Gout and Hyperuricemia - Essay Example

Gout and Hyperuricemia Four Clinical Manifestations of Hyperuricemia Some of the symptoms associated with hyperuricemia include: 1. Under excretion or overproduction of uric acid; here are high levels of urate in the plasma and connective tissue. 2. Chronic crystal deposition. This leads to swollen, warm, and painful joints. 3. Gout that manifests as acute monoarthritis. The most common one occurs in the big toe. Some patients may develop tophi in the helix of the ear, olecranon bursa or along the surface of the ulna. 4. Uric acid nephrolithiasis which is likely to manifest with heturia, pain in the abdominal region, flank and nausea in some cases (Ronco and Rogeghiero, 2005, p. 27). Pathophysiology of Gout and Hyperuricemia Gout and hyperuricemia is characterized by the excess accumulation of uric acid as a result of its overproduction or underexcretion or both (Wyngaarden and Kelley, 1976, p.46). In the case of overproduction of uric acid, the purines from diet, tissue nucleic acid conversion to purine nucleotides and the de novo synthesis of purine bases get into a common metabolic pathway which leads to the production of uric acid or 2nucleicacid. Any abnormalities in the regulation of purine metabolism may cause the overproduction of uric acid (p. 47). The acid may be overproduced as a result of myeloproliferative and lymphoproliferative disorders and breakdown of tissue nucleic acids. Overproduction of uric acid leads to increased phosphoribosyl pyrophosphate (PRPP) synthetase activity and deficiency of hypoxanthine‐guanine phosphoribosyl transferase (HGPRT ), which is responsible for the conversion of hypoxanthine to ionsinic acid and guanine to guanylic acid. A deficiency of HGPRT is likely to cause hyperuricemia in healthy individuals (p.49). Uric acid elimination occurs in two ways: through urine (66%) and through the gastrointestinal tract. A decline in the level of uric acid urinary excretion results in an increase in sodium urate pool and hyperurecemia. Accumulation of uric acid in the urine is determined by glomerular filtration, tubular reabsorption, tubular secretion, and postsecretory reabsorption. Enhanced sodium reabsorption also means increased reabsorption of uric acid. Any factor that increases the production of uric acid and decreases its clearance results in elevated levels of serum urate concentration, causing gout and hyperuricemia (Teng, Nair and Saag, 2006, p. 1549) Clinical Presentation of the Various Forms Of Gout 1. Acute gouty arthritis Acute gouty arthritis is characterized by the rapid onset of swelling, inflammation and excruciating pain in affected joints. The attack is normally monoarticular at the beginning and it affects the first metatarsophalangeal joint and then spreads to the insteps, ankles, heels, knees, wrists, fingers, and elbows. It is likely that the predilection of low extreme acute gout in peripheral joints is related to the high intraarticular urate concentration and low temperature of joints (Terkeltaub and Edwards, 2010, p.18). There are synovial effusions which are assumed to occur momentarily in the weight bearing bones in the course of a normal day. At night there is reabsorption of water in the joint space, resulting in an oversaturated solution of monosodium urate, which often leads to acute arthritis attacks. These attacks are characterized by sudden excruciating pains. The crystal induced inflammation is caused by chemical mediators that cause vasodilation, increased vascular permeability and chemotactic activity for polymorphonuclear leukocytes. Urate crystals phagocytosis by the leucocytes causes rapid cell lysis and a release of proteolytic enzymes into the cytoplasm. Inflammation ensues, and it comes with intense pain on the joints, warmth, erythma and swelling (Ronco and Rogeghiero, 2005, p. 40). Acute gouty arthritis attacks may happen without being provoked. However there are some conditions that might precipitate an attack. These conditions include: trauma, stress, infection, alcohol ingestion, surgery, ingestion of uric acid lowering agents, taking drugs that can elevate serum acid concentrations. Diagnosis of acute gouty arthritis is by aspiration of synovial fluid, which is from the affected joint and the identification of monosodium urate intracellular crystals in synovial fluid leukocytes (Terkeltaub and Edwards, 2010, p. 24). 2. Uric Acid Nephrolithiasis Uric acid nephrolithiasis is normally caused by excessive uric acid urinary excretion, acidic urine and highly concentrated urine (more than 1100 mg/d). The pH of uric acid is pKa of 5.5. Therefore, when the urine is acidic, uric acid exists primarily in the less soluble un‐ionized form. At a urine pH of 5.0, urine is saturated at 15 mg/dL of uric acid level. In patients who have nephrolithiasis, urinary pH is normally less than 6.0 and often less than 5.5. When acidic urine has high levels of uric acid, unprompted precipitation of stones may happen (Terkeltaub and Edwards, 2010, p. 26). 