Purine and urate metabolism
Martin Andrew Crook in Clinical Biochemistry & Metabolic Medicine, 2013
Abnormalities of purine metabolism are often found in clinical practice, notably hyperuricaemia and gout. Urate is the end product of purine metabolism in humans. Purines synthesized in the body, those derived from the diet and those liberated by endogenous catabolism of nucleic acids may be oxidized to urate or reused for nucleic acid synthesis. Urate is filtered through the glomeruli and most is reabsorbed in the proximal tubules. Renal secretion may be enhanced by uricosuric drugs, which block tubular urate reabsorption. Urate is poorly soluble in plasma. At plasma pH, most urate is ionized at position 8 of the purine ring. In acute attacks of gouty arthritis, local factors are more important than the plasma urate concentration, which is usually normal during the attack. Plasma urate concentrations are low in children and rise in both sexes at puberty, more so in males than in females; concentrations are highe.
Lesch–Nyhan disease and variants
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Male infants with the P. Lesch–W. L. Nyhan disease appear normal at birth and usually develop normally for the first six to eight months. In variants, hyperuricemia, gout, or renal calculi; in a neurologic variant, the phenotype is identical to that of Lesch–Nyhan disease, but self-mutilation is absent and intelligence may be normal; in another variant, the expression is of dystonia mimicking spastic diplegia and mildly impaired mental development. Lesch–Nyhan patients do not have sensory abnormalities; they scream in pain when they bite themselves and cry in terror of its anticipation. The discovery of the enzyme defect in Lesch–Nyhan disease was followed shortly by the recognition of deficiency of the enzyme in patients with gout or urinary tract calculi. In contrast to the mutations in the classic Lesch–Nyhan disease, the majority of the variants had missense mutations.
Crystal deposition disorders
Ashley W. Blom, David Warwick, Michael R. Whitehouse in Apley and Solomon’s System of Orthopaedics and Trauma, 2017
Crystal deposition diseases are common although most are managed in primary care or by medical intervention. Gout is a crystal deposition disease caused by deposition of monosodium urate crystals in joints and other tissues, secondary to hyperuricaemia. Gout is associated with a number of comorbidities including metabolic syndrome , cardiovascular disease , hypertension and diabetes . Acute gout can only be diagnosed with certainty by identifying urate crystals in synovial fluid, bursa or aspirate of tophus. Anti-inflammatory agents are the drug of choice for the treatment of acute gout without comorbid diseases. Basic calcium phosphate (BCP) crystal deposition disease may occur in and around joints as a result of local tissue damage – strained or torn ligaments, tendon attrition and cartilage damage or degeneration. A destructive form of osteoarthritis (OA) affecting the shoulder or hip has been described in elderly individuals, associated with rotator cuff defects and aggregates of BCP in the fluid.
The management of hyperuricemia with urate deposition
Published in Current Medical Research and Opinion, 2015
G. Desideri, J.G. Puig, P. Richette
Recent epidemiological data suggest a progressive increase of serum levels of uric acid worldwide. This rise in the prevalence of hyperuricemia may be related to the epidemic diffusion of overweight and obesity as well as the shifts in diet with increased consumption of foods rich in purines, alcoholic consumption, and soft drinks sweetened with fructose. The rise in serum uric acid levels worldwide may be regarded as leading an increased risk for gout and other systemic diseases, especially in the cardio-renal system. Therefore, careful management of hyperuricemia with urate deposition is crucial to prevent or even treat those systemic diseases. Despite this, hyperuricemia and gout often remain untreated. This paper reviews current evidence on the management of hyperuricemia with urate deposition, with a focus on its most controversial aspects. This review is based on a PubMed/Embase database search for articles on hyperuricemia and its impact on cardiovascular and renal function.
Hyperuricemia, urate deposition and the association with hypertension
Published in Current Medical Research and Opinion, 2015
G. Mancia, G. Grassi, C. Borghi
Hyperuricemia is associated with hypertension, kidney disease, vascular and cardiovascular (CV) events. In experimental models, the inhibition of hepatic uricase induces hyperuricemia, hypertension and mild renal disease. Notably, the micro- and macrovascular changes observed in the experimental model of hyperuricemia resemble the histological changes of human hypertension. This paper presents and discusses the epidemiological correlation between high serum uric acid levels and hypertension, and reviews current evidence supporting the protective effects of the normalization of uric acid levels. This review is based on a PubMed/Embase database search for articles on hyperuricemia and its impact on cardiovascular and renal function.
Association of hyperuricemia and pulmonary hypertension: A systematic review and meta-analysis
Published in Modern Rheumatology, 2019
Tae Uk Kang, Kyu Yong Park, Hyun Jung Kim, Hyeong Sik Ahn, Shin-Young Yim, Jae-Bum Jun
Objectives: To investigate the association of hyperuricemia with pulmonary hypertension (PH) in term of subsequent development, severity, and prognosis of PH. Methods: The authors systematically reviewed articles from databases and conducted meta-analyses as follows: (1) association of serum uric acid (UA) levels with the presence of PH; (2) association between serum UA levels and subsequent development of PH, in terms of odds ratio of the development of PH; and (3) association of serum UA levels with severity and prognosis of PH, in terms of pulmonary arterial pressure and hazard ratio of death. Results: Twenty-six studies published between 1999 and 2017 were included. The level of serum UA was higher in subjects with PH than subjects without PH and this finding was observed regardless of status of diuretics use or renal function. The odds ratio of the development of PH was 2.32 (95% CI, 1.05–5.15) in subjects with hyperuricemia. Pulmonary arterial pressure among subjects with PH was also higher in subjects with hyperuricemia than subjects with normouricemia. There was a 19% increased hazard ratio of death (95% CI, 1.06–1.33) among patients with PH who had hyperuricemia. Conclusion: Hyperuricemia is associated with the subsequent development, worse severity and poor prognosis of PH.
Related Knowledge Centers
- Pathologic Processes
- Uric Acid
- Hypertension
- Blood
- Gout
- Nyhan Syndrome
- Lesch