If anyone wanders by in the next week or so, plesae read and tell me if you understand what I'm talking about. Pwease.
This is my chem project on Gout.
I know it seems like a lot but...
Introduction: What is Gout?
Gout (also known as gouty arthritis, podogra in Greek) is a form of arthritis that is characterized by the accumulation of uric acid crystals in the joints. It occurs most often as monoarthritis, effecting only one joint, and it occurs most often in the feet, particularly the first metatarsal phalangeal joint of the big toe.
The Causes of Gout
Uric acid is the end product of the metabolism of purines in the body. Since humans do not have the enzyme urease to degrade uric acid, the body must excrete the urate in urine. If the uric acid is not excreted at a sufficient rate, an excess amount will build up in the body increasing the concentration of urate in the bloodstream. This results in a condition called hyperuricemia. A diet that is rich in purine such as shellfish and organ meat, alcohol, as well as various medications can cause hyperuricemia. This condition may also be triggered by the kidney’s inability to remove uric acid from the body. The buildup of uric acid can cause the formation of urate crystals. If the crystals deposit in the joints, they body’s immune system will respond by attack the joint causing excruciating pain — a symptom of gout.
Gout is classified as primary or secondary gout; 90% of all cases are primary gout and 10% is secondary gout. Primary gout occurs more often in men between 30 and 60 years of age. Secondary gout occurs equally in both men and women who are over the age of 65. 80%-90% of primary gout is idiopathic, where there is no known cause while the remaining cases are caused by genetic diseases that elevate the uric acid level in the body or enzyme defects. Secondary gout can be caused by a variety of factors including kidney diseases and medication.
The Symptoms, Triggers and Stages of Gout
Gout can be triggered by the overindulgence of alcohol and/or purine rich foods, surgery, crash diets, joint injury, sudden and sever illnesses and chemotherapy. Gout patients display symptoms such as sudden and excruciating pain, inflammation, redness, tenderness, swelling and stiffness in the joints. Low-grade fever may also accompany the other symptoms. The symptoms can develop within a day and if left untreated, gout can damage joints and cause disability. A patient who has hyperuricemia for a long time may develop tophi — uric acid crystal deposits in tissues that are not necessarily around the gout affected joint. In primary gout, acute attacks are common and tophi develop late while in secondary gout, acute attacks are less common and tophi develop early. Kidney stones may also be formed if the uric acid react with calcium in the body and form calcium urate.
There are four stage of gout:
1. Asymptomatic hyperuricemia: A long period (varying from months to years) in which urate crystals collect in peripheral connective tissues and around synovial joints (joints where two bones meet.) 95% of people who has hyperuricemia will not develop the symptoms of gout.
2. Acute Attack: Almost always involving a single joint in the initial episode. Initial irritation of tissues will become swollen, hot, red, shiny and extremely painful. After about 24 hours, inflammation is at its peak but it will subside over a week. The irritated skin will often itch and flake.
3. Intercritical Gout: The period between attacks where the patient is not displaying any signs or symptoms of gout. While some patients may never have another attack or until many years later, most have a second attack within a year. With repeated attacks, gout, on average over the span of a decade, causes joint damage and chronic pain.
4. Chronic Tophaceous Gout: Gout attacks may become more frequent and affects more than one joint. Tophi (large crystal deposits,) produce nodules and if left untreated can cause joint deformities. Advanced chronic gout may also cause kidney damage, hypertension and kidney stones.
The Chemistry of Gout
When the body breakdown cells, purines (Guanine and Adenine) from DNA and RNA undergo catabolism and form uric acid. The guanine nucleotides (GMP) are hydrolyzed to form guanosine which then under goes phosphorolysis to form guanine and ribose 1-P. The guanine then releases an ammonium ion to become Xanthine. Adenine nucleotides (AMP) are deaminated (loses an amino group) in the presence of the enzyme adenylate deaminase and forms IMP - inosine monophosphate. The IMP then undergoes hydrolysis to become Inosine, which is then phosphorolysized to turn into hypoxanthine. Through the enzyme xanthine oxidase, hypoxanthine forms hydrogen peroxide as a byproduct and xanthine is the final product.
