1. Uric acid
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Jump to: navigation, search
For the Romanian village of Uric, see Pui.
Uric acid
Preferred IUPAC name[hide]
7,9-Dihydro-1H-purine-2,6,8(3H)-trione[citation needed]
Other names[hide]
2,6,8-Trioxypurine[citation needed]
Identifiers
CAS number 69-93-2
PubChem 1175
ChemSpider 1142
UNII 268B43MJ25
EC number 200-720-7
DrugBank DB01696
KEGG C00366
MeSH Uric+Acid
ChEBI CHEBI:27226
ChEMBL CHEMBL792
Beilstein Reference 156158
3DMet B00094
Image 1
Jmol-3D images
Image 2
SMILES
[show]
2. InChI
[show]
Properties
Molecular formula C5H4N4O3
Molar mass 168.1103 g mol-1
Exact mass 168.028340014 g mol-1
Appearance White crystals
Melting point 300 °C, 573 K, 572 °F
Solubility in water 60 mg dm-3 (at 20 °C)
log P -1.107
Acidity (pKa) 5.6
Basicity (pKb) 8.4
Thermochemistry
Std enthalpy of
o
-619.69--617.93 kJ mol-1
formation ΔfH 298
Std enthalpy of
o
-1.9212--1.91956 MJ mol-1
combustion ΔcH 298
Standard molar
173.2 J K-1 mol-1
entropySo298
Specific heat capacity, C 166.15 J K-1 mol-1 (at 24.0 °C)
(verify) (what is: / ?)
Except where noted otherwise, data are given for materials in
their standard state (at 25 °C, 100 kPa)
Infobox references
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the
formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as
ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides.
High blood concentrations of uric acid can lead to a type of arthritis known as gout. The
chemical is associated with other medical conditions like ammonium acid uratekidney stones.
3. Contents
[hide]
1 Chemistry
o 1.1 Solubility of uric acid and its salts
2 Biology
3 Genetics
4 Medicine
o 4.1 High uric acid
4.1.1 Causes of high uric acid
4.1.2 Gout
4.1.3 Lesch-Nyhan syndrome
4.1.4 Cardiovascular disease
4.1.5 Type 2 Diabetes
4.1.6 Metabolic syndrome
4.1.7 Uric acid stone formation
o 4.2 Low uric acid
4.2.1 Causes of low uric acid
4.2.2 Multiple sclerosis
4.2.3 Normalizing low uric acid
o 4.3 Oxidative stress
5 Sources
6 References
7 Further reading
8 External links
[edit] Chemistry
Uric acid is a diprotic acid with pKa1=5.4 and pKa2=10.3.[1] Thus in strong alkali at high pH,
it forms the dually charged full urate ion, but at biological pH or in the presence of carbonic
acid or carbonate ions, it forms the singly charged hydrogen or acid urate ion as its pKa2 is
greater than the pKa1 of carbonic acid. As its second ionization is so weak, the full urate salts
tend to hydrolyze back to hydrogen urate salts and free base at pH values around neutral. It is
aromatic because of the purine functional group.
As a bicyclic, heterocyclic purine derivative, uric acid does not protonate like carboxylic
acids. X-Ray diffraction studies on the hydrogen urate ion in crystals of ammomium
hydrogen urate, formed in vivo as gouty deposits, reveal the keto-oxygen in the 2 position of
a tautomer of the purine structure exists as a hydroxyl group and the two flanking nitrogen
atoms at the 1 and 3 positions share the ionic charge in the six membered pi-resonance-
stabilized ring.[2]
Thus, whereas most organic acids are deprotonated by the ionization of a polar hydrogen-to-
oxygen bond, usually accompanied by some form of resonance stabilization (resulting in a
carboxylate ion), uric acid is deprotonated at a nitrogen atom and uses a
tautomericketo/hydroxy group as an electron-withdrawing group to increase the pK1 value.
The five membered ring also possesses a keto group (in the 8 position), flanked by two
4. secondary amino groups (in the 7 and 9 positions), and deprotonation of one of these at high
pH could explain the pK2 and behavior as a diprotic acid. Similar tautomeric rearrangement
and pi-resonance stabilization would then give the ion some degree of stability. (On the
structure shown at the upper right, the NH at the upper right on the six membered ring is "1",
counting clockwise around the six membered ring to "6" for the keto carbon at the top of the
six membered ring. The upper most NH on the five membered ring is "7", counting counter
clockwise around this ring to the lower NH, which is "9".)
Uric acid was first isolated from kidney stones in 1776 by Scheele.[3] As far as laboratory
synthesis is concerned, in 1882, Horbaczewski claimed to have prepared uric acid by melting
urea hydrogen peroxide with glycine, trichlorolactic acid, and its amide. Soon after, repetition
by Eduard Hoffmann shows that this preparation with glycine gives no trace of uric acid, but
trichlorolactimide produces some uric acid. Thus, Hoffmann was the first to synthesize uric
acid.[4]
[edit] Solubility of uric acid and its salts
Generally, the water solubilitity of uric acid and its alkali metal and alkaline earth salts is
rather low. All these salts exhibit greater solubility in hot water than cold, allowing for easy
recrystallization. This low solubility is significant for the etiology of gout. The solubility of
the acid and its salts in ethanol is very low or negligible. In ethanol water mixtures, the
solubilities are somewhere between the end values for pure ethanol and pure water.
Compound Cold Water Boiling Water
Uric Acid 15000 2000
NH4HUrate - 1600
LiHUrate 370 39
NaHUrate 1175 124
KHUrate 790 75
Mg(HUrate)2 3750 160
Ca(HUrate)2 603 276
Na2Urate 77 -
K2Urate 44 35
CaUrate 1500 1440
SrUrate 4300 1790
BaUrate 7900 2700
The figures given indicate what mass of water is required to dissolve a unit mass of
compound indicated, the lower the number, the more soluble the substance in the said
solvent.[5][6][7]
[edit] Biology
5. The enzyme xanthine oxidase makes uric acid from xanthine and hypoxanthine, which in turn
are produced from purines. Xanthine oxidase is a large enzyme whose active site consists of
the metal, molybdenum, binded to sulfur and oxygen.[8] Within cells, xanthine oxidase can
exist as xanthine dehydrogenase and xanthine oxireductase, which has also been purified
from bovine milk and spleen extracts.[9] Uric acid is released in hypoxic conditions.[10]
In humans and higher primates, uric acid is the final oxidation (breakdown) product of purine
metabolism and is excreted in urine. In most other mammals, the enzymeuricase further
oxidizes uric acid to allantoin.[11] The loss of uricase in higher primates parallels the similar
loss of the ability to synthesize ascorbic acid, leading to the suggestion that urate may
partially substitute for ascorbate in such species.[12] Both uric acid and ascorbic acid are
strong reducing agents (electron donors) and potent antioxidants. In humans, over half the
antioxidant capacity of blood plasma comes from uric acid.[13] The Dalmatian dog has a
genetic defect in uric acid uptake by the liver and kidneys, resulting in decreased conversion
to allantoin, so this breed excretes uric acid, and not allantoin, in the urine.[14]
In birds and reptiles, and in some desert dwelling mammals (e.g., the kangaroo rat), uric acid
also is the end product of purine metabolism, but it is excreted in feces as a dry mass. This
involves a complex metabolic pathway that is energetically costly in comparison to
processing of other nitrogenous wastes such as urea (from urea cycle) or ammonia, but has
the advantage of reducing water loss.[15]
In humans, about 70% of daily uric acid disposal occurs via the kidneys, and in 5-25% of
humans, impaired renal (kidney) excretion leads to hyperuricemia.[16]
[edit] Genetics
A proportion of people have mutations in the proteins responsible for the excretion of uric
acid by the kidneys. Nine genes have so far been identified: SLC2A9; ABCG2; SLC17A1;
SLC22A11; SLC22A12; SLC16A9; GCKR; LRRC16A; and PDZK1.[17][18]SLC2A9 is known to
transport both uric acid and fructose.[16][19]
[edit] Medicine
In human blood plasma, the reference range of uric acid is between 3.6 mg/dL (~214 µmol/L)
and 8.3 mg/dL(~494 µmol/L) (1 mg/dL=59.48 µmol/L).[20] This range is considered normal
by the American Medical Association Manual of Style.[21] Uric acid concentrations in blood
plasma above and below the normal range are known, respectively, as hyperuricemia and
hypouricemia. Similarly, uric acid concentrations in urine above and below normal are
known as hyperuricosuria and hypouricosuria. Such abnormal concentrations of uric acid are
not medical conditions, but are associated with a variety of medical conditions.[citation needed]
Reference ranges for blood tests, comparing blood content of uric acid (shown in yellow)
with other constituents
6. [edit] High uric acid
High levels of uric acid is called hyperuricemia.
[edit] Causes of high uric acid
In many instances, people have elevated uric acid levels for hereditary reasons.
