gout: Purine-rich food-> precipitation questions Best answer on the web
January 9, 2009 on 7:23 am | In mybachcars.com |
gout: Purine-rich food-> precipitation questions Best answer on the web 2. dietary intake of foods containing purines
a. How long after a purine-rich meal will uric acid appear in my bloodstream
b. what controls the rate at which dissolved uric acid will precipitate out into a joint c. what controls which joints?
As you know, with gout, you may have increased uric acid production, or decreased excretion of the uric acid. Increased uric acid production is generally caused by enzyme deficiencies, and diseases like mono and hemolytic anemia to name a few. When a person has decreased excretion of uric acid, it may be due to an unknown reason, genetics, hypothyroidism, high blood pressure, kidney damage, or medications/drugs.
In the absence of genetic disorders, it is not totally clear what triggers sodium urate crystals to collect in joints and tissues. Gout is more common in older people,especially men. About 300 people per 100,000 get gout. The rate at which the uric acid crystallizes depends on the amount in the blood, and is variable. The crystals form when there is a large amount of uric acid in the blood, when it is ?supersaturated?. Body temperature, as you will read further down in the answer affects uric acid crystal formation as well.
There is no definite timing of how quickly uric acid will accumulate in the joints or bloodstream after a meal. Some patients claim to have symptoms several hours after a rich meal, and this may be so in some. In others it may be coincidental ? the person could have had a high enough level before eating a meal that adds just enough uric acid to cause symptoms. Whether the person is well hydrated or not can also affect timing. Dehyrated people will feel symptoms more readily than folks that don?t consume plenty of water. If pressed for an approximate timing after a meal, I?d have to say 8-12 hours.
?The joints of the foot, ankle, knee, wrist, elbow, and hand are other frequently affected sites. In such cases the condition is known as polyarticular gout. More than one joint is affected in 10% to 20% of first attacks. The pain usually occurs in joints on one side of the body and it usually, although not alway in the lower extremities. People with polyarticular gout are more likely to have a more gradual onset of pain and a longer delay between attacks. They also more likely to experience a low-grade fever, loss of appetite, and a general feeling of unwellness.
The primary symptom, which usually takes eight to 12 hours to develop, is severe, sometimes crushing pain at and around the joint. In many cases the attack occurs late at night or early in the morning and announces itself by waking the sufferer. Some patients describe it as resembling a disoclated bone and one writer described it as "like walking on my eyeballs". Chills and mild fever may follow. The area can be so tender that walking and even the weight of bedsheets can be unbearable. Swelling may extend beyond the joint, indicating fluid build-up within. The skin over the affected area is often red, shiny, and tense. After a few days it may start to peel. An untreated attack will typically peak 24 to 48 hours after the initial appearance of symptoms, and subside after five to seven days, although it can last only hours to several weeks.? http://www.podlink.com/pathology/gout.htm
Uric acid does have a preference for the big toe (then called podagra)and ankle joints, and can accumulate in the rims of the ears, as well as tissues and kidneys. This is because the toe, ankle and ear rim are cooler in temperature than other joints. ?Over time, uric acid in the blood crystallizes and settles in the joint spaces, causing swelling, inflammation, stiffness, and pain. Gout usually affects the first metatarsal phalangeal joint of the big toe (hallux) or the ankle joints.? http://www.podiatrychannel.com/gout/index.shtml
?In the bloodstream, uric acid exists predominantly as a dissolved salt called monosodium urate (MSU). At 37 degrees C (normal body temperature) and at a uric acid concentration approaching 7 mg/dL, the blood plasma becomes supersaturated, and needlelike crystals of MSU form. Crystallization is governed by other factors as well. In joints, such as the knee and ankle, temperatures are cooler (29 degrees C to 32 degrees C), and MSU crystals are able to form at even lower uric acid concentrations, which explains why gout favors these joints.? http://www.podlink.com/pathology/gout.htm
?Gout can also affect the instep, ankles, heels, knees, wrists, fingers, and elbows.? http://www.diet-and-health.net/Diseases/Gout.html
?Uric acid is a substance that results from the breakdown of purines or waste products in the body. Normally, uric acid is dissolved in the blood and passes through the kidneys into the urine, where it is eliminated. If the body increases its production of uric acid or if the kidneys do not eliminate enough uric acid from the body, levels build up (a condition called hyperuricemia). Hyperuricemia may also result when a person eats too many high-purine foods, such as liver, dried beans and peas, anchovies, and gravies. Hyperuricemia is not a disease and by itself is not dangerous. However, if excess uric acid crystals form as a result of hyperuricemia, gout can develop. The excess crystals build up in the joint spaces, causing inflammation . Deposits of uric acid, called tophi, can appear as lumps under the skin around the joints and at the rim of the ear. In addition, uric acid crystals can also collect in the kidneys and cause kidney stones.?