3. Gouty Nephropathy There are two forms of gouty nephropathy: acute uric acid nephropathy and chronic urate nephropathy. In acute uric acid nephropathy there is acute renal failure which occurs as a result of urine flow being blocked. This results to the intense precipitation of uric acid crystals in the ureters and collecting ducts. Patients who have myeloproliferative or lymphoproliferative disorders normally have this form of gouty nephropathy. The accumulation of urate crystals in the renal parenchyma is what causes chronic urate nephropathy. In this case, microtophi may form, resulting in a cell inflammatory reaction. Characteristics of this condition include: the kidney’s decreased ability to concentrate urine, proteinuria, hypertension and nephrosclerosis (Terkeltaub and Edwards, 2010, p. 28). 4. Tophaceous Gout Tophi (urate deposits) are a late complication of hyperuricemia. Tophi may cause deformities, damage surrounding soft tissue, cause joint destruction and pain, and can also lead to nerve compression syndromes such as carpal tunnel syndrome (p. 31). Predilection the Anatomic Sites Involved In Acute Gouty Arthritis During the course of the day, Synovial effusions are assumed to occur momentarily in weight‐bearing joints. Water is then reabsorbed from the joint space during the night. This leaves behind solution of a supersaturated solution of monosodium urate which is supersaturated. This can cause acute arthiritis. Attacks for acute arthritis normally start at night (p. 35) Likelihood of Nephrolithiasis in Patients with Hyperuricemia Based On Urinary Ph and Uric Acid Excretion Rates The pKa of uric acid is estimated to be 5.5. This means that when the urine is acidic, uric acid will exist in the un‐ionized form, which is also less soluble. Urine is normally saturated at a uric acid level of 15 mg/dL when it has a pH of 5.0. The solubility of uric acid in 7.0pH urine increases to 200 mg/dL. Patients who have uric acid nephrolithiasis have a urinary pH which is less than 6.0 and in most times, less than 5.5. sponataneous precipitation of stones might occur when acidic urine is saturated with uric acid (Wyngaarden and Kelley, 1976, p.50). Types of Gouty Nephropathy Based On Pathophysiologic Mechanisms The two types of gouty nephropathy are: acute uric acid nephropathy and chronic urate nephropathy. In acute uric acid nephropathy, acute renal failure occurs due to the blockage of urine flow leading to high levels of precipitation of uric acid crystals in the ureters and collecting ducts and. It is a result of immense malignant cell turnover, which normally occurs after chemotherapy. Chronic urate nephropathy comes as a result of accumulation of urate crystals in the renal Parenchyma. This may lead to the formation of Microtophi, surrounded by a giant cell inflammation reaction (Ronco and Rogeghiero, 2005, p. 33). The Most Common Sites of Tophaceous Gout The most common sites of tophaceous deposits are the base of the great toe, knees, and helix of the ear, wrists, olecranon bursae, the Achilles tendon and hands. The hips, shoulders, and spine may be affected at a later stage (Terkeltaub and Edwards, 2010, p. 24). Plan for Treating Acute Gouty Arthritis in a Patient Who Has Been Symptomatic For More Than 48 Hours For a patient who has been experiencing acute gouty arthritis symptoms for more than 48 hours, Indomethacin rather than colchicines is the recommended medication. For the first 24-48 hours, large doses of the medicine may be given. 75mg is a good amount to start with. The doses may be reduced gradually over the next 3 to 4 days to reduce the risk of a recurrent attack. The 75 mg may be reduced to 50 mg for every six hours for a period of two days. This can then be reduced further to 50 mg every eight hours after that. If the inflammation is only on a single joint, the patient may be given 20-40 mg of triamcinolone hexacetonide. However for patients with multiple joint acute gouty arthritis, Prednisone may be given orally in doses of 30-60 mg for 3-5 days. The dose should be decreased gradually by 5 mg over 10-14 days and then eventually discontinued (Ronco and Rogeghiero, 2005, p. 77). A Treatment Plan for Uric Acid Nephrolithiasis The treatment of uric acid nephrolithiasis involves hydration which should be enough to maintain a urinal volume of 2-3 L/d, avoidance of foods rich in purine, urine alkalinization, moderation of protein intake and reduction in the excretion of urinary uric acid. To maintain a urine volume of 2-3 L/d, gouty patients are encouraged to take ample fluids (Teng, Nair and Saag, 2006, p. 1555). Alkalinisation is taken to ensure that acid in the urine is regulated. The pH for urine should be between 6.0 and 6.5 (p. 1556). Gout Patients in Whom Prophylactic Therapy Should Be Implemented Gout patients who should undergo prophylactic therapy are: Those who have had the first acute gouty arthritis attack Those who have just passed their first renal stone Those who have suffered severe attacks of gouty arthritis, complicated uric acid lithiasis, elevated levels of serum uric acid (more than 10.0 mg/dL) or uric acid urinary excretion of more than 1000 mg Those who have had frequent attacks of gouty arthritis ((Wyngaarden and Kelley, 1976, p.67) References Ronco, C. and Rogeghiero, F. (2005). Hyperuricemic syndromes: Pathophysiology and therapy. Unionville, CT: Karger Teng, G.G., Nair, R. and Saag, K.G. (2006). Pathophysiology, clinical presentation and treatment of gout. Drugs, Vol 66, issue 12, pp. 1547 – 1563. Terkeltaub, R and Edwards, L. (2010). Gout: Diagnosis and Management of Gouty Arthritis and Hyperuricemia. New York: Professional Communications Wyngaarden, J.B. and Kelley, W. (1976). 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