Gouty Arthritis Definition Development Causes Symptoms And Treatments Biology Essay

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Gout mostly occur in the presence of hyperuricemia. Hyperuricemia is defined in a way that the level of urate serum concentration exceeds 7.0mg/dL in men and 6.0mg/dL in women. However, the concentration level varies distinctly amongst different communities. It is influenced by age, gender, ethnicity, body weight, and the surface area of the body. Hyperuricemia usually result from either excessive uric acid formation or lackage of uric acid excretions. In certain cases, it is said that hyperuricemia might result from a combination of both.

Primary gout is a genetically heterogeneous disorder caused by inborn metabolic factors that alter the negative feedback of homeostasis, which is an involuntary process done by our body to adjust itself to be at optimum condition.

Genetic and Biochemical Basis of Hyperuricemia

There are 3 different types of rooted defects which lead to initial stage of development of severe hyperuricemia and gout. Namely, glucose-6-phosphatase (gene symbol = G6PT) deficiency; severe and partial hypoxanthine-guanine phosphoribosyltransferase (HGPRT, gene symbol = HPRT) deficiency; and elevated 5'-phosphoribosyl-1'-pyrophosphate synthetase (PRPP synthetase, gene symbol = PRPS) activity.

The main causes of gout was identified over 10 decades ago but the exact genetic causes was only recognised when the modern genetic tools is invented. Gout was only counted as an innate disorder in the seminal work of Archibald E. Garrod in his 1931 publication on inbred errors in metabolism. Garrod considered gout to be a dominantly passed down trait. However, we now know that G6PT deficiencies are inherited as autosomal recessive traits and HPRT and PRPS defects are X-linked traits.

PRPP synthetase is the enzyme responsible for the synthesis of the activated ribose (5'-phosphoribosyl-1'-pyrophosphate, PRPP) necessary for the de novo synthesis of purine and pyrimidine nucleotides. Regulation of PRPP synthesis is effected through complex allosteric regulation of PRPP synthetase. At least three different isoforms of PRPP synthetase have been identified and are encoded by three distinct, yet highly homologous PRPS genes, identified as PRPS1, PRPS2, and PRPS3. The PRPS1 and PRPS2 genes are found on the X chromosome (Xq22-q24 and Xp22.2-p22.3, respectively) and the PRPS3 gene is found on chromosome 7. The PRPS3 gene appears to be expressed exclusively in the testes. All three PRPP synthetase isoforms differ in kinetic and physical characteristics such as isoelectric points (pI), pH optima, activators and inhibitors. Mutations in the PRPS genes that result in superactivity lead to enhanced production of PRPP. Increased levels of PRPP, in turn, drive enhanced de novo synthesis of purine nucleotides in excess of the needs of the body. Thus, the excess purine nucleotides are catabolized resulting in elevated production of uric acid and consequent hyperuricemia and gout.

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an enzyme involved in the salvage of purine nucleotides. HGPRT catalyzes the following two interconversions:

hypoxanthine + PRPP <--> IMP + PPi

guanine + PRPP <--> GMP + PPi

A complete or virtually complete loss of HGPRT activity results in the severe disorder, Lesch-Nyhan syndrome. Although Lesch-Nyhan syndrome is known more for the associated bizarre emotional behaviors, there is also overproduction and excretion of uric acid and gouty manifestation. Less dramatic reductions in HGPRT activity do cause hyperuricemia and gout due to the reduced salvage of hypoxanthine and guanine leading to increased uric acid production.

Deficiencies in glucose-6-phosphatase result in type I glycogen storage disease (von Gierke disease). However, associated with this defect is increased uric acid production and symptoms of gout. The inability to dephosphorylate glucose 6-phosphate leads to an increase in the diversion of this sugar into the pentose phosphate pathway (PPP). One major product of the PPP is ribose 5-phosphate. An increase in the production of ribose 5-phosphate results in substrate-level activation of PRPP synthetase. Increased activity of PRPP synthetase, in this circumstance, has the same consequences as defects in the PRPS gene that lead to superactivity of PRPP synthetase described above.

CAUSES OF GOUTY ARTHRITIS

One of the main causes in gouty arthritis is hyperuricemia, which is excessive upraise of uric acid in blood content resulting in bulding up of urate crystals around the joints. The accumulation of urate crystals around the joints cause inflammation and acute pain when a gout attacks.

Break down of purines is called uric acid. Purines can be easily found in body and food resources. For instance, organ meats, anchovies, asparagus, mushrooms, and herring.

Mostly, uric acid would dissolve and enters the urine through kidneys. But, when the body is producing too much of uric acid, the body cannot compensate thus causing kidneys not able to excrete sufficient uric acid, uric acid would end up building up around joints area. The accumulation looks like sharp pointy needles. Therefore, producing throbbing pain, swelling, and inflammation.

To a certain of surprise, the findings said that hyperuricemia is commonly found in people who never develop gout. But there are still some debates going around genetic factor that causes the occurrence of hyperuricemia.