Xanthine is oxidized by oxygen with the presence of xanthine oxidase. Hydrogen peroxide and uric acid (which ionize into urate ions and hydrogen ions in the bloodstream) are produced. In a healthy person, hydrogen peroxide is degraded by catalase and 66% to 75% of urate that was created is filtered out by the kidneys; the rest are eliminated by the gastrointestinal tracts. The normal plasma urate level is 3-7 mg/dL for men and 2-6 mg/dL for women.
Hyperuricemia is a condition in which the plasma urate level is higher than 7 mg/dL. When the plasma is supersaturated with urate, it can remain stable in this state and there would be no reaction. However the temperature and the pH of the blood can easily trigger the soluble sodium urate to form crystals. This creates an equilibrium reaction in the bloodstream that forms monosodium urate from sodium and urate ions. As the concentration of urate ions rises, the equilibrium will shift towards the sodium urate side and crystals will form.
NaC5H3N4O3(s) ↔ Na+(aq) + C5H3N4O3-(aq)
At the concentration of 7mg/dL monosodium urate reaches its solubility limit in the plasma. At 8mg/dL monosodium urate will likely start precipitating in tissues. The increase in the amount of uric acid in the bloodstream will decrease the normal blood pH of 7.4 and at the pH of 7, more than 90% of the uric acid exists as the monosodium urate crystals. When the pH is lower than 6, monosodium urate becomes insoluble and will form a precipitate in the blood.
The solubility of monosodium urate is also dependent on the temperature. At body temperature (37 °C) the maximum solubility of monosodium urate is 6.8 – 7 mg/dL. If the temperature is lowered to 30°C the solubility becomes 4.5 mg/dL. The variation of the solubility due to the temperature is what causes tophi to form in distal extremities such as the ear. The presence of urate crystals triggers an autoimmune response and causes inflammation due to the white blood cell activities — a gout attack.
Even though hyperuricemia is required to form urate crystals, not all people who have hyperuricemia will develop gout, nor will a patient have an elevated level of uric acid at the time of a gout attack. Other biological substances, such as IgG also influence the formation of urate crystals.
Risk Factors:
Conditions that increase the chances of a person getting gout include:
š Age and Gender: In primary gout, men are more susceptible than women. Women who has gone through menopause has an increased chance of getting gout which is why secondary gout occurs equally in men and women.
š Inheritance: Genetic diseases which causes high levels uric acid also makes people vulnerable to gout; 6 – 18% of gout patients have a family history of gout.
š Diet: Consuming food rich in purine may cause gout. Alcohol intake interferes with the body’s ability to filter out the excess uric acid and causes hyperuricemia.
š Environmental Causes: Exposure to high levels of lead increases the amount of uric acid in the body.
š Medications: includes low-dose aspirin, diuretics such as hydrochlorothiazide, levodopa used to treat Parkinsons disease and immunosuppressant drugs such as cyclosporine and tacrolimus may increase the level of uric acid.
š Physical and Medical conditions: Those who are obese, have a thyroid condition, high blood pressure or high cholesterol levels and those who have kidney conditions are also at risk of getting gout. Diabetes and sickle cell anemia can also increase the patient’s chance of getting gout.
Diagnosis:
Since patients with hyperuricemia do not necessarily develop gout nor do all gout patients have an elevated level of uric acid in their blood, diagnosis of the disease cannot be based off a simple blood test. When the joint is inflamed, a physician will typically perform a joint aspiration to confirm the diagnosis of gout. A needle is inserted into the inflamed joint and synovial fluid is extracted for analysis. A pathologist examines a wet mount of the synovial fluid and looks for uric acid crystals. Urate crystals are characterized by a strong negative bifrigence (having two refractive indexes) under polarized microscopy and they are shaped like needles. If the crystals are present, the diagnosis for gout can be confirmed. The synovial fluid should also contain an elevated level of white blood cells (polymorphonuclear leukocytes), between 7,000-10,000 x 103 per microliter, due to the inflammation. If the crystals are not present in the synovial fluid and tophi are present, the physician may have to surgically remove the tophi to look for urate crystals.
Other methods that may be used in diagnosing gout includes physical examination and X-ray. Various bloods tests such as complete blood cell count, uric acid test, serum creatinine, erythrocyte sedimentation rate, blood urea nitrogen and serum uric acid levels might be performed. The blood tests are usually used to eliminate other forms of arthritis.
