Amerkan Mincraloght, Volume 59, pages I177-1182, 1974

DescriptiveHuman Pathological Mineralogy

Rrcneno I. Gmsox P.O. Box I O79, Dauis,C alilornia 95 6 I 6

Absfract

Crystallographic, petrographic, and X-ray powder difiraction analysis of approximately 15,000 samples showed that the most common mineral constituents of human pathological concretions are calcium oxalates (whewellite and weddellite), calcium phosphates (apatite, brushite, and whitlockite), and magnesium phosphates (struvite and newberyite). Less are monetite, hannayite, calcite, aragonite, vaterite, halite, gypsum, and hexahydrite."o-rnon of the variables determining which minerals precipitate, the effects of different pH values on deposi- tional conditions are most apparent, and are shown by occurrences and relationships among many of the minerals studied. A pH-sensitive series has been identified among magnesium phosphatesin concretions.

Introduction The study was carried out over a period of three The importanceof mineralogyin the field of medi- years.Composition was confirmedby X-ray powder cine lies in the applicationof mineralogicalmethods diffraction and polarizing microscopy;sequence was to study pathologicalmineral depositsin the human arrived at from considerationsof microscopic tex- body. Urology benefitsgreatly becauseconcretions tural and crystallographicrelationships. More than of mineral matter (calculi) are common in the 14,500samples were derivedfrom the urinary sys- urinary system.The value of mineralogicalanalysis tem of kidneys,ureters, bladder, and urethra; the of urinary material was first describedby prien and remaining samples are not statistically significant Frondel (1947). Mineralogistsmay be unawareof and arediscussed only briefly. the variability and nature of such compounds be- Calcium cause reports are usually published in medical Oxalates journals. This investigationreports the mineralogy Whewellite, CaCzOE.H2O,and weddellite, CaCz- and possiblepathological significanceof these min- O4'2H2O,are very uncommonin the mineralworld. erals. However, they both occur abundantly in calculi. Some mineralogistswould not consider these Although the two phasesare frequentlyassociated materialsminerals in the strictest sense.Because in the samecalculus, their habits are markedlydif- most of thesecompounds are identical with minerals ferentand warrant separate discussion. in compositionand structure,and often in mechanics of their formation, they are herein referred to by Whewellite mineral names,leaving the questionof their status The predominant habit consistsof smooth to unanswered.Only those compoundsexisting else- botryoidal or globular, radiating crystallineaggre- where as minerals, sensu strictu, are discussedin gates.Discrete crystals are rarely present, although detail, even though crystallineorganic compounds a monoclinic(010) or (110) cleavagecan be ob- suchas uric acidand cystineoccur as urinarycalculi. servedin the crystallinemass. The most common colors are brown to olive green, but shadesfrom Scopeand Methods black to yellow exist. This variation is due to dif- The writer determined mineralogic composition fering amountsof includedorganic material, includ- and depositionalsequence for approximately15,000 ing blood. Whewellite calculi very often are de- human pathological mineral depositsobtained from positedupon renal papillae,small protrusions within doctorsand hospitalsin variousparts of the United the kidney. When this happens,the calculusalmost States,with most samplescoming from the Midwest. invariably has a relatively small nucleuswhich is lt77 tL78 RICHARD I. GIBSON usuallycomposed of apatite,brushite, or whitlockite. Calcium PhosPhates Non-papillary whewellite stonesalso may contain a Apatite central apatitecore. Both types of stonesare con- The most important mineral in the human body cenlricallylaminated and radial about the nucleus is apatite, the principal mineral constituent of bones or core, clearly indicating deposition thereon. A and teeth. In urinary calculi two varieties occur: specialkind of whewellitestone is referred to by hydroxyl-apatite,Calo(PO1)6(OH)2, and carbonate- urologists as the jackstone, a calculus with sym- apatite, in which CO3OH groups replace POr in metrical,elongate, branching protrusions. This pref- amounts up to 5 percent by weight. Carbonate- erentialgrowth upon selectedsites on the surfaceof apatite is more abundant in calculi than is hydroxyl- a crystallineaggregate is dueto growthimperfections apatite, but their habits are the same and both are which resultfrom unusualaccumulations of organic labeled in what follows as "apatite." material.Centers of such branchesoften show sub- Apatite is the most widespread mineral in calculi. sidiarynuclei of carbonaceousorganic matter. It is associatedwith most other stone-forming ma- terials, often