Diet may be a factor. High intake of dietary purine as well as fructose (and table sugar
which is roughly 50% fructose) can cause increased levels of uric acid.[22]
Serum uric acid can be elevated due to reduced excretion by the kidneys.[23]
Fasting or rapid weight loss can temporarily elevate uric acid levels.
Iron (Fe) activates xanthine oxidase (XO) and copper (Cu) deactivates it, so as men
accumulate Fe with age (ferritin levels rise above 45 ng/dl) and Cu levels decline as
testosterone levels drop with age (testosterone increases Cu half life), eventually the high
Fe/Cu results in more active XO and higher urate levels. Excess Fe can be eliminated
through phlebotomy (blood donation) and low Cu can be corrected through daily intake
of 2 mg Cu per day, reducing urate levels.
[edit] Gout
Excess serum accumulation of uric acid can lead to a type of arthritis known as gout.[24] This
painful condition is the result of needle-like crystals of uric acid precipitating in joints and
capillaries. Kidney stones can also form through the formation and deposition of sodium
urate microcrystals.[25]
It has also been found that men who drank two or more sugar-sweetened beverages a day
have an 85% higher chance of developing gout than those who drank such beverages
infrequently.[26]
Gout can occur where serum uric acid levels are as low as 6 mg/dL (~357 µmol/L), but an
individual can have serum values as high as 9.6 mg/dL (~565 µmol/L) and not have gout.[27]
One treatment for gout, in the 19th century, had been administration of lithium salts;[28]
lithium urate is more soluble. Today, inflammation during attacks is more commonly treated
with NSAIDs, and urate levels are managed with allopurinol.[29] Allopurinol, developed over
30 years ago by Elion et al., weakly inhibits xanthine oxidase. It is an analog of hypoxanthine
that is hydroxylated by xanthine oxireductase at the 2-position to give oxipurinol. Oxipurinol
has been supposed to bind tightly to the reduced molybdenum ion in the enzyme and thus
inhibits uric acid synthesis.[30]
[edit] Lesch-Nyhan syndrome
Lesch-Nyhan syndrome, an extremely rare inherited disorder, is also associated with very
high serum uric acid levels.[31] Spasticity, involuntary movement and cognitive retardation as
well as manifestations of gout are seen in cases of this syndrome.[32]
7. [edit] Cardiovascular disease
Although uric acid can act as an antioxidant, excess serum accumulation is often associated
with cardiovascular disease. It is not known whether this is causative (e.g., by acting as a
prooxidant ) or a protective reaction taking advantage of urate's antioxidant properties.[24][33]
The same may account for the putative role of uric acid in the etiology of stroke.[34]
[edit] Type 2 Diabetes
The association of high serum uric acid with insulin resistance has been known since the
early part of the 20th century, nevertheless, recognition of high serum uric acid as a risk
factor for diabetes has been a matter of debate. In fact, hyperuricemia has always been
presumed to be a consequence of insulin resistance rather than its precursor.[35] However, a
prospective follow-up study showed high serum uric acid is associated with higher risk of
type 2 diabetes, independent of obesity, dyslipidemia, and hypertension.[36]
[edit] Metabolic syndrome
Hyperuricemia is associated with components of metabolic syndrome. A study has suggested
fructose-induced hyperuricemia may play a pathogenic role in the metabolic syndrome.[37]
This is consistent with the increased consumption in recent decades of fructose-containing
beverages (such as fruit juices and soft drinks sweetened with sugar and high-fructose corn
syrup) and the epidemic of diabetes and obesity.[26]
[edit] Uric acid stone formation
Saturation levels of uric acid in blood may result in one form of kidney stones when the urate
crystallizes in the kidney. These uric acid stones are radiolucent and so do not appear on an
abdominal plain X-ray. Their presence must be diagnosed by ultrasound for this reason. Very
large stones may be detected on X-ray by their displacement of the surrounding kidney
tissues.
Uric acid stones, which form in the absence of secondary causes such as chronic diarrhea,
vigorous exercise, dehydration, and animal protein loading, are felt to be secondary to obesity
and insulin resistance seen in metabolic syndrome. Increased dietary acid leads to increased
endogenous acid production in the liver and muscles, which in turn leads to an increased acid
load to the kidneys. This load is handled more poorly because of renal fat infiltration and
insulin resistance, which are felt to impair ammonia excretion (a buffer). The urine is
therefore quite acidic, and uric acid becomes insoluble, crystallizes and stones form. In
addition, naturally present promoter and inhibitor factors may be affected. This explains the
high prevalence of uric stones and unusually acidic urine seen in patients with type 2 diabetes.
Uric acid crystals can also promote the formation of calcium oxalate stones, acting as "seed
crystals" (heterogeneous nucleation).[38]
[edit] Low uric acid
[edit] Causes of low uric acid
Low uric acid (hypouricemia) can have numerous causes.
8. Low dietary zinc intakes cause lower uric acid levels. This effect can be even more
pronounced in women taking oral contraceptive medication.[39]
Xanthine oxidase is an Fe-Mo enzyme, so people with Fe deficiency (the most common
cause of anemia in young women) or Mo deficiency can experience hypouricemia.
Xanthine oxidase loses its function and gains ascorbase function when some of the Fe atoms
in XO are replaced with Cu atoms. Accordingly, people with high Cu/Fe can experience
hypouricemia and vitamin C deficiency, resulting in oxidative damage. Since estrogen
increases the half life of Cu, women with very high estrogen levels and intense blood loss
during menstruation are likely to have a high Cu/Fe and present with hypouricemia.
Sevelamer, a drug indicated for prevention of hyperphosphataemia in patients with chronic
renal failure, can significantly reduce serum uric acid.[40]
[edit] Multiple sclerosis
Lower serum values of uric acid have been associated with multiple sclerosis (MS). MS
patients have been found to have serum levels ~194 µmol/L, with patients in relapse
averaging ~160 µmol/L and patients in remission averaging ~230 µmol/L. Serum uric acid in
healthy controls was ~290 µmol/L.[41] Conversion factor: 1 mg/dL=59.48 µmol/L[20]
A 1998 study completed a statistical analysis of 20 million patient records, comparing serum
uric acid values in patients with gout and patients with multiple sclerosis. Almost no overlap
between the groups was found.[42]
Uric acid has been successfully used in the treatment and prevention of the animal (murine)
model of MS. A 2006 study found elevation of serum uric acid values in multiple sclerosis
patients, by oral supplementation with inosine, resulted in lower relapse rates, and no adverse
effects.[43]
[edit] Normalizing low uric acid
Correcting low or deficient zinc levels can help elevate serum uric acid.[44]Inosine can be
used to elevate uric acid levels.[41] Zn inhibits Cu absorption, helping to reduce the high
Cu/Fe in some people with hypouricemia. Fe supplements can ensure adequate Fe reserves
(ferritin above 25 ng/dl), also correcting the high Cu/Fe.
[edit] Oxidative stress
Uric acid may be a marker of oxidative stress,[45] and may have a potential therapeutic role as
an antioxidant.[46] On the other hand, like other strong reducing substances such as ascorbate,
uric acid can also act as a prooxidant,[47] particularly at elevated levels. Thus, it is unclear
whether elevated levels of uric acid in diseases associated with oxidative stress such as stroke
and atherosclerosis are a protective response or a primary cause.[48][49]
For example, some researchers propose hyperuricemia-induced oxidative stress is a cause of
metabolic syndrome.[37][50] On the other hand, plasma uric acid levels correlate with longevity
in primates and other mammals.[51] This is presumably a function of urate's antioxidant
properties.[52]
9. [edit] Sources
In humans, purines are excreted as uric acid. Purines are found in high amounts in animal
food products, such as liver and sardines.[53] 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.[54]
Examples of high purine and Fe sources include: sweetbreads, anchovies, sardines, liver,
beef kidneys, brains, meat extracts (e.g., Oxo, Bovril), herring, mackerel, scallops, game
meats, and gravy.
Moderate intake of purine-containing food is not associated with an increased risk of
gout.[55]
Hyperuricemia
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Not to be confused with hypouricemia.
Asymptomatic hyperuricemia
Classification and external resources
Uric acid
ICD-10 E79.0
ICD-9 790.6
DiseasesDB 5375
eMedicine med/1112
10. MeSH D033461
Hyperuricemia (British English: hyperuricaemia) is a level of uric acid in the blood that is
abnormally high. In humans, the upper end of the normal range is 360 µmol/L (6 mg/dL) for
women and 400 µmol/L (6.8 mg/dL) for men.[1]
Contents
[hide]
1 Causes
o 1.1 Increased production
o 1.2 Decreased excretion
o 1.3 Mixed
o 1.4 Unclassified
2 Treatment
o 2.1 Concentration
o 2.2 pH
o 2.3 Temperature
3 Prognosis
4 Dalmatian dogs
5 Genetics
6 History
7 See also
8 References
9 External links
[edit] Causes
Many factors contribute to hyperuricemia, including: genetics, insulin resistance,
hypertension, renal insufficiency, obesity, diet, use of diuretics, and consumption of alcoholic
beverages.[2] Of these, alcohol consumption is the most important.[3]
Causes of hyperuricemia can be classified into three functional types:[4] increased production
of uric acid, decreased excretion of uric acid, and mixed type. Causes of increased production
include high levels of purine in the diet and increased purine metabolism. Causes of
decreased excretion include kidney disease, certain drugs, and competition for excretion
between uric acid and other molecules. Mixed causes include high levels of alcohol and/or
fructose in the diet, and starvation.