The American College of Rheumatology has 11 criteria for gout.
1. More than one attack of active arthritis
2. Maximum inflammation develops within one day
3. Oligoarthritis attack
4. Redness observed over joint
5. First metatarsalophalangeal joint painful or swollen
6. Unilateral first metatarsalophalangeal joint attack
7. Unilateral tarsal joint attack
8. Tophus (proven or suspect)
9. Hyperuricaemia
10. Asymetrical swelling within a joint on radiography
11. Complete termination of an attack
Meeting six or more of the criteria can validate the diagnosis of gout.
Differential Diagnosis:
Many other illness have similar symptoms as gout, those include:
š Calcium Pyrophosphate Deposition Disease
š Primary Osteoarthritis
š Psoriatic Arthritis
š Musculoskeletal Reiter Syndrome
š Rheumatoid Arthritis
š Septic Arthritis
š Idiopathic bursitis
š Spondyloarthropathy
š Stress fracture
š Pseudogout (Calcium Pyrophosphate Dihydrate Crystal Deposition Disease)
The only way to confirm that a patient suffers from gout is through observing synovial fluids under a microscope.
Treatment:
Treatment of gout involves relieving joint pains, decreasing inflammation of the joints and decreasing the level of uric acid in the blood. Acetaminophen such as Tylenol® can be used to relieve gout pain while acetylsalicylic acid (Asprin®) should be avoided because it prevents the kidneys from excreting uric acid. Non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (Indocin®), naproxen (Naprosyn®) and ibuprofen (Advil®, Motrin®) can reduce inflammation and pain in the joints of an acute gout attacks. While NSAIDs provide the fastest relief for the symptoms of gout, patients may not be able to use those medications because NSAIDs can cause stomach pain, bleeding, diarrhea and ulcers.
For severe cases of gout or for patients who cannot take NSAIDs, physicians can prescribe corticolsteroids such as prednisone, which can be administered directly to the joint through an injection with a needle. Corticosteroids work by preventing the release of phospholipids and decreasing eosinophil action and thus reduces inflammation. Side effects of corticosteroids include the thinning of bones, poor healing of wounds and interference with the immune system’s ability to fight infections.
Another anti-inflammatory drug that can be prescribed is colchicine, a highly poisonous alkaloid when taken in large amounts. Colchicine binds with the protein tubulin, a major component of microtubules, and inhibits cell division. Colchicine also inhibits the actions of neutrophils. Both properties lead to its anti-inflammatory effect. Side effects of colchicine include nausea, vomiting and diarrhea.
While NSAIDs, corticolsteroids and colchicine can quickly eliminate the symptoms of an acute gout attack, doctors prescribe medication that will lower the uric acid level in the body to control and reduce future attacks. Probenecid (Benemid®, Probalan®) and sulfinpyrazone (Anturane®) are drugs that aid the kidneys in excreting uric acid. The drug that is most commonly prescribed to control uric acid levels in the blood is allopurinol (Lopurin®, Zyloprim®), which prevents the production of uric acid by inhibiting the enzyme xanthine oxidase, an enzyme used in the creation of uric acid.
With every patient, the treatment will vary. Medication will vary depending upon the patient’s kidney function and other physical factors. Dietary changes should be made to reduce the intake of purine rich foods as well as reducing or stopping the consumption of alcohol.
Preventing Gout:
In addition to dietary adjustments, gout can be prevented by continuous intake of allopurinol. Gradual weight loss can also make gout easier to manage. Gout can occur subsequently with hypertension, so by treating it with high blood pressure medication such as Losartan may help reducing the uric acid level in the body. The body should also stay hydrated so adequate fluid intake is crucial in managing gout.
Interesting Facts about Gout:
š Cherries, strawberries, blueberries and other dark berries have shown to be able to lower uric acid levels in the blood.
š Gout is sometimes referred to as the “disease of kings” because the rich and powerful are the ones who are often affected by the disease. In reality, it was really caused by their overindulgence of food and wine.
š Famous people who have suffered gout include: King Henry VIII, Nostradamus, Isaac Newton, Alfred Lord Tennyson, Thomas Jefferson and Benjamin Franklin.
Any edits/suggestions/corrections are greatly appreacited. ^_^
--mandy
