men over a period of 12
years, in which 1300 cases of gout were reported.

22. Medicines
• Prescription drugs used to treat gout belong to several
functional classes. These include xanthine-oxidase
inhibitors, uricosurics, and urate oxidases.
• Allopurinol is a xanthine-oxidase inhibitor, widely used in
the prevention of attacks of gout, and well tolerated. It is
safe to use in patients with renal impairment and urate
stones. However, allopurinol and azathioprine (Imuran)
used together present a risk of a potentially fatal drug
interaction, a severe risk of allopurinol use which is of
importance to transplant patients being treated with
azathioprine for immunosuppression.

23. Medicines(cont…)
• Febuxostat ((2-[3-cyano-4-isobutoxyphenyl]-4-
methylthiazole-5-carboxylic acid) - a non-purine inhibitor
of xanthine oxidase seems to be an alternative that is
superior to allopurinol at reducing serum urate levels, but
not at reducing attacks of gout. The drug was approved
by European Medicines Agency on April 21, 2008 and
recommended for approval by the U.S. Food and Drug
Administration on November 26, 2008.
• Probenecid, a uricosuric drug, often is prescribed for
gout in conjunction with colchicine.
• Gout is suspected to be secondary to untreated sleep
apnea in some cases, caused by the release of purines
as a by-product of the breakdown of oxygen-starved
cells. Treatment for apnea can therefore be effective in
lessening incidence of acute gout attacks.

24. Medicines(cont…)
• PEG-uricase, a polyethylene glycol ("PEG") conjugate of
recombinant porcine uricase (urate oxidase), which
breaks down the uric acid deposits is being studied in
Phase III clinical trials for the treatment of severe,
treatment-refractory gout in the United States in 2006.
• Ethylenediaminetetraacetic acid (EDTA), a chelator of
lead, has successfully increased uric acid excretion.This
should be an advantageous treatment for those people
whose gout was caused by lead poisoning. Care should
be taken to increase intake of trace essential elements
since chelation often removes these elements also.

25. Over the counter remedies
• Sodium bicarbonate (baking soda) is a traditional
remedy, thought to work by raising blood pH (lowering
blood acidity). However, the added sodium may be
inappropriate for some people.
• Research from the University of British Columbia
suggests long-term coffee consumption is associated
with a lower risk of gout. Other studies extend this
benefit to tea and other caffeinated foods and drinks.
• Potassium supplements should be advantageous to treat
gout. Gout can be triggered by the same agents that
cause potassium losses such as fasting, surgery, and
potassium losing diuretics. A potassium deficiency can
increase urate levels in the blood.

26. Over the counter remedies
• Chondroitin sulfate reduces the rate of
crystallization of uric acid in urine. This
has been demonstrated in vitro but has not
been tested in clinical trial. One study
shows an opposite effect.
• Wu Jia Pi, the cortex of Siberian ginseng,
can be used intermittently between
outbreaks of gout in patients with a chronic
condition to prevent future occurrences.