Editing Stones: Epidemiology and Pathogenesis (section)

== Physiochemistry and Pathogenesis ==

* '''<span style="color:#ff0000">Urine must be supersaturated for stones to form; however, supersaturation alone is not sufficient for crystallization to occur in urine due to the presence of urinary inhibitors</span>'''
** The state of saturation of the urine with respect to particular stone-forming salts indicates the stone-forming propensity of the urine. The state of saturation is determined by pH and the ionic strength of the major ions in solution.
** The solubility product refers to the point of saturation where dissolved and crystalline components in solution are in equilibrium. Addition of more crystals to the solution will result in precipitation of crystals. In this supersaturated urine (metastable state), crystallization can occur on preexisting crystals, but spontaneous crystallization occurs only when the concentration product exceeds the formation product. In the supersaturated state, the presence of inhibitors prevents or delays crystallization.
*** The process by which nuclei form in pure solutions is called homogeneous nucleation.
*** Heterogeneous nucleation occurs when microscopic impurities or other constituents in the urine promote nucleation by providing a surface on which the crystal components can grow.
** '''<span style="color:#ff0000">Known inhibitors of calcium oxalate and calcium phosphate crystallization (6) </span><span style="color:#0000ff">No More Bad Colicky Torturous Urolithiasis:</span>'''
**# '''<span style="color:#0000ff">N</span><span style="color:#ff0000">ephrocalcin</span>'''
**# '''<span style="color:#0000ff">M</span><span style="color:#ff0000">agnesium</span>'''
**#* Inhibitory activity derived from its complexation with oxalate, which reduces ionic oxalate concentration and calcium oxalate supersaturation
**# '''<span style="color:#0000ff">B</span><span style="color:#ff0000">ikunin</span>'''
**# '''<span style="color:#0000ff">C</span><span style="color:#ff0000">itrate</span>'''
**#* '''<span style="color:#ff0000">Most important factor</span>'''
**#* '''MOA (4):'''
**#*# '''Complexes calcium''', thereby lowering urinary saturation of calcium oxalate
**#*# Inhibits spontaneous precipitation of calcium oxalate and agglomeration of calcium oxalate crystals
**#*# Inhibits calcium oxalate and calcium phosphate crystal growth, with effect on calcium phosphate crystal growth more pronounced than on calcium oxalate crystal growth
**#*# Prevents heterogeneous nucleation of calcium oxalate by monosodium urate
**# '''<span style="color:#0000ff">T</span><span style="color:#ff0000">amm-Horsfall mucoprotein</span>'''
**#* '''Most abundant protein in the urine'''
**# '''<span style="color:#0000ff">U</span><span style="color:#ff0000">ropontin</span>'''
** '''No known inhibitors affect uric acid crystallization'''
* '''<span style="color:#ff0000">Renal calculi consist of 2 components: crystalline and non-crystalline (matrix) components</span>'''
** '''<span style="color:#ff0000">Crystalline</span>'''
*** '''<span style="color:#ff0000">Calcium is the most common component of urinary calculi</span>'''
** '''<span style="color:#ff0000">Non-crystalline (matrix)</span>'''
*** '''Typically accounts for 2.5% of the weight of the stone.'''
*** '''<span style="color:#ff0000">Matrix is a heterogenous mixture consisting of ≈65% protein.</span>''' '''Other components include mucoproteins, carbohydrates, and urinary inhibitor'''
* '''<span style="color:#ff0000">In idiopathic calcium oxalate stone formers, Randall plaques, which are composed of calcium apatite, have been found to originate in the basement membrane of the thin loops of Henle.</span> From there, they extend through the medullary interstitium to a subepithelial location, where they serve as an anchoring site for calcium oxalate stone formation.'''