Search

Theoretical consideration of the crystal lattice dimensions of calcium oxalate monohydrate (COM) and those of uric acid (UA) shows that there are dimensionally closely matched crystal surfaces and suggests that epitaxial growth can take place between these two common kidney stone components. In vitro demonstration of epitaxial growth of COM crystallites on well developed (100) faces of UA crystals has added support to the theory. Another study has shown that monosodium urate (MSU) is a better heterogeneous nucleator for COM, but MSU crystals are rarely observed in kidney stones. The important question of whether or not epitaxial growth of COM on UA or vice versa actually takes place in vivo has not been answered. Obviously, a direct observation in situ is not practical. Indirectly, we can look carefully at the end products — mixed kidney stones containing UA and COM or calcium oxalate dihydrate (COD), for clues of such an event.

In order for acute gouty arthritis to occur, neutrophils must interact with monosodium urate (MSU) crystals. As a result of this interaction, enzymes, chemotactic factors, and other mediators of the inflammatory response are released from neutrophil lysosomes [1]. We have observed previously that MSU crystals adsorb gamma globulin, albumin, and other proteins found in serum and joint fluid [2]. This study was designed to demonstrate the effects of coating of MSU crystals with proteins on the phlogistic responses of neutrophils to crystals.

Monosodium urate deposits almost exclusively in the connective tissue of patients with gout. Thereby the question arises why the connective tissue is the predilective locus for monosodium urate. Several theories about the localised deposition of monosodium urate crystals in connective tissue demonstrate the interaction of urate with the components of the connective tissue.

Although the etiologic role of microcrystalline monosodium urate monohydrate in the pathogenesis of acute gouty arthritis has been well established, the mechanism by which urate precipitates in joints, soft tissues and the kidneys remains unclear. Some studies have suggested that the solubility of urate is the key factor and that when the solubility of urate in blood synovial fluid and urine is exceeded, urate then precipitates. The question is more complex than this, however, since only approximately 25 per cent of patients with hyperuricemia develop acute gouty arthritis. Furthermore, there is poor correlation between uric acid concentration and the frequency of acute gouty attacks. This has led to speculation that there are factors in serum which are partially responsible for solubilization of urate and that alterations in these factors could be responsible for urate deposition.

The aim of this study was to assess the role of dietary sodium on lithogenic ion excretion and its effect on urinary saturation/inhibition indexes.

The relationship between uric acid and the human kidney is a topic of perennial interest (1). The kidneys, although responsible for the major component of urate elimination, can also be affected adversely by uric acid and its monosodium salt. In this chapter, we shall sketch the different types of renal involvement caused by uric acid or urate, and review the therapeutic modalities which are available.

For the sake of argument, I’ve decided to build this talk around the base of the great toe. We now accept the idea that acute gouty arthritis has a physical cause: the sodium urate monohydrate crystal. We can logically extend that concept, then, to say that there must be a physical reason or reasons why one joint receives such a disproportionate share of these crystals and of the miseries they inflict. Ideally, that same reason should explain why attacks are provoked by exertion, why they occur in the middle of the night and why gout usually strikes patients in their forties when hyperuricemia may have been present since puberty.

The demonstration of urate crystals in synovial fluid and within synovial leukocytes is recognized as the most definitive criterion for the diagnosis of gout (1). The characteristic crystals have been described by scientists from Van Leeuwenhoek in the 1600’s to the present as being “needle-like” in shape. These crystals have been further described by their anisotropic quality of birefringence detectable by using the polarizing microscope. Addition of a first order red quartz conpensator to the optic system helps identify monosodium urate monohydrate (MSUM) by its ability to alter the light’s wavelength and change the transmitted color from red to yellow in the gamma plane of the compensator (2). MSUM is thus, by definition, negatively birefringent. Crystals which are blue when parallel to the gamma plane are defined as positively birefringent.

Monosodium urate (MSU) crystals play a crucial role in the pathogenesis of gouty arthritis. MSU have been shown to be phagocytosed by polymorphonucelar cells, chondrocytes and synovial cells resulting in the release of prostaglandins and proteolytic enzymes (1).

Gouty arthritis with or without tophaceous deposits and uric acid nephrolithiasis are the clinical manifestations of hyperuricemia known collectively as the gouty diathesis. While the pathogenesis of hyperuricemia may involve either a primary (genetic) or secondary abnormality of uric acid metabolism, the incidence and severity of the clinical manifestations have been related to two other factors, the magnitude and the duration of hyperuricemia1 However, recent investigations into the pathogenesis of gouty arthritis have demonstrated that both soluble and cellular mediators of the inflammatory process are important in the pathogenesis of the articular inflammation associated with monosodium urate (MSU) crystals2. The relationship of these factors to those previously shown to be of importance in the pathogenesis of gouty arthritis has not been clarified. However, they introduce new variables which potentially are of significance in determining the eventual clinical manifestations of hyperuricemia. This report concerns an 83 year-old patient who noted the gradual appearance of multiple tophaceous deposits over a period of at least 20 years, yet had never experienced an attack of gouty arthritis.

The membranolytic effects of microcrystalline monosodium urate (MSU) on biologic membranes are well documented for a number of cells and subcellular structures [1–3]. This process has been ascribed to hydrogen-bond formation between the crystal and membrane phospholipids and is blocked by strong hydrogen acceptors such as proteins or anionic polymers [1]. Since the acute inflammatory response of gouty arthritis occurs in protein-rich joint fluid, we have examined the protein adsorptive properties of MSU crystals. The effects of adsorbed protein on polymorphonuclear leukocytes and platelet degranulation were studied and are reported in detai1.