?Gout is one of the most common forms of arthritis (joint inflammation). It appears as an acute attack often coming on overnight. Within 12-24 hours there is severe pain and swelling in the affected joint. The skin over the joint may be red and shiny.
Gout usually affects only one or two joints at a time - most often the feet and ankles. The ball of the big toe is the commonest site. Without treatment the attack subsides in a week or so and when patients first develop gout there may be intervals of many months or even years between attacks. As time goes by, these tend to become more frequent and more severe and eventually many joints may be involved, sometimes all at the same time. At this stage a state of chronic or continuous joint disease may develop with progressive joint damage, disability and crippling (chronic gout). Gout affects mostly men and is very rare in women until after the menopause when it is quite often seen. Gout is very common in New Zealand and it is particularly common in Maoris and Pacific Islanders. Some surveys have shown it to be present in up to 10% of adult males.? ?Uric acid is a chemical which is a natural part of the normal breaking down and building up of food and body tissues. The level in the blood can be measured and shows how much there is in the body overall. The condition of raised blood uric acid is called hyperuricaemia. When this is present the uric acid which is normally dissolved in the blood may, from time to time, form microscopic crystals in the joint. These crystals set up the inflammation which is called acute gouty arthritis or acute gout.? http://www.rheumatology.org.nz/nz08003.htm
?Asymptomatic (without symptoms) hyperuricemia--In this stage, a person has elevated levels of uric acid in the blood but no other symptoms. A person in this stage does not usually require treatment. Acute gout, or acute gouty arthritis--In this stage, hyperuricemia has caused the deposit of uric acid crystals in joint spaces. This leads to a sudden onset of intense pain and swelling in the joints, which also may be warm and very tender. An acute attack commonly occurs at night and can be triggered by stressful events, alcohol or drugs, or the presence of another illness. Early attacks usually subside within 3 to 10 days, even without treatment, and the next attack may not occur for months or even years. Over time, however, attacks can last longer and occur more frequently. Interval or intercritical gout--This is the period between acute attacks. In this stage, a person does not have any symptoms and has normal joint function. Chronic tophaceous gout--This is the most disabling stage of gout and usually develops over a long period, such as 10 years. In this stage, the disease has caused permanent damage to the affected joints and sometimes to the kidneys. With proper treatment, most people with gout do not progress to this advanced stage.? http://www.niams.nih.gov/hi/topics/gout/gout.htm#2
?To confirm a gout diagnosis the doctor may want to take a sample of fluid from the affected joint or from one of the lumps under the skin, to look for the presence of uric acid crystals under a microscope. Your doctor may also suggest you have an x-ray of the affected joint.? http://www.homehealth-uk.com/index.html?f=bodyfr=http://www.homehealth-uk.com/medical/gout.htmr
?Thus, hyperuricemia should be distinguished from gout, even though urate supersaturation is necessary for the expression of gout. Uric acid overproduction and diminished renal uric acid excretion are the major mechanisms resulting in hyperuricemia, and an understanding of the basis of hyperuricemia in individual gout patients is an important step in determining appropriate treatment and in identifying underlying disorders, offending drugs and toxins, and inherited enzyme defects, all of which can result in hyperuricemia and gout.? http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3051156&dopt=Citation
?The end product of purine catabolism in man is uric acid. Other mammals have the enzyme urate oxidase and excrete the more soluble allantoin as the end product. Man does not have this enzyme so urate is the end product for us. Uric acid is formed primarily in the liver and excreted by the kidney into the urine.
Urate in the blood could accumulate either through an overproduction and/or an underexcretion of uric acid. In gouts caused by an overproduction of uric acid, the defects are in the control mechanisms governing the production of - not uric acid itself - but of the nucleotide precursors. The only major control of urate production that we know so far is the availability of substrates (nucleotides, nucleosides or free bases).? http://www-medlib.med.utah.edu/NetBiochem/pupyr/pp.htm
?The problems that can results are:
Acute inflammatory arthritis
Chronic erosive and deforming arthritis
Kidney and/or bladder stones
Chronic renal disease or hypertension.?