Below are the known causes that bring about a gout attack:

obesity

heavy alcohol consumption, especially beer

a diet high in purine foods, such as seafood and meat, and meat organs

extremely low calorie diets

regular aspirin use

regular niacin use

regular use of diuretic medicines

medicines taken by transplant patients, such as cyclosporine

fast weight loss

chronic kidney disease

hypertension (high blood pressure)

psoriasis

tumors

myeloma

hemolytic anemia

lead poisoning

hypothyroidism

surgery

Kelley-Seegmiller syndrome

Lesch-Nyhan syndrome

SYMPTOMS OF GOUTY ARTHRITIS

Gout's signs and symptoms are acute in general. They come on sudden base without any warning. A great amount of patients experience gout attacks at night.

Severe pain in the joints - The patient may experience pain in his ankles, hands, wrists, knees or feet. More commonly the big toe is affected (podagra). Many patients describe the affected areas as warm/hot. The fluid sacs that cushion tissue (bursae) may become inflamed (bursitis) - when this happens in the elbow it is called olecranon bursitis, while in the knee prepatellar bursitis.

Gradually goes away - A bout can last for over a week if left untreated - and then gradually goes away during the following week or two.

Itchy and peeling skin later - As the gout subsides the skin around the affected area may be itchy and peel. By the end of it the patient feels fine.

Redness and inflammation - The sufferer will most likely have tender, red and swollen joint(s) in the areas that experienced the most pain.

Red/purplish skin - The affected area may become red or purplish, making the patient think he has an infection.

Fever - Some patients have an elevated temperature due to the failure of homeostasis process - negative feedback.

Less flexibility - The affected joint may be harder to use, the patient has limited movement.

No symptoms - Some patients experience no symptoms. In these cases it may develop into chronic gout.

Nodules - The gout may first appear as tophi (nodules) in the elbows, hands, or ears, usually in joint regions.

EXAMS AND TESTS FOR GOUTY ARTHRITIS

Diagnosis:

The first step to diagnose is to determine which part of the joints are affected. A series of physical and subjective examination can be carried out to make certain of gouty arthritis. For example, gouty arthritis usually attacks big toe.

The speed of the onset of pain and swelling is crucial as symptoms take days or weeks to develop. Thus it might indicate other disorder rather than gout attacks.

Sudden enlargement in joints that were caused by previous injuries or osteoarthritis are possible signs of gout. Older women who consume diuretics "water pills" might have a higher tendency.

Blood Test for Uric Acid Levels:

Commonly, a blood test is done in order to measure the levels of uric acid in blood to detect the percentage of hyperuricemia. Low level of uric acid in blood is slightly impossible for gout attacks whereas a very high level of uric acid depicts the likelihood of gout, accompanied by symptoms of gout on patient. However the level of uric acid contain either at the normal range or below does not brings the idea of someone has gout. Even if one has hyperuricemia would not be necessarily being attacked by gout.

Examination of Synovial Fluid:

Upon diagnosing gout, the most accurate method is believed to be synovial fluid examination as synovial fluid is the lubricating liquid that fills up the synovium (a membrane that surrounds a joint and creates a protective sac). The fluid covers the joints in a rim form as well as supplies nutrients and oxygen to the cartilaginous surfaces articulating the bones. This form of examination also helps to detect gout during intercritical periods

.

Health care practitioner uses a needle attached to a syringe to draw out fluid from the affected joint. This is called aspiration. Local anesthesia (loss of sensation) is not used because it can reduce the effectiveness of the procedure. However, the procedure is usually only slightly uncomfortable. Afterwards, there can be some minor discomfort in the area where the needle was inserted, but it usually goes away quickly. It is believed to have certain numbness, swelling, and pain that prohibit movements around that region.

The fluid sample is sent to a laboratory for analysis. This test would reveal the presence of monosodium urate (MSU) crystals, which will nearly always confirm a diagnosis of gout. The laboratory can also test the sample for infection.

The procedure itself can cause infection, though this occurs in less than 0.1% of patients. Aspiration sometimes eases the patient's symptoms by reducing swelling and pressure on the tissue surrounding the joint.

Urine Tests:

When the patient is young and is confirmed having high level of uric acid in body due to metabolic disorders, urine test is carried out. If uric acid in the urine exceeds a particular value, further tests for an enzyme defect or other identifiable cause of gout should be performed. Greater-than-normal amounts of uric acid in the urine also mean that the patient is more likely to develop uric acid kidney stones.

Typically, a 24-hour urine test is performed. The patient discards the first urination sample on the day of the test. Afterward all urine passed over the next 24 hours is collected into a special container, including the first urination on the morning of day two. The container is delivered to the patient's health care provider or sent directly to the laboratory.

The urine is collected during an intercritical period, after the patient has been placed on a purine-reduced diet. The patient is also asked to temporarily stop using alcohol and any medications that can interfere with the test. The patient should not change any of his or her usual eating or drinking patterns when performing this test.

Imaging Tests:

X-Rays. For the most part, x-rays do not reveal any problems during the early stages of gout. Their usefulness lies in assessing the progress of the disorder in its chronic phase and identifying other health problems with symptoms similar to gout. Tophi can be seen on x-rays before they become apparent on physical examination.