serving as a center for deposition of Weddellite subsequent compounds. The first of two important In contrastto whewellite,weddellite almost always habits for urinary apatite is soft, crumbly, fine- occursas well-formed tetragonal dipyramidal crystals grained, white, yellow, or light brown powder. The and aggregatesof intergrown single crystals.Colors second habit is massive, glassy, yellow, brown, or are also variable,ranging from the common yellow black material. Again, colors other than white are to white or colorless,again reflectingdifferences in the result of inclusion of organic matter. Both the amount of included organic material. Cycles of powdery and glassy varieties are so fine-grained that growth of weddellite crystals are preservedin the they appear optically isotropic. Apatite is usually crystallinerecord; secondaryand tertiary crops of thinly laminated, both in pure apatite calculi and smaller,differently-colored crystals may be deposited when it occurs as small patches within other mineral upon the facesof early-formedcrystals up to 5 mm frameworks, as in intersticesof intergrown weddellite on an edge.Occasional super-deposition of whewel- crystals. Glassy apatite sometimes consists of con- lite spherulestakes place on the apicesof weddellite centric laminations 2-4 microns thick, especially in crystals,in the tetragonalprism position.However, the rare variety referred to by urologists as "milk of most specimensshow weddellitefollowing wi'rewellite calcium," an unconsolidatedmass of spherical stones in depositionalsequence. The tetragonaldipyramid each less than 1 mm in diameter. Laminations of r {011} is almostunique in weddellite;about 0.5 this material occur on spherulites about one micron percent of calculi containing weddellite display across, which give uniaxial optic figures without the tetragonalprisms a {010}, alwayson yellowcrystals, aid of condensersor a Bertrand lens' and up to 2 mm across.Much smaller tetragonal More common apatite calculi show alternating prisms were also reportedon weddelliteby Hutton layers of the powdery and glassyvarieties. Prien and andTaft ( 1965). Frondel (1947) believed that the glassy laminae condensation of the substance-" While Pseudomorphism "represent a it is possible that surficial powdery apatite could Whewellitecan form by the partial dehydrationof have "condensed" by partial dehydration, dehy- weddellite,resulting in strikingly perfect pseudo- droxy'lation, or even decarbonation, the writer feels morphs.This whewelliteoccurs as finely granularto that mucus and other organic material adsorbed on coarse,equant prisms. Colorless, yellow, green,and the stones' surfaces produce this change in habit. brown varietiesexist, sometimeswithin the same This idea is supported by the action of organic mat- pseudomorph.The replacementof weddellitecrys- ter as a strong pigmenting agent in most stone min- tals beginsat the centerand works outward,becom- erals, and by the fact that light encrustations of ing increasinglyfine-grained. The surfacesof crystals mucus are normally found on the surfaces of many are rarely replaced,probably becausecontact with calculi. the aqueousenvironment of the urinary systemmain- tains the stabilityof weddellite.However, weddellite Brushite calculi kept in dry samplecontainers for over five Isostructural with gypsum, brushite, CaHPOe' yearsshow no tendencyto dehydrateto whewellite. 2H2O, is much less common than apatite in calculi, DESCRIPTIVE HUMAN PATHOLOGICAL MINERALOGY 1179 but still occursregularly. When it doesprecipitate, it is suggestingrelatively long-term changesin the en- a responseto acidicconditions. Beck (personalcom- vironment such as Mg-enrichment.Finally, pure munication) has synthesizedbrushite at pH values whitlockiteis almostthe only constituentof prostatic of 6.3-6.0. Flat, bladed, colorless-to-yellowmono- calculi,and prostaticfluid hasthe highestconcentra- clinic crystalsoccur in calculias radiating aggregates, tion of zinc in the human body. giving the surfacesof stonesa rough, nodular tex- Urinary and prostaticwhitlockite has a distinctly ture. Individual crystals of urinary brushite are resinousluster and a textbook-typehackly fracture. tabularon (010), with {001} and {100} alsousu- Translucentbrown, amber,and yellow laminas are ally present.Small second-orderprisms have been very convolutein section,often clearlyillustrating a noted occasionally.Internally, silky fibers display tendencyfor small stonesto fuse into larger ones. pearlyluster on the perfect (010) cleavage.In four Whitlockiteis the only mineraldiscussed here which instancesbrushite was observedin a partial pseudo- regularlyshows such fusion. In addition,whitlockite morphicreplacement of laminated,powdery apatite. in calculi sometimeshas COgOH replacementof These calculi also containedlater depositsof uric POa, as in