The four stages of gout:
1 Asymptomatic hyperuricaemia
Crystals probably take a long time (months or years) to accumulate, most commonly in peripheral connective tissues in and around synovial joints, especially in the lower limbs. During this period there may well be no symptoms whatsoever. About 95% of people with hyperuricaemia will remain asymptomatic throughout their lives. 2 Acute attacks
A single peripheral joint is almost always involved in all initial episodes, and most often this is the metatarsalophalangeal joint between wrist and finger. Typically local irritation and aching proceeds to tissues becoming swollen, red, hot, shiny and extremely painful. The pain is often describes as the worst ever experienced. By 24 hours inflammation is maximal, and it then resolves slowly over a week or so, often with itching and flaking of overlying skin. 3 Intercritical gout
These are asymptomatic periods between attacks. Some never have a second attack, or perhaps after many years, but in most the second attack occurs with a year. The frequency of attacks and number of sites then increase with time, leading eventually to joint damage and chronic pain, after an average of about 10 years. 4 Chronic tophaceous gout
Large crystal deposits, or tophi, produce irregular firm nodules, predominantly around the upper surfaces of the fingers and hands, but other places as well, including forearms or Achilles tendons or ears. When untreated, these can lead to severe deformity. ?Lifestyle changes in early primary gout involve weight loss, reduction in alcohol consumption and avoidance of toxins like low-dose aspirin and lead. With diuretic-induced gout stopping the diuretic may be possible and be all that is required. The usual choice for reducing uric acid levels is allopurinol, because it inhibits xanthine oxidase and can depress new purine synthesis. Probenecid prevents proximal tubular reabsorption of urate.?
?The increase in blood uric acid results from increased purine intake (purines are precursors of uric acid), or increased turnover or production, or from decreased uric acid elimination by the kidneys, or a combination of all these (Figure 1). Though higher purine intake may play a part in high blood uric acid levels, excretion by the kidney should increase to compensate. In most (75%-90%) people with gout, clearance of uric acid by the kidney is significantly reduced. Increased uric acid production or decreased renal clearance can be secondary to other disorders? http://www.jr2.ox.ac.uk/bandolier/booth/gout/goutintr.html
?Uric acid passes through the liver, and enters your bloodstream. Most of it is excreted (removed from your body) in your urine, or passes through your intestines to regulate "normal" levels. Normal Uric acid levels are 2.4-6.0 mg/dL (female) and 3.4-7.0 mg/dL (male). Normal values will vary from laboratory to laboratory.? http://www.chemocare.com/managing/fullstory.sps?iNewsid=24583
?When we consider the many different roles purines play in our metabolism, it is not surprising that the diseases of purine metabolism are as varied, ranging from asymptomatic conditions, which are only discovered accidentally, to disorders with severe neurological abnormalities, which are ultimately fatal. As with other metabolic diseases, each disorder is caused by a defective gene which results in an enzyme with too little or too much catalytic activity. The numbered enzymes referred to below are shown in Figure 2. Purine metabolic diseases include: Gout. The most common defect of purine metabolism is one of the oldest known metabolic diseases. Gout was known to the ancient Egyptians, and was extensively studied by the Roman physician Galen (A.D. 131-200). We now know that gout is caused by overproduction of uric acid, with a consequent depositing of uric acid crystals in the joints. Several different enzyme defects cause gout, notably deficiency of HPRT (enzyme 21). Gout can be treated successfully by limiting purines in the diet and by using drugs which inhibit xanthine oxidase (enzyme 27) and, thereby, the production of uric acid? http://www.purineresearchsociety.org/
Not only joints are affected by gout:
?Kidney Stones. Kidney stones occur in between 10% and 40% of gout patients, and can occur at any time after the development of hyperuricemia. Although the stones are usually composed of uric acid, they may also be mixed with other materials.
Kidney Disease. About 25% of patients with chronic hyperuricemia develop progressive kidney disease, which sometimes ends in kidney failure. It should be noted, however, that many experts believe that chronic hyperuricemia is unlikely to be a common cause of kidney disease. In most cases, the kidney disease comes first and causes high concentrations of uric acid.