Advanced Imaging Techniques. Advanced imaging techniques being investigated for identifying tophi include computed tomography (CT), magnetic resonance imaging (MRI), and Doppler ultrasonography.

PHYSIOTHERAPY TREATMENTS FOR GOUTY ARTHRITIS

STRETCH:

Stretching is a vital part of physical therapy for gout patients. In fact it engages in different form of exercises. It helps to increase blood circulation and to reduce stiffness. Stretching is an important part of physical therapy for gout. Stretching involves engaging in different forms of moderate exercise. This helps increase circulation and reduce stiffness. Performing simple stretches, such as knee bends, helps relieve tension in the joints and reduce inflammation. Knee bends are done by leaning over, with a slight bend in your knees, and attempting to touch your toes. Other suggested range of motion exercises are yoga, tai chi and pilates.

STRENGTH:

Strengthening exercises gives great muscle tones and give you strong, healthy joints. Strength exercises for physical therapy programs typically involve using light weights during leg exercises, such as lunges and squats. This promotes circulation in legs and feet, and also prevents joint inflammation.

To do squats, hold a pair of dumbbell weights at your sides, and slowly bend knees until hamstrings are parallel with the ground. Make sure your back is straight. Slowly stand up. Repeat.

For lunges, start in the same manner, but rather than bend down, take a step forward. Keep upper body vertical. Lean front leg forward just until back knee is barely off the ground. Now step back and repeat with other leg.

ENDURANCE:

Endurance programme focuses more on cardiorespiratory challenging exercises to improve blood circulation, heart function, and to relieve symptoms of gout. Because of recurrent attacks of gout at feet, it is at best to engage in low-impact exercises that would not put additional strain on one's lower extremities. Usually activity like swimming, cycling, jogging is highly encouraged. The intensity of programme would be added when one can perform well at a certain level.

CONCLUSION

. To conclude, the attacks of gout is dependent on individuals health condition and daily lifestyle. A person's action justify the body condition. This point is thoroughly supported by the phrase "You Are What You Eat ".

Gouty arthritis could not be cured as it would come again. All one can do is to cultivate good nutrition and healthy lifestyle to prevent and avoid gout attacks from happening again. Though a person have not had gout in a while after the last attacks in previous few years, the possibility is still there.

There are a lot of measures in pain eases of gout, especially medications. Physiotherapists use different method of approaching gout patients. The approaches are usually easily done in a given space and is more practical.

Therefore, start cultivating good nutrition and healthy lifestyle from today onwards and fret not about Gout anymore!

GLOSSARY

Allosteric = Pertaining to an effect on the biological function of a protein,

produced by a compound not directly involved in that function (an

allosteric effector) or to regulation of an enzyme involving

cooperativity between multiple binding sites (allosteric sites).

Autosomal = Relating to any chromosome besides the X and Y sex

chromosomes.

Bizarre = Referring to a strange thing.

Catabolism = The metabolic breakdown of complex molecules into simpler ones,

often resulting in a release of energy.

Cyclosporine = A cyclic oligopeptide immunosuppressant produced by fungus

and used to inhibit organ transplant rejection.

De novo = From the beginning; anew; over again.

Depicts = To represent in words; describe.

Diuretic = A substance or drug that tends to increase the discharge of urine.

Diversion = The act or an instance of diverting or turning aside; deviation.

Hamstrings = Any of the tendons at the rear hollow of the human knee.

Hemolytic anemia = A disorder in which the red blood cells are destroyed

prematurely.

Heterogeneous = Consisting of dissimilar elements or parts; unlike; incongruous.

Homeostasis = The state of balance in the internal environment of the body

achieved by various control mechanisms.

Homologous = Pertaining to corresponding attributes or similar in structure.

Hyperuricemia = Excessively high levels of uric acid in the blood, often producing

gout.

Hypothyroidism = A pathological condition resulting from thyroid insufficiency.

17. Innate = Possessed at birth; inborn; hereditary; congenital.

18. Intercritical = Denoting the period between attacks, as of gout.

19. Kelley-Seegmiller syndrome = Partial HGPRT deficiency that causes

Hyperuricemia and leads to gouty arthritis and the

formation of uric acid stones in the urinary tract.

Lesch-Nyhan syndrome = A familial disorder of uric acid metabolism and central

nervous system dysfunction.

Manifestation = An obvious indication or specific evidence that a disease is

present; a symptom.

Mutation = A permanent change in the genetic material that may alter a trait or

characteristic of an individual, or manifest as disease, and can be

transmitted to offspring.

Myeloma = A tumor that originates in bone marrow and usually spreads to more

than one bone.

Niacin = A crystalline acid that is a component of the vitamin B complex and is

used to treat and prevent pellagra.

Pilates = A series of nonimpact exercises designed by Joseph Pilates to develop

strength, flexibility, balance, and inner awareness.

Psoriasis = A chronic, non-contagious disease characterized by inflamed lesions

covered with silvery-white scabs of dead skin.

Salvage = The rescue and use of any found or discarded material.

Tophi = A chalky deposit of a uric acid compound found in gout.

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