[edit] Increased production
A purine-rich diet is a common but minor cause of hyperuricemia. Diet alone generally is not
sufficient to cause hyperuricemia. Purine content of foods varies (see Gout). Foods high in
the purines adenine and hypoxanthine may be more potent in exacerbating hyperuricemia.[5]
11. Hyperuricemia of this type is a common complication of solid organ transplant.[6] Apart from
normal variation (with a genetic component), tumor lysis syndrome produces extreme levels
of uric acid, mainly leading to renal failure. The Lesch-Nyhan syndrome is also associated
with extremely high levels of uric acid.
[edit] Decreased excretion
The principal drugs that contribute to hyperuricemia by decreased excretion are the primary
antiuricosurics. Other drugs and agents include diuretics, salicylates, pyrazinamide,
ethambutol, nicotinic acid, ciclosporin, 2-ethylamino-1,3,4-thiadiazole, and cytotoxic
agents.[7]
The gene SLC2A9 encodes a protein that helps to transport uric acid in the kidney. Several
single nucleotide polymorphisms of this gene are known to have a significant correlation with
blood uric acid.[8]
A ketogenic diet impairs the ability of the kidney to excrete uric acid, due to competition for
transport between uric acid and ketones.[9]
Elevated blood lead is significantly correlated with both impaired kidney function and
hyperuricemia (although the causal relationship among these correlations is not known). In a
study of over 2500 people resident in Taiwan, a blood lead level exceeding 7.5 microg/dL (a
small elevation) had odds ratios of 1.92 (95% CI: 1.18-3.10) for renal dysfunction and 2.72
(95% CI: 1.64-4.52) for hyperuricemia.[10]
[edit] Mixed
Causes of hyperuricemia that are of mixed type have a dual action, both increasing
production and decreasing excretion of uric acid.
High intake of alcohol (ethanol), a significant cause of hyperuricemia, has a dual action that
is compounded by multiple mechanisms. Ethanol increases production of uric acid by
increasing production of lactic acid, hence lactic acidosis. Ethanol also increases the plasma
concentrations of hypoxanthine and xanthine via the acceleration of adenine nucleotide
degradation, and is a possible weak inhibitor of xanthine dehydrogenase. As a byproduct of
its fermentation process, beer additionally contributes purines. Ethanol decreases excretion of
uric acid by promoting dehydration and (rarely) clinical ketoacidosis.[3]
High dietary intake of fructose contributes significantly to hyperuricemia.[11][12][13] In a large
study in the United States, consumption of four or more sugar-sweetened soft drinks per day
gave an odds ratio of 1.82 for hyperuricemia.[14] Increased production of uric acid is the result
of interference, by a product of fructose metabolism, in purine metabolism. This interference
has a dual action, both increasing the conversion of ATP to inosine and hence uric acid and
increasing the synthesis of purine.[15] Fructose also inhibits the excretion of uric acid,
apparently by competing with uric acid for access to the transport protein SLC2A9.[16] The
effect of fructose in reducing excretion of uric acid is increased in people with a hereditary
(genetic) predisposition toward hyperuricemia and/or gout.[15]
Starvation causes the body to metabolize its own (purine-rich) tissues for energy. Thus, like a
high purine diet, starvation increases the amount of purine converted to uric acid. A very low
12. calorie diet without carbohydrate can induce extreme hyperuricemia; including some
carbohydrate (and reducing the protein) reduces the level of hyperuricemia.[17] Starvation also
impairs the ability of the kidney to excrete uric acid, due to competition for transport between
uric acid and ketones.[18]
[edit] Unclassified
Phosphofructokinase deficiency[19]
[edit] Treatment
Precipitation of uric acid crystals, and conversely their dissolution, is known to be dependent
on the concentration of uric acid in solution, pH, sodium concentration, and temperature.
Established treatments address these parameters.
[edit] Concentration
Following Le Chatelier's principle, lowering the blood concentration of uric acid may permit
any existing crystals of uric acid to be gradually dissolved into the blood, from whence the
dissolved uric acid can be excreted. Maintaining a lower blood concentration of uric acid
similarly should reduce the formation of new crystals. If the person has chronic gout or
known tophi, then large quantities of uric acid crystals may have accumulated in joints and
other tissues, and aggressive and/or long duration use of medications may be needed.
Medications most often used to treat hyperuricemia are of two kinds: xanthine oxidase
inhibitors and uricosurics. Xanthine oxidase inhibitors decrease the production of uric acid,
by interfering with xanthine oxidase. Uricosurics increase the excretion of uric acid, by
reducing the reabsorption of uric acid once the kidneys have filtered it out of the blood. Some
of these medications are used as indicated, others are used off-label. Several other kinds of
medications have potential for use in treating hyperuricemia. In people receiving
hemodialysis, sevelamer can significantly reduce serum uric acid,[20][21] apparently by
adsorbing urate in the gut.[21] In women, use of combined oral contraceptive pills is
significantly associated with lower serum uric acid.[22]
Non-medication treatments for hyperuricemia include a low purine diet (see Gout) and a
variety of dietary supplements. These treatments are regarded by many physicians as having
little or no efficacy. Treatment with lithium salts has been used as lithium improves uric acid
solubility.
[edit] pH
Serum pH is neither safely or easily altered. Therapies that alter pH principally alter the pH
of urine, to discourage a possible complication of uricosuric therapy: formation of uric acid
kidney stones due to increased uric acid in the urine (see Nephrolithiasis). Dietary
supplements that can be used to make the urine more alkaline include sodium bicarbonate,
potassium citrate, magnesium citrate, and Shohl's Solution (now replaced by Bicitra[23]).
Medications that have a similar effect include acetazolamide.
[edit] Temperature
13. Low temperature is a commonly reported trigger of acute gout: an example would be a day
spent standing in cold water, followed by an attack of gout the next morning. This is believed
to be due to temperature-dependent precipitation of uric acid crystals in tissues at below
normal temperature. Thus, one aim of prevention is to keep the hands and feet warm, and
soaking in hot water may be therapeutic.
[edit] Prognosis
Increased levels predispose for gout and, if very high, renal failure. The metabolic syndrome
often presents with hyperuricemia.
Persons with gout, and by inference hyperuricemia, are significantly less likely to develop
Parkinson's disease, unless they also require diuretics.[24]
[edit] Dalmatian dogs
In Dalmatian dogs, a lack of uricase (a genetic trait fixed in this breed) contributes to
hyperuricemia and corresponding hyperuricosuria.
[edit] Genetics
Hyperuricemiacosegregating with osteogenesisimperfecta has been shown to be associated
with a mutation in GPATCH8 using exomesequencing[25]
Hypouricemia
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Not to be confused with Hyperuricemia.
Hypouricemia
Classification and external resources
Uric acid
14. DiseasesDB 21432
Hypouricemia is a level of uric acid in blood serum that is below normal. In humans, the
normal range of this blood component has a lower threshold set variously in the range of
2 mg/dL to 4 mg/dL, while the upper threshold is 530 micromol/L (6 mg/dL) for women and
619 micromol/L (7 mg/dL) for men.[1]Hypouricemia usually is benign and sometimes is a
sign of a medical condition.
Contents
[hide]
1 Causes
o 1.1 Medication
o 1.2 Diet
o 1.3 Genetics
o 1.4 Medical conditions
2 Prevalence
3 Diagnosis
4 Treatment
o 4.1 Drugs and dietary supplements that may be helpful
5 Complications
6 See also
7 References
[edit] Causes
Hypouricemia is not a medical condition itself (i.e., it is benign), but it is a useful medical
sign. Usually hypouricemia is due to drugs and toxic agents, sometimes it is due to diet or
genetics, and rarely it is due to an underlying medical condition. When one of these causal
medical conditions is present, hypouricemia is a common sign.
[edit] Medication
The majority of drugs that contribute to hypouricemia are uricosurics (drugs that increase the
excretion of uric acid from the blood into the urine).[2] Others include drugs that reduce the
production of uric acid: xanthine oxidase inhibitors, urate oxidase (rasburicase), and
sevelamer.[3]
[edit] Diet
Hypouricemia is common in vegetarians due to the low purine content of most vegetarian
diets.[4] Vegetarian diet has been found to result in mean serum uric acid values as low as 239
µmol/L (2.7 mg/dL).[5] While a vegetarian diet is typically seen as beneficial with respect to
15. conditions such as gout,[5] care should be taken to avoid associated health conditions.[citation
needed]
Transient hypouricemia sometimes is produced by total parenteral nutrition.[6] Paradoxically,
total parenteral nutrition may produce hypouricemia followed shortly by acute gout, a
condition normally associated with hyperuricemia.[7][8] The reasons for this are unclear.