Gout and Heart Disease
Gout often accompanies heart problems, including high blood pressure, coronary artery disease, and congestive heart failure. Hyperuricemia, in fact, has been associated with a higher risk of death from these conditions. One 2001 study reported that disease activity in gout may contribute to unhealthy cholesterol and lipid levels. Some interesting evidence, however, suggests that hyperuricemia may occur as a response to inflammatory damage that occur with heart disease and may even be protective. Other Medical Conditions Associated with Gout
The following are some conditions that are associated with long-term gout:
Cataracts.
Dry eye syndrome.
Complications in the lungs (in rare cases, uric acid crystals occur in the lungs). http://www.umm.edu/patiented/articles/how_serious_gout_000093_4.htm
Protein and Purine metabolism
?Clinical problems associated with nucleotide metabolism in humans are predominantly the result of abnormal catabolism of the purines. The clinical consequences of abnormal purine metabolism range from mild to severe and even fatal disorders. Clinical manifestations of abnormal purine catabolism arise from the insolubility of the degradation byproduct, uric acid. Excess accumulation of uric acid leads to hyperuricemia, more commonly known as gout. This condition results from the precipitation of sodium urate crystals in the synovial fluid of the joints, leading to severe inflammation and arthritis. Most forms of gout are the result of excess purine or of a partial deficiency in the salvage enzyme, HGPRT. Most forms of gout can be treated by administering the antimetabolite, allopurinol. This compound is a structural analog of hypoxanthine that strongly inhibits xanthine oxidase.?
You can see on the chart on this page, that there are several purine metabolism defects that cause gout. http://web.indstate.edu/thcme/mwking/nucleotide-metabolism.html
?Patients shall maintain ideal bodyweights. Overweighted patients need to reduce weights slowly by a rate of losing 1kg in 1 month. Fast weight loss will produce purine in a large amount from tissue and result in acute syndromes. When acute syndromes occur, any weight-losing plan must be halted. Gout patients produce more purine from nuclear protein and harder to excrete them than normal people. Therefore, they shall avoid eating too much protein. The ideal intake is about to eat 1g of protein per 1kg of ideal bodyweight. In acute illness phase, patients shall choose low-purine foods (such as foods classified as the first category). The best protein source for them is egg, milk and dairy products. In non-acute illness phase, patients shall still avoid foods listed in the third category because they contain purine richly. The second category foods shall be chosen carefully and watched out in amount. Dried bean intake shall be reduced. The first category foods produce low purine and can be adopted in ordinary time. According to studies: a large amount of lipid will inhibit uric acid excretion and accelerate gout occurrence.. Therefore, use appropriate amount of oil when cooking. Try to choose plant oils. Avoid from cooking food by frying.? http://library.thinkquest.org/C0129280/e-text/treat/2.html
For a more scientific explanation:
?Pyrimidine nucleosides are not extensively cleaved by enzymes of the intestine, and the ribosylpyrimidines are absorbed intact and utilised for the synthesis of tissue nucleic acids. The known mammalian nucleosidases readily cleave inosine (ribosyl-hypoxanthine) and guanosine. Adenosine is converted by adenosine deaminase to inosine, and the net result leads to purines which are extensively catabolised to uric acid. Nucleic phosphorylases with high activity are responsible for the decomposition to free bases. A high xanthinoxidase activity in the mucosa of the small intestine oxidises most of the purine bases to uric acid [Montag et al., 1989]. Chinsky et al. (1990) found that adenosine deaminase was one of the most abundant proteins of the epithelial lining of the alimentary mucosa in mice. Levels were low at birth but achieved very high levels within the first few weeks of life. Thus dietary DNA, nucleotides, nucleosides, and bases are readily degraded in both the gastric and small intestine compartments.?
And
?Transport of nucleosides into the enterocyte occurs via both facilitated diffusion and specific Na+- dependent carrier-mediated mechanisms [Bronk and Hastewell, 1987; Jarvis, 1989]. The upper region of the small intestine has the greatest absorptive capacity. Once absorbed, most of the nucleosides and bases are rapidly degraded within the enterocyte, and catabolic products such as uric acid are excreted in the urine and intestine [Salati et al., 1984].