apatite. acid, so a changeto a more acid-stablephosphate might be expected.However, uric acid and apatite Maglesium Phosphates coexistin manycalculi. Magnesiumphosphates are important indicators of infectionsin the urinary system.In many cases, Monetite the precipitationof the mineralsthemselves may be This triclinic, anhydrousanalog of brushitewas enhancedor catalyzedby the presenceof the infec- identifiedonly three times in this group of calculi. tive organisms.The three urinary magnesiumphos- Prien and Frondel (1947) reported it in urinary phates describedhere form a pH-sensitiveseries sedimentsof carnivorousanimals. Beck, Mulvaney, which is sometimesuseful in clinical treatmentof and Rhamy (1974) studiedthe first reportedhuman calculi;however, buffering and stabilizingeffects of o,ccurrences,attributing its formation to very low infectiveorganisms are poorly understood. urinarypH (4.13-5.08), naturallybuffered urines, and high osmolality. Monetite in the calculi ex- Struuite aminedby the writer waslaminated, gray-to-brown, Struvite, MgNH+PO+.6H2O, is orthorhombic- finely granularmaterial associated with oxalatesand pyramidalin crystallization.This hemimorphicsym- apatite.Beck's monetite calculi also displayedlath- metry is best shownby well-formed,colorless crys- like triclinic crystals,and an additional associate tals larger than 1 mm across,which displaya wide wasbrushite. variety of forms. Such crystalsline cavities,cracks, and pore spacesin laminatedstones composed of Whitlockile powdery apatite co-precipitatedwith small, white, Caa(POr)zhas long beentenned whitlockite,but rounded to blocky struvite crystals.These calculi with recentredefinition of the mineral its formula is often developirregular brancheswhich reach into now given as ca CasMg(PO+)u.The X-ray pattern creviceswithin the kidney; they are called "stag- of the urinarycompound matches that of whitlockite, horns" by urologistsand almost always are asso- but adequatechemical analyses are lacking to con- ciatedwith urea-splittinginfections caused by several firm the presenceof magnesiumin the urinary ma- strainsof bacteria.The proportionsof apatite and terial. The following discussion is appropriate struvite in staghorncalculi vary from Ape to Aproo, whetheror not the urinary compoundcontains es- but most are in the range Ap76 to Apr". With in- sentialmagnesium. creasingstruvite content,stones become more po- Whitlockite is unstable in the urinary system; rous, and aggregatesof struvite crystalsassume a apatite should precipitateinstead. However, whit- columnar,slightly radial arrangement.This change lockite is stabilizedin nature by small amountsof of habit probablyreflects the strongeffect of centers magnesiumand zinc, and this almostcertainly hap of nucleationon modeof crystallization,as alsoseen pensin the human body as well. Small amountsof in the radial habits of whewellite,brushite, han- whitlockite sometimes encrust stones containing nayite,and someother stoneconstituents. Although struvite, a magnesiumphosphate, and when asso- apatiteand struviteare usuallyintimately co-precipi- ciated with apatite,whitlockite forms thick layers, tatedin humanstones, occasional calculi show alter- l 180 RICHARD I. GIBSON nating layers of pure apatite and pure, glassy,densely The association of this acid phase with struvite intergrown struvite crystals. and ammonia-producing bacteria might be explained The infected urines which precipitate struvite are by some biologic activity as yet not understood. Per- also alkaline. This accounts for the presenceof am- haps groups of individual bacteria create an acidic monium in this compound, and for its rare associa- micro-environment while catalyzing the ammonia- tion with oxalates, acid calcium phosphates,and uric producing reaction. Precipitation of newberyite acid, all of which are stable in more acidic, sterile spherulesmight begin in such a micro-environment. urines. Struvite is clearly the alkaline end member of Hannayite the magnesiumphosphate pH seriesin calculi. Noted five times in this seriesof calculi, hannayite, Newberyite Mga(NH+)sHa(PO+)+'8H2O, is a triclinic mineral A mineralogic enigma is presented by newberyite, occurring as soft, white, sheaf-like laths and radial an acid phosphate(MgHPO+'3HrO) which is none- sprays. In four cases it encrusts calculi in loose theless frequently associatedwith struvite and with crystalline aggregates; in the fifth it constitutes infections of Proteus mirabilis, bacteria known to denser,probably initial depositsof intergrown sheafs liberate NH3 and thus increase pH by their activity radiating from many centers. Associated minerals in the urinary system (M. J. Sullivan and R. K. are apatite and struvite (3 cases); apatite, struvite, Rhamy, personal communications). However, new- and newberyite (1 case); and apatite, whewellite. beryite