[edit] Genetics
Genetic mutations known to cause hypouricemia are of two kinds: mutations causing
xanthine oxidase deficiency, which reduces the production of uric acid; and mutations
causing abnormal kidney function that increases the excretion of uric acid. Collectively
known as familial renal hypouricemia, these latter mutations are of two types, involving
defects of presecretory and postsecretory reabsorption.
A genetic mutation in Dalmatian dogs causes hypouricemia due to a kidney defect that
interferes with reabsorption of uric acid. A similar mutation has been reported in a human
brother and sister.[9]
In humans, loss-of-function mutations in the gene URAT1 are associated with presecretory
reabsorption defects.[10][11][12]
[edit] Medical conditions
Medical conditions that can cause hypouricemia include:
Fanconi syndrome
Hyperthyroidism
Multiple Sclerosis[13]
Myeloma
Nephritis
Wilson's disease
[edit] Prevalence
In one study, hypouricemia was found in 4.8% of hospitalized women and 6.5% of
hospitalized men. (The definition was less than 0.14 mmol l-1 for women and less than
0.20 mmol l-1 in men.) [14]
[edit] Diagnosis
Uric acid clearance should also be performed, increase in clearance points to proximal tubular
defects in the kidney, normal or reduced clearance points to a defect in xanthine oxidase.
[edit] Treatment
Idiopathichypouricemia usually requires no treatment. In some cases, hypouricemia is a
medical sign of an underlying condition that does require treatment. For example, if
16. hypouricemia reflects high excretion of uric acid into the urine (hyperuricosuria) with its risk
of uric acid nephrolithiasis, the hyperuricosuria may require treatment.[15]
[edit] Drugs and dietary supplements that may be helpful
Inositol[citation needed]
Antiuricosurics
[edit] Complications
Although normally benign, idiopathic renal hypouricemia may increase the risk of exercise-
induced acute renal failure.[16][17][18]
What diet is recommended for high uric acid?
Wednesday, 30 June 2010
Answered by: Ms. Puja Gandhi
Nutrition Consultant
Dubai
192
Share Q. My 58 years old husband has high homocystine levels and the uric acid is 6.9 and blood
pressure is 130/90 mmHg. He takes Tozzar 50 and Metilda plus. Please suggest which fruits and
vegetables he should avoid and which oil is safe for him?
A. Purines are organic compounds, which create uric acid [photo gallery] on breakdown in the body.
While your body needs uric acid for blood vessel health and other processes, a buildup of excess uric
acid can lead to gout, diabetes and even cardiovascular disease. Purines consumed in the diet
account for about 50 percent of the uric acid produced in the body. Therefore, avoiding foods high in
purines or following a modified purine diet may help improve uric acid levels.
General guidelines are -
Restrict meat/fish/poultry intake
Avoid alcohol and processed foods
17. Lose weight if overweight
Exercise regularly
Drink 8-10 glasses of water a day
Eat plenty of fruits & vegetables
Restrict foods high in purines -
Organ meats such as liver, kidney, heart
Selected fish and shellfish
Meat & yeast extracts brewers and bakers yeast
Meat soups & stock cubes
Recommended foods to eat -
Fresh cherries, strawberries, blueberries and other red-blue berries
Bananas
Celery
Tomatoes
Vegetables including cabbage and parsley
Foods high in bromelain (pineapple)
Foods high in vitamin C (red cabbage, red bell peppers, tangerines, mandarins, oranges, potatoes)
Low-fat dairy products
Complex carbohydrates (breads, cereals)
Chocolate, cocoa
Coffee, tea
18. Since purines are found in so many foods, it’s important to understand that not all purine-source
foods affect the body in the same way. For instance, although purines are found in vegetable
sources, these purines don't cause the same amount of uric acid buildup in the body that meat
sources do. In fact, fresh fruits and vegetables reduce acid levels in the body and it is often advised
to avoid red meats, organ meats and highly processed foods. Fresh fruits and vegetables are
encouraged so the patient can increase alkalinity in the blood. Therefore, rather than attempting to
find foods that are free of purines and uric acid, its important to know how to increase the body’s
alkalinity, which naturally reduces the body’s acidity. Fresh, non-processed foods, such as fruits and
vegetables, are the way to go.
Being overweight appears to be the most common determining factor for excess uric acid
production. Therefore, it is very important to maintain a healthy weight. Consider the calorific value
of the foods that do not contain purines and aim to eat a healthy well-balanced diet. Fatty foods
such as butter and cream should be avoided. When you begin to lose weight, the kidneys are more
able to eliminate uric acid and in some cases, the production of uric acid by the liver is also reduced.
Read more at:
http://doctor.ndtv.com/faq/ndtv/fid/13620/What_diet_is_recommended_for_high_uric_acid.html?
cp
What Causes High Uric Acid?
X Marcie FitzmauriceMarcie Fitzmaurice is a copywriter, editor and proofreader from Chicago,
Illinois with 10 years experience. Her work has appeared in newspapers, web sites, catalogs, print
advertisements, direct mail pieces and more. Fitzmaurice has a Bachelor of Arts degree in English
from Augustana College in Rock Island, Illinois.
By Marcie Fitzmaurice, eHow Contributor
Print this articleHyperuricemia results when excessive amounts of uric acid are present in a person's
bloodstream. In healthy individuals, uric acid flows through the liver and into the bloodstream,
where it is either excreted in urine, or passed through the intestines to regulate levels.
Hyperuricemia may result from either poor lifestyle habits or because of other medical ailments or
treatments for such conditions. Gout and kidney stones are two medical ailments that can result
19. from high uric acid levels. Normal uric acid levels for women should be between 2.4 and 6.0 mg/dL,
while men's levels should be between 3.4 and 7.0 mg/dL.
Related Searches:
Causes of Acid RefluxHigh Blood Glucose Levels Dehydration and Kidney Function
When water and other fluids aren't consumed in adequate amounts, the kidneys won't function
properly. Uric acid won't be removed from the blood through excretion, and will build up in
abnormally high amounts. To prevent dehydration and keep the kidneys working as they should, you
ought to drink water throughout the day, and particularly when exercising or if temperatures are hot.
Purine-Rich Food
Purines, which are nitrogen-containing compounds, are either made inside the cells of the body, or
brought into the body with food. Excess purines can cause elevated levels of uric acid, which may
accumulate in tissues and form crystals, thus causing high uric acid levels in the blood. Foods high in
purines, including organ and red meats, and some seafood, should be eaten in moderation, or
eliminated completely, to keep uric acid levels in balance.
Excessive Alcohol Consumption
Alcohol, and especially beer and wine, can increase uric acid levels. In order to stabilize uric acid in
the bloodstream, you may need to eliminate alcohol.
Medications
Certain medications, such as those used to treat high blood pressure, as well as aspirin, vitamin C
and niacin among others, can produce high levels of uric acid. Chemotherapy for the treatment of
cancer can also be a cause.
Cancer
Certain cancers like non-Hodgkin's lymphoma, Hodgkin's lymphoma, leukemia and other medical
conditions, like sickle cell anemia and heart failure can cause increased breakdown of body cells and
result in hyperuricemia.
Obesity
20. Obesity can cause excessive amounts of weight to fall on the kidneys, and prevent them from
functioning properly. Losing excess weight and maintaining a healthy weight can prevent
hyperuricemia.
Read more: What Causes High Uric Acid? | eHow.com
http://www.ehow.com/about_5195926_causes-high-uric-acid_.html#ixzz1jE3FrhQo
Uric Acid Diet - 9 SecretsTo Treat Gout Naturally
Gout is one of the most painful things you can have in your life. It affects mainly the distal ends of
your joints like the fingers, foot, knee and toes. Some of the symptoms of gout are swelling, unable
to put all your weight on your leg, burning pain, redness, stiffness and plenty other nasty things.
Gout is caused by the accumulation of crystals of monosodium urate (MSU) and/or uric acid within
the surrounding tendons, tissues and cartilage of the joint. In order to control and prevent gout from
occurring, you need to have a uric acid diet.
If there is too much uric acid in the joint, it will cause acute inflammation of the joint. If you don’t
treat it fast enough, the gout can become chronic and can cause severe and permanent damage to
the surrounding tissues.
The uric acid is a by-product of purine metabolism. That is, purines are formed due to the
breakdown of particular type of foods in your body. Furthermore, it is evident that two thirds of
purine production occurs in the kidneys and the rest are formed by the liver. Everyone have purines
in the body but people will gout has an excess amount of them. As a result, a uric acid diet is focused
on reducing the amount of purines within the body.
Here are several things you need to eat or avoid if you on a uric acid diet:
1. Proteins contain bucket loads of purines in them. They are most abundant in dark meat such as
venison, beef and seafood. According to a large and respected study, it states that if you have a high
consumption of seafood and/or meat, the changes of having gout is 41% and 50%. Furthermore,
shellfish like scallop, lobster, oyster, clam, and shrimp will have more purine levels than normal fish.