Despite extensive catabolism, tracer studies in animals indicate that only 2?5% of dietary nucleotides are incorporated into tissue pools, primarily within the small intestine, liver, and skeletal muscle [Burridge et al., 1976]. Incorporation into tissues is reportedly increased at younger ages. Extensive salvage of purines and pyrimidine nucleotides has been demonstrated in intestinal tissues. Adenine is the most extensively reutilised purine, particularly during the fasted state. In contrast, other purines are extensively degraded to uric acid in the gut. Further, up to 20% of orally administered adenine may be recovered unmetabolised in the portal vasculature [Salati et al., 1984]. Schubbert et al. (1994) reported that a portion of <0.1% of ingested phage M13 DNA was found as fragments (between <200 and 976 bp) in the blood stream, in liver and in different spleen cells in mice (i.e. tissues of the immune system).? http://australasia.ilsi.org/file/RPDNAinfoods.pdf
Role of Diet
Reduce Foods Containing Purines. Because uric acid levels are only minimally affected by diet, dietary therapy does not play a large role in the prevention of gout in the first place. Still, people who have suffered an attack of gout may benefit from reducing their intake of purine-rich foods if they habitually eat unusually large quantities of such foods. (Because purines are found in all protein foods, no one should eliminate all purines.)
Purine-containing foods include the following:
Beer and other alcoholic beverages.
Anchovies, sardines (in oil), fish roes, herring.
Yeast.
Organ meats (eg, liver, kidneys, sweetbreads).
Legumes (eg, dried beans, peas).
Meat extracts, consomm , gravies. ( Note: Any meat, fish, or poultry has moderate amounts of purines. And diets high in protein, particularly animal protein increase uric acid. No studies have determined the value of reducing protein in gout patients, however.) Mushrooms, spinach, asparagus, and cauliflower.
Drinking plenty of water and other nonalcoholic beverages helps remove MSU crystals from the body. Some researchers are studying the anti-inflammatory properties of green tea, which might have some benefit for gout. It should be noted, a Japanese study reported a higher association between gout and tea drinking (although the study did not describe the type of tea). Avoid Alcohol
Alcohol should be avoided, since it promotes purine metabolism and uric acid production; it also may reduce excretion of uric acid. Heavy drinking, especially binge drinking of beer or distilled spirits, should especially be avoided. http://www.umm.edu/patiented/articles/what_lifestyle_measures_can_help_prevent_gout_000093_9.htm
Regularly drinking alcohol interferes with the removal of uric acid from the body and can increase the risk for developing gout. Other risk factors include the following: Exposure to lead in the environment
High dietary intake of rich foods that contain purine (e.g., cream sauces, red meat, sardines, liver, scallops) Medications that may interfere with the body?s ability to remove uric acid (e.g., aspirin, diuretics, levodopa [used to treat Parkinson's disease]) Cyclosporine (e.g., Gengraf ), which is a medication used to suppress the body's immune system and prevent rejection after organ transplant, also increases the risk for developing gout. http://www.podiatrychannel.com/gout/index.shtml
How to Lower Uric Acid (Hyperuricaemia)
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?If in spite of all the measures above the uric acid remains high and attacks continue or become more frequent, other drugs can be used which directly lower the blood uric acid. However, it must be understood that these drugs have no effect on the actual attacks of acute gout and they must be taken on a continuous and long term basis. The dose must be adjusted by repeated checks on the blood uric acid before a permanent maintenance dose can be decided on. Once the uric acid is down within normal limits, the patient should remain free from gout provided the drug is continued. Some drugs work by increasing elimination via the kidneys and others by blocking uric acid formation. It is also very important for patients beginning such drugs to realize that for the first few months of treatment, gouty attacks can become more severe and frequent. This is usually controlled by taking one or two tablets a day of an additional drug for at least several months and if any acute attacks do appear they must be treated in the usual way and the long term medicines continued.? http://www.rheumatology.org.nz/nz08003.htm
Here are some illustrations of purine metabolism:
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http://www.med.unibs.it/~marchesi/purine_degradation.gif
http://sites.huji.ac.il/malaria/maps/purine.gif
http://www.stdgen.lanl.gov/oralgen/bacteria/smut/images/map00230.gif
I hope this is the information you were seeking. If anything is unclear, I?ll gladly offer further assistance, before you rate this answer.
Sincerely, Crabcakes
Search Terms
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Purine metabolism
Protein breakdown + gut
Absorption + purines
Uric acid metabolism + liver
Gout metabolism
Gout + joints
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