Any offals like liver or brain should also be avoided.
21. 2. Vegetables that is high in protein. The above study also implicated that vegetable that has high
protein level and/or is dark green leafy vegetable have more purine concentration than any other
vegetables. These can include cauliflower, spinach, mushrooms and asparagus.
3. Eat more dairy products like milk or yogurt. Not only these are good for your bones, they have low
amounts of purine levels. In fact, studies have suggested that eating more dairy products reduces
the chances of you having gout by 44%!
4. Drink less soft drinks or anything with high sugar content. This is one of the major causes of gout
and if you drink two or more soft drink a day, you will have an 85% risk of getting gout than a person
who drinks just once a month. We are always hearing about how bad soft drinks are for your teeth
but it can also cause other problems such as gout and obesity.
5. Drink less beer and spirits. I know it’s hard to hear this, but drinking beer causes a significant risk
in getting gout. If you drink a normal can of beer every day (around about 345ml or 12 oz), you will
have a 49% increase of risk.
6. Any sweets that have high fructose level like candy, jelly and jam.
7. Drink plenty of water. Drinking more water will help your body filtrate the purines out of your
body. However, do not drink energy drinks like Gatorade as these have high fructose and therefore
high purine levels.
8. Any food that contains celery extracts or you can get them in a form of a capsule from your health
food shop. Celery is a natural anti-inflammatory. It also reduces the uric acid levels in the body.
9. New studies have suggested that tart cherries can be beneficial in preventing and treating gout. It
works by dissolving sharp edgy urine crystals within the joints.
Gout Diet - Foods to Avoid
Which Items Should You Scratch from Your Grocery List?
By Carol Eustice, About.com Guide
Updated June 27, 2011
22. About.com Health's Disease and Condition content is reviewed by the Medical Review Board
.See More About:goutdietgout foods to eatgoutpreventiongouttreatmentsgout
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Diets that are high in purines and high in protein have long been suspected of causing an increased
risk of gout -- a type of arthritis caused by high levels of uric acid in the body. Excessive uric acid can
form crystals in the joints, causing pain and inflammation). Results from a study led by Dr. Hyon K.
Choi, reported in the March 11, 2004 issue of The New England Journal of Medicine, offer an
interesting twist.
About the Study
Choi's research team followed 47,150 men with no prior history of gout over a 12-year period.
During that time, 730 men were diagnosed with gout. Study participants who consumed the highest
amount of meat were 40 percent more likely to have gout than those who ate the least amount of
meat. Study participants who ate the most seafood were 50 percent more likely to have gout.
In this specific study, though, not all purine-rich foods were associated with an increased risk of gout.
There was no increased risk associated with a diet that included:
•peas
•beans
•mushrooms
•cauliflower
•spinach
These foods are considered high in purines. Choi's team also found that low-fat dairy products
decrease the risk of gout, and overall protein intake had no effect. Ultimately, diets shown to be
connected to gout are the same kinds of diet linked to cardiovascular disease.
•The Gout Diet Quiz
Recommendations for Seafood Should Be Individualized
At this point, it may seem things are getting confusing. Isn't seafood typically recommended as part
of a diet which is healthy for the heart? Yet research has revealed that there is a strong, undeniable
link between seafood and gout. How does Choi reconcile what seems like conflicting information?
He believes "recommendations for seafood should be individualized."
Sorting Out the Myths
24. More importantly, how does a person begin to sort the myths from the facts and decide what to buy
at the grocery store? According to the University of Washington, Department of Orthopedics:
•Obesity can be linked to high uric acid levels in the blood. People who are overweight should
consult with their doctor to decide on a reasonable weight-loss program. Fasting or severe dieting
can actually raise uric acid levels and cause gout to worsen.
•Usually people can eat what they like within limits. People who have kidney stones due to uric acid
may need to actually eliminate purine-rich foods from their diet because those foods can raise their
uric acid level.
•Consuming coffee and tea is not a problem, but alcohol can raise uric acid levels and provoke an
episode of gout. Drinking at least 10 to 12 eight-ounce glasses of non-alcoholic fluids every day is
recommended, especially for people with kidney stones, to help flush the uric acid crystals from the
body.
Foods Higher in Purines
Johns Hopkins lists foods that are higher in purines:
•hearts
•herring
•mussels
•yeast
•smelt
•sardines
•sweetbreads
Foods moderately high in purines include:
•anchovies
•grouse
•mutton
•veal
•bacon
•liver
•salmon
25. •turkey
•kidneys
•partridge
•trout
•goose
•haddock
•pheasant
•scallops
Gout Medications
Mayo Clinic experts suggest that medications for gout have reduced the need for dietary restrictions,
but some modifications can decrease the severity or frequency of gout attacks. Dietary modification
may also be preferred by people who cannot tolerate gout medications
Gout
From Wikipedia, the free encyclopedia
Jump to: navigation, search
"Podagra" redirects here. For the moth genus, see Podagra (moth).
Gout
Classification and external resources
Gout, a 1799 caricature by James Gillray
ICD-10 M10
ICD-9 274.00274.1274.8274.9
26. OMIM 138900300323
DiseasesDB 29031
MedlinePlus 000422
eMedicine emerg/221med/924med/1112oph/506orthoped/124radio/313
MeSH D006073
Gout (also known as podagra when it involves the big toe)[1] is a medical condition
usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender,
hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most
commonly affected (approximately 50% of cases). However, it may also present as tophi,
kidney stones, or urate nephropathy. It is caused by elevated levels of uric acid in the
blood which crystallizes and the crystals are deposited in joints, tendons, and surrounding
tissues.
Diagnosis is confirmed clinically by the visualization of the characteristic crystals in joint
fluid. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or
colchicine improves symptoms. Once the acute attack has subsided, levels of uric acid are
usually lowered via lifestyle changes, and in those with frequent attacks allopurinol or
probenecid provide long-term prevention.
Gout has increased in frequency in recent decades affecting approximately one to two
percent of the Western population at some point in their lives. The increase is believed to
be due to increasing risk factors in the population, such as metabolic syndrome, longer
life expectancy and changes in diet. Gout was historically known as "the disease of
kings" or "rich man's disease".
Contents
[hide]
1 Signs and symptoms
2 Cause
o 2.1 Lifestyle
o 2.2 Genetics
o 2.3 Medical conditions
o 2.4 Medication
3 Pathophysiology
4 Diagnosis
o 4.1 Synovial fluid
o 4.2 Blood tests
27. o 4.3 Differential diagnosis
5 Prevention
6 Treatment
o 6.1 NSAIDs
o 6.2 Colchicine
o 6.3 Steroids
o 6.4 Pegloticase
o 6.5 Prophylaxis
7 Prognosis
8 Epidemiology
9 History
10 In other animals
11 Research
12 References
13 External links
[edit] Signs and symptoms
Gout presenting in the metatarsal-phalangeal joint of the big toe. Note the slight redness
of the skin overlying the joint.
Gout can present in a number of ways, although the most usual is a recurrent attack of
acute inflammatory arthritis (a red, tender, hot, swollen joint).[2] The metatarsal-
phalangeal joint at the base of the big toe is affected most often, accounting for half of
cases.[3] Other joints, such as the heels, knees, wrists and fingers, may also be affected.[3]
Joint pain usually begins over 2–4 hours and during the night.[3] The reason for onset at
night is due to the lower body temperature then.[1] Other symptoms that may occur along
with the joint pain include fatigue and a high fever.[1][3]
Long-standing elevated uric acid levels (hyperuricemia) may result in other
symptomatology, including hard, painless deposits of uric acid crystals known as tophi.
Extensive tophi may lead to chronic arthritis due to bone erosion.[4] Elevated levels of
uric acid may also lead to crystals precipitating in the kidneys, resulting in stone
formation and subsequent urate nephropathy.[5]
[edit] Cause
28. Hyperuricemia is the underlying cause of gout. This can occur for a number of reasons,
including diet, genetic predisposition, or underexcretion of urate, the salts of uric acid.[2]
Renal underexcretion of uric acid is the primary cause of hyperuricemia in about 90% of
cases, while overproduction is the cause in less than 10%.[6] About 10% of people with
hyperuricemia develop gout at some point in their lifetimes.[7] The risk, however, varies
depending on the degree of hyperuricemia. When levels are between 415 and 530 μmol/L
(7 and 8.9 mg/dL), the risk is 0.5% per year, while in those with a level greater than
535 μmol/L (9 mg/dL), the risk is 4.5% per year.[1]
[edit] Lifestyle
Dietary causes account for about 12% of gout,[2] and include a strong association with the
consumption of alcohol, fructose-sweetened drinks, meat, and seafood.[4][8] Other triggers
include physical trauma and surgery.[6] Recent studies have found dietary factors once
believed to be associated are, in fact, not; including the intake of purine-rich vegetables
(e.g., beans, peas, lentils, and spinach) and total protein.[9][10] The consumption of coffee,
vitamin C and dairy products as well as physical fitness appear to decrease the
risk.[11][12][13] This is believed to be partly due to their effect in reducing insulin
resistance.[13]
[edit] Genetics
The occurrence of gout is partly genetic, contributing to about 60% of variability in uric
acid level.[6] Two genes called SLC2A9 and ABCG2 have been found to commonly be
associated with gout and variations in them can approximately double the risk.[14] A few
rare genetic disorders, including familial juvenile hyperuricemic nephropathy, medullary
cystic kidney disease, phosphoribosylpyrophosphatesynthetasesuperactivity, and
hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhan
syndrome, are complicated by gout.[6]
[edit] Medical conditions
Gout frequently occurs in combination with other medical problems. Metabolic syndrome,
a combination of abdominal obesity, hypertension, insulin resistance and abnormal lipid
levels occurs in nearly 75% of cases.[3] Other conditions that are commonly complicated
by gout include: polycythemia, lead poisoning, renal failure, hemolytic anemia, psoriasis,
and solid organ transplants.[6][15] A body mass index greater than or equal to 35 increases
a male's risk of gout threefold.[10] Chronic lead exposure and lead-contaminated alcohol
are risk factors for gout due to the harmful effect of lead on kidney function.[16]Lesch-
Nyhan syndrome is often associated with gouty arthritis.
[edit] Medication
Diuretics have been associated with attacks of gout. However, a low dose of
hydrochlorothiazide does not seem to increase the risk.[17] Other medicines that have been
associated include niacin and aspirin (acetylsalicylic acid).[4] The immunosuppressive
drugsciclosporin and tacrolimus are also associated with gout,[6] the former particularly
when used in combination with hydrochlorothiazide.[18]
29. [edit] Pathophysiology
Uric acid
Gout is a disorder of purine metabolism,[6] and occurs when its final metabolite, uric acid,
crystallizes in the form of monosodium urate, precipitating in joints, on tendons, and in
the surrounding tissues.[4] These crystals then trigger a local immune-mediated
inflammatory reaction[4] with one of the key proteins in the inflammatory cascade being
interleukin 1β.[6] An evolutionary loss of uricase, which breaks down uric acid, in humans
and higher primates is what has made this condition so common.[6]
The triggers for precipitation of uric acid are not well understood. While it may
crystallize at normal levels, it is more likely to do so as levels increase.[4][19] Other factors
believed to be important in triggering an acute episode of arthritis include cool
temperatures, rapid changes in uric acid levels, acidosis,[20][21] articular hydration, and
extracellular matrix proteins, such as proteoglycans, collagens, and chondroitin sulfate.[6]
The increased precipitation at low temperatures partly explains why the joints in the feet
are most commonly affected.[2] Rapid changes in uric acid may occur due to a number of
factors, including trauma, surgery, chemotherapy, diuretics, and stopping or starting
allopurinol.[1]
[edit] Diagnosis
Gout on X-rays of a left foot.Typical location at the big toe joint. Note also the soft tissue
swelling at the lateral border of the foot.
30. Spiked rods of uric acid (MSU) crystals from a synovial fluid sample photographed under
a microscope with polarized light. Formation of uric acid crystals in the joints is
associated with gout.
Gout may be diagnosed and treated without further investigations in someone with
hyperuricemia and the classic podagra. Synovial fluid analysis should be done, however,
if the diagnosis is in doubt.[1]X-rays, while useful for identifying chronic gout, have little
utility in acute attacks.[6]
[edit] Synovial fluid
A definitive diagnosis of gout is based upon the identification of monosodium urate
(MSU) crystals in synovial fluid or a tophus.[3] All synovial fluid samples obtained from
undiagnosed inflamed joints should be examined for these crystals.[6] Under polarized
light microscopy, they have a needle-like morphology and strong negative birefringence.
This test is difficult to perform, and often requires a trained observer.[22] The fluid must
also be examined relatively quickly after aspiration, as temperature and pH affect their
solubility.[6]
[edit] Blood tests
Hyperuricemia is a classic feature of gout; gout occurs, however, nearly half of the time
without hyperuricemia, and most people with raised uric acid levels never develop
gout.[3][23] Thus, the diagnostic utility of measuring uric acid level is
limited.[3]Hyperuricemia is defined as a plasmaurate level greater than 420 μmol/L
(7.0 mg/dL) in males and 360 μmol/L (6.0 mg/dL) in females.[24] Other blood tests
commonly performed are white blood cell count, electrolytes, renal function, and
erythrocyte sedimentation rate (ESR). However, both the white blood cells and ESR may
be elevated due to gout in the absence of infection.[25][26] A white blood cell count as high
as 40.0×109/L (40,000/mm3) has been documented.[1]
[edit] Differential diagnosis
The most important differential diagnosis in gout is septic arthritis.[3][6] This should be
considered in those with signs of infection or those who do not improve with treatment.[3]
To help with diagnosis, a synovial fluid Gram stain and culture may be performed.[3]
Other conditions which present similarly include pseudogout and rheumatoid arthritis.[3]
Gouty tophi, in particular when not located in a joint, can be mistaken for basal cell
carcinoma,[27] or other neoplasms.[28]
31. [edit] Prevention
Both lifestyle changes and medications can decrease uric acid levels. Dietary and lifestyle
choices that are effective include reducing intake of food such as meat and seafood,
consuming adequate vitamin C, limiting alcohol and fructose consumption, and avoiding
obesity.[2] A low-calorie diet in obese men decreased uric acid levels by 100 µmol/L
(1.7 mg/dL).[17] Vitamin C intake of 1,500 mg per day decreases the risk of gout by
45%.[29] Coffee, but not tea, consumption is associated with a lower risk of gout.[30] Gout
may be secondary to sleep apnea via the release of purines from oxygen-starved cells.
Treatment of apnea can lessen the occurrence of attacks.[31]
[edit] Treatment
The initial aim of treatment is to settle the symptoms of an acute attack.[32] Repeated
attacks can be prevented by different drugs used to reduce the serum uric acid levels.[32]
Ice applied for 20 to 30 minutes several times a day decreases pain.[2][33] Options for
acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and
steroids,[2] while options for prevention include allopurinol, febuxostat and probenecid.
Lowering uric acid levels can cure the disease.[6] Treatment of comorbidities is also
important.[6]
[edit] NSAIDs
NSAIDs are the usual first-line treatment for gout, and no specific agent is significantly
more or less effective than any other.[2] Improvement may be seen within 4 hours, and
treatment is recommended for 1–2 weeks.[2][6] They are not recommended, however in
those with certain other health problems, such as gastrointestinal bleeding, renal failure,
or heart failure.[34] While indomethacin has historically been the most commonly used
NSAID, an alternative, such as ibuprofen, may be preferred due to its better side effect
profile in the absence of superior effectiveness.[17] For those at risk of gastric side effects
from NSAIDs, an additional proton pump inhibitor may be given.[35]
[edit] Colchicine
Colchicine is an alternative for those unable to tolerate NSAIDs.[2] Its side effects
(primarily gastrointestinal upset) limit its usage.[36][37] Gastrointestinal upset, however,
depends on the dose, and the risk can be decreased by using smaller yet still effective
doses.[17] Colchicine may interact with other commonly prescribed drugs, such as
atorvastatin and erythromycin, among others.[37]
[edit] Steroids
Glucocorticoids have been found to be as effective as NSAIDs[38] and may be used if
contraindications exist for NSAIDs.[2] They also lead to improvement when injected into
the joint; the risk of a joint infection must be excluded, however, as they worsen this
condition.[2]
[edit] Pegloticase
32. Pegloticase (Krystexxa) was approved in the USA to treat gout in 2010.[39] It will be an
option for the 3% of people who are intolerant to other medications.[39]Pegloticase is
administered as an intravenous infusion every two weeks[39] and has been found to reduce
uric acid levels in this population.[40]
[edit] Prophylaxis
A number of medications are useful for preventing further episodes of gout, including
xanthine oxidase inhibitor (including allopurinol and febuxostat) and uricosurics
(including probenecid and sulfinpyrazone). They are not usually commenced until one to
two weeks after an acute attack has resolved, due to theoretical concerns of worsening the
attack,[2] and are often used in combination with either an NSAID or colchicine for the
first 3–6 months.[6] They are not recommended until a person has suffered two attacks of
gout,[2] unless destructive joint changes, tophi, or urate nephropathy exist,[5] as it is not
until this point that medications have been found to be cost effective.[2]Urate-lowering
measures should be increased until serum uric acid levels are below 300–360 µmol/L
(5.0-6.0 mg/dL) and are continued indefinitely.[2][6] If these medications are being used
chronically at the time of an attack, it is recommended they be continued.[3]
As a rule of thumb, uricosuric drugs are preferred if there is undersecretion of uric acid,
in turn indicated if a 24-hour collection of urine results in a uric acid amount of less than
800mg. [41] They are, however, contraindicated if the person has a history of renal
stones.[41] In contrast, a 24-hour urine excretion of more than 800mg indicates
overproduction, and xanthine oxidase inhibitors are preferred.[41] Overall, probenecid
appears to be less effective than allopurinol.[2]
Xanthine oxidase inhibitors (including allopurinol and febuxostat) block uric acid
production, and long term therapy is safe and well tolerated, and can be used in people
with renal impairment or urate stones, although allopurinol has caused hypersensitivity in
a small number of individuals.[2] In such cases, the alternative drug febuxostat has been
recommended.[42]
[edit] Prognosis
Without treatment, an acute attack of gout will usually resolve in 5 to 7 days. However,
60% of people will have a second attack within one year.[1] Those with gout are at
increased risk of hypertension, diabetes mellitus, metabolic syndrome, and renal and
cardiovascular disease and thus at increased risk of death.[6][43] This may be partly due to
its association with insulin resistance and obesity, but some of the increased risk appears
to be independent.[43]
Without treatment, episodes of acute gout may develop into chronic gout with destruction
of joint surfaces, joint deformity, and painless tophi.[6] These tophi occur in 30% of those
who are untreated for five years, often in the helix of the ear, over the olecranon
processes, or on the Achilles tendons.[6] With aggressive treatment, they may dissolve.
Kidney stones also frequently complicate gout, affecting between 10 and 40% of people,
and occur due to low urine pH promoting the precipitation of uric acid.[6] Other forms of
chronic renal dysfunction may occur.[6]
33. Nodules of the finger and helix of the ear representing gouty tophi
Tophus of the knee
Tophus of the toe, and over the external maleolus
Gout complicated by ruptured tophi (exudate tested positive for uric acid crystals)
[edit] Epidemiology
Gout affects around 1–2% of the Western population at some point in their lifetimes, and
is becoming more common.[2][6] Rates of gout have approximately doubled between 1990
and 2010.[4] This rise is believed to be due to increasing life expectancy, changes in diet,
and an increase in diseases associated with gout, such as metabolic syndrome and high
blood pressure.[10] A number of factors have been found to influence rates of gout,
including age, race, and the season of the year. In men over the age of 30 and women
over the age of 50, prevalence is 2%.[34]
In the United States, gout is twice as likely in African American males as it is in
European Americans.[44] Rates are high among the peoples of the Pacific Islands and the
Māori of New Zealand, but rare in Australian aborigines, despite a higher mean
concentration of serum uric acid in the latter group.[45] It has become common in China,
Polynesia, and urban sub-Saharan Africa.[6] Some studies have found attacks of gout
34. occur more frequently in the spring. This has been attributed to seasonal changes in diet,
alcohol consumption, physical activity, and temperature.[46]
[edit] History
Antonie van Leeuwenhoek described the microscopic appearance of uric acid crystals in
1679.[47]
The word gout was initially used by Randolphus of Bocking, around 1200 AD. It is
derived from the Latin word gutta, meaning "a drop" (of liquid).[47] According to the
Oxford English Dictionary, this is derived from humorism and "the notion of the
'dropping' of a morbid material from the blood in and around the joints".[48]
Gout has, however, been known since antiquity. Historically, it has been referred to as "the
king of diseases and the disease of kings"[6][49] or "rich man's disease".[50] The first
documentation of the disease is from Egypt in 2,600 BC in a description of arthritis of the big
toe. The Greek physician Hippocrates around 400 BC commented on it in his Aphorisms,
noting its absence in eunuchs and premenopausal women.[47][51]Aulus Cornelius Celsus (30
AD) described the linkage with alcohol, later onset in women, and associated kidney
problems:
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... Joint troubles in the hands and feet are very
frequent and persistent, such as occur in cases of podagra and cheiragra. These seldom attack
eunuchs or boys before coition with a woman, or women except those in whom the menses
have become suppressed... some have obtained lifelong security by refraining from wine,
mead and venery.[52]
While in 1683, Thomas Sydenham, an English physician, described its occurrence in the
early hours of the morning, and its predilection for older males:
Gouty patients are, generally, either old men, or men who have so worn themselves out in
youth as to have brought on a premature old age - of such dissolute habits none being more
common than the premature and excessive indulgence in venery, and the like exhausting
passions. The victim goes to bed and sleeps in good health. About two o'clock in the morning
35. he is awakened by a severe pain in the great toe; more rarely in the heel, ankle or instep. The
pain is like that of a dislocation, and yet parts feel as if cold water were poured over them.
Then follows chills and shivers, and a little fever... The night is passed in torture,
sleeplessness, turning the part affected, and perpetual change of posture; the tossing about of
body being as incessant as the pain of the tortured joint, and being worse as the fit comes
on.[53]
The Dutch scientist Antonie van Leeuwenhoek first described the microscopic appearance of
urate crystals in 1679.[47] In 1848 English physician Alfred Baring Garrod realized that this
excess uric acid in the blood was the cause of gout.[54]
Diet For Uric Acid And Gout Prevention
By Pat | December 5, 2008
Food For Gout Patient And Diet For Uric Acid Kidney Stones
In order to control your uric acid levels, you need to cut down your intake of foods that are high in
purines. Purine is a substance that is obtained from many food sources and is also generated by the
body as a by product of natural processes. In turn, purines are processed by the body and broken
down into uric acid. In some cases, a problem with this process of metabolizing purine may cause
excessive levels of uric acid in the body. This cannot always be controlled, but monitoring and
controlling your intake of purine rich food is possible and is one of the best ways to control uric acid
levels.
There are many food sources of purine, but meat sources seem to have the most impact on uric acid
levels. It is therefore important that you cut down your intake of meat, especially red meat. The
much sought after “spare parts” – liver, kidney, heart etc – are unfortunately particularly high in
purine content, and should be completely avoided. Duck and goose meat also tends to be high in
purine, and should be avoided as far as possible. Sea food is usually considered extremely healthy
for almost any condition, but unfortunately for people with high uric acid levels, sea food intake
needs to be cut down as well. Fish tends to be very rich in purine, especially anchovies, salmon,
sardines, mackerel, and shell fish such as mussels.
Recommended Diet For Gout Treatment
As far as meat goes, chicken and pork, as well as most sea food other than the ones mentioned, are
quite safe. However, make sure that you do not consume an excess as compensation for the meats
that you are avoiding, or your diet will not be very useful. Certain vegetables are also high in purine,
but these somehow do not affect uric acid levels much. You can therefore eat pretty much any
vegetables you like, preferably maintaining as wide a variety as possible.
36. If you are concerned about your protein intake being too low due to the drastic cutting out of meat
from your diet, you can supplement it with eggs, milk, and milk products. This too should of course
be done within reasonable limits – eggs and milk products will not affect your uric acid levels, but an
excess could cause other problems. Finally, you should control your intake of alcohol, particularly
beer. If your uric acid levels are particularly high, you should completely cut out alcohol for a few
months, and then limit consumption to rare occasions.
Uric Acid Diet
The foods we eat play a very significant role in the quality of life that we lead. While the
consumption of a hamburger on a regular basis may not really seem like you are doing too much
wrong, apart from a little self indulgence, the impact that it will have in a few months time is
something that you will usually not consider while munching on that lovely snack. If ignored those
few months down the line, the condition can spiral out of control into a full blown case of obesity.
While the most obvious effect that obesity has on an individual is the fact that it affects the aesthetic
appeal of the person considerably, the other problems that it causes – such as heart failure, chronic
respiratory illnesses and blood pressure as well as cholesterol levels can have a significant impact on
the individuals quality of life. Just as with obesity, there are a number of other conditions that will
usually develop as a direct result of the kinds of foods you consume. For instance, gout is a very
common condition that is particularly influenced by the foods you consume.
Before getting into the details of exactly what gout is, it is important to understand exactly what uric
acid is. Uric acid is a chemical substance that is created within the body as a result o the breakdown
of substances known as purines. Under normal circumstances, this uric acid is dissolved into the
blood and is flushed out of the body through the kidneys. However, some cases will see a buildup of
uric acid within the body – giving rise to serious medical ailments such as gout and kidney disease.
Medical research has shown that the intake of foods that are high in uric acid content play a
substantial role in the development as well as aggravation of certain conditions that can have a
significant impact on the workings of the human body. The uric acid condition in the body is a very
painful and common condition – especially in older men, although it is also known to affect some
women. Understanding the various symptoms as well as causes of gout will help you understand
better the best methods of gout prevention, diet and beneficial foods, herbs and medication. There
are also a number of gout prevention tips that can be found on a number of websites on the Internet
that will share information on how you can deal with the condition better and also ensure that the
condition does not affect you significantly.
One of the most common causes of the development of gout is the lack of adequate consumption of
liquids. This will occasionally cause the kidneys to malfunction and the uric acid will not be removed
from the blood through the normal process of excretion. Another very common cause of the buildup
of uric acid in the human body is the excessive consumption of purine rich foods. Essentially nitrogen
containing compounds, these foods will cause elevated levels of uric acid – causing it to accumulate
37. in the tissues of the body and form crystals. Some of the more popularly consumed foods that
contain high levels of purines include red meat, certain types of seafood and organs. Excessive
alcohol consumption is also known to be a very significant factor in the development of uric acid
buildup within the body. Most cases of treatment will require the individual to almost completely
cease any intake of alcohol until the acid levels have been returned to normal.
Before getting into the details of how to control uric acid in the blood and human body, it helps to
understand the most prominent symptoms of the condition – thereby helping you diagnose the
condition much earlier in the chain of its development. Probably the first symptom of the
development of the condition is the swelling at the base of the big toe. However, there are a few
cases in which the first swelling can occur in some other joint in the legs. The individual is likely to
experience a significant amount of pain as soon as any kind of pressure is applied to the affected
area.
Because of the fact that gout prevention is very sought after, there are a number of uric acid diets
that have been developed all over the world to help deal with the condition. Exercise is one of the
most important, while also being one of the most overlooked, aspects of gout prevention and a
regular period of between 20 to 30 minutes every day will help significantly in helping the body
reduce the amount of uric acid it contains. The best uric acid is to consume foods that are low in
sugar and salt content. Basil is known to be a very effective substitute for salt in the event that you
are looking for something to help season the food. Increasing your intake of foods like brown rice,
whole wheat bread, fruits and vegetables will also go a long way into preventing the development of
gout in your body. Another aspect of dealing with gout that one should point out is the fact that
there is no medical cure as yet for the condition. This means that, as of yet, no chemically based
medication has been developed that can help with the condition. Any gout prevention will always
require a readjusting of the individual’s lifestyle and habits to ensure that the uric acid content in the
body is reduced substantially. Obesity is also known to play a significant role in the development of
gout because of the fact that the additional weight will, more often than not, press down on the
kidneys and cause them to malfunction – thereby causing the condition to develop further.
Exercising when one has gout can be a little painful and so it is best to include in your exercise
schedule those exercises that do not place undue stress on affected joints. Simple yoga poses and
exercises for the upper body can be very useful in remaininglimber despite suffering from gout.
Foods High in Uric Acid – a Surprising Myth
Purines from food are a source of uric acid. The foods high in uric acid table below is now replaced
by the Purine Rich Foods chart.
Foods High In Uric Acid IntroductionDietitians and nutritionists commonly measure foods high in uric
acid by measuring the total purine content of food.
38. The table below lists foods high in uric acid first with purine concentration reducing as you move
down the list. Many advisers tell gout sufferers to avoid anything over 400mg and restrict foods in
the 100-400mg range, but you should treat this advice with caution.
Firstly, you must realize that typical portion sizes vary enormously.
Be sure to calculate the amount that applies to your typical serving size from the value shown for
100 grams.
Secondly, the effect of foods high in uric acid depends on direct absorption through the digestive
tract. Most uric acid derives from the breakdown of your cells as part of normal metabolism. The
overall contribution of foods high in uric acid is debatable – figures of between 5% and 15% are
common.
Purines WarningPlease be careful about getting obsessed with the purine content of food. Though
purines in food can have a slight effect on uric acid, there are many other factors to consider. Read
more about the main food factors that can affect gout in the Gout Diet section.
Foods High In Uric Acid TableYou should use the information in the table below only as a guideline.
Many other factors, besides foods high in uric acid, affect the risk of gout attacks.
If you do feel that it is important to manage foods high in uric acid, then you should measure your
total intake. Multiply the weight of your food (in grams) by the value from the table and divide this
by 100 to give your uric acid intake in milligrams. In this way you can calculate a total intake from the
list of foods high in uric acid for every meal. You need to find the level that you can tolerate best by
trial and error.
Foods High in Uric Acid
To find a particular food quickly, use your browser Find function (usually Ctrl-F).
Food Purines
(Uric Acid
mg/100g)
Theobromine 2300
Yeast, Brewer’s 1810
Neck sweet bread, Calf’s 1260
47. Cheese, edam, 30% fat content in dry matter 7.1
Cheese, edam, 40% fat content in dry matter 7.1
Cheese, edam, 45% fat content in dry matter 7.1
Cherry, sweet 7.1
Cheese, Cheddar/Cheshire cheese, 50% fat content in dry matter 6
Search Books
Showing 1 - 3 of 7 resultsFood Composition and Nutrition Tables, 7th …
Siegfried W. Souci, W Fachmann, Heinrich Kraut (…
$164.18Food Composition and Nutrition Tables, Sixt…
Siegfried W. Souci, W Fachmann, Heinrich Kraut (…
$265.96Phytosterols as Functional Food Component…
(Hardcover - Dec 2, 2003)
$206.85123>PrivacyI took the data in this table from Food Composition and Nutrition Tables by
Souci, Fachmann, Kraut [see box on right]. Their notes for the purine data states
Purines
The total of free and bound compounds is given for each component. The “total purines” column
contains the total of all individual components calculated as uric acid.
The exact calculation of this is beyond the scope of this article, but you can easily see the relative
purine count in the table. Remember, the table of foods high in uric acid shows the number of
milligrams per 100 grams, so intake will depend on portion size.
GoutPal warns against taking these types of analysis too seriously. Firstly, gout food research
indicates that vegetable purines do not increase the risk of gout, and dairy foods can actually reduce
it. More importantly, people digest foods differently – a food that causes gout in one person might
be tolerated by another, and different food combinations have significantly different effects. There
is more information about dealing with foods high in uric acid in my Gout Diet section.
48. Various food types and their purine content.
Total
Nutr.
Purines in
Density
224 Foods (alphabetically) mg uric Min Max
in
acid/100 g
mg/MJ
(Average)
HIGHEST IN PURINES (400 mg. uric acid/100 g and higher)
Fish, sardines in oil 480 399 560 519.5
Liver, Calf's 460 837.5
Mushroom, flat, edible Boletus, dried 488 932.8
Neck sweet bread, Calf's 1260 3012.9
Ox liver 554 1013.3
Ox spleen 444 1052.6
Pig's heart 530 1382
Pig's liver 515 937.9
Pig's lungs (lights) 434 911.2
Pig's spleen 516 1208.2
Sheep's spleen 773 1702.6
Sprat, smoked 804 795.6
Theobromine 2300 1611.3
Yeast, Baker's 680 2071.3
Yeast, Brewer's 1810 1866.6
MODERATELY HIGH IN PURINES (100 to 400 mg. uric acid/100g)
Bean, seed, white, dry 128 127.1
Bean, Soya, seed, dry 190 139.1
Beef, chuck 120 192
Beef, fillet 110 216.4
Beef, fore rib, entrecote 120 185.4
Beef, muscles only 133 292.1
Beef, roast beef, sirloin 110 110 120 201.4
Beef, shoulder 110 203.9
Black gram (mungo bean), seed, dry 222 194.3
Caviar (real) 144 141.6
Chicken (breast with skin) 175 288.4
Chicken (chicken for roasting), average 115 165.8
Chicken, boiling fowl, average 159 149.2
Chicken, leg with skin, without bone 110 152.2
Duck, average 138 146.2
![Uric acid
From Wikipedia, the free encyclopedia
Jump to: navigation, search
For the Romanian village of Uric, see Pui.
Uric acid
Preferred IUPAC name[hide]
7,9-Dihydro-1H-purine-2,6,8(3H)-trione[citation needed]
Other names[hide]
2,6,8-Trioxypurine[citation needed]
Identifiers
CAS number 69-93-2
PubChem 1175
ChemSpider 1142
UNII 268B43MJ25
EC number 200-720-7
DrugBank DB01696
KEGG C00366
MeSH Uric+Acid
ChEBI CHEBI:27226
ChEMBL CHEMBL792
Beilstein Reference 156158
3DMet B00094
Image 1
Jmol-3D images
Image 2
SMILES
[show]](https://image.slidesharecdn.com/uricacid-130305074855-phpapp02/85/Uric-acid-1-320.jpg)
![InChI
[show]
Properties
Molecular formula C5H4N4O3
Molar mass 168.1103 g mol-1
Exact mass 168.028340014 g mol-1
Appearance White crystals
Melting point 300 °C, 573 K, 572 °F
Solubility in water 60 mg dm-3 (at 20 °C)
log P -1.107
Acidity (pKa) 5.6
Basicity (pKb) 8.4
Thermochemistry
Std enthalpy of
o
-619.69--617.93 kJ mol-1
formation ΔfH 298
Std enthalpy of
o
-1.9212--1.91956 MJ mol-1
combustion ΔcH 298
Standard molar
173.2 J K-1 mol-1
entropySo298
Specific heat capacity, C 166.15 J K-1 mol-1 (at 24.0 °C)
(verify) (what is: / ?)
Except where noted otherwise, data are given for materials in
their standard state (at 25 °C, 100 kPa)
Infobox references
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the
formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as
ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides.
High blood concentrations of uric acid can lead to a type of arthritis known as gout. The
chemical is associated with other medical conditions like ammonium acid uratekidney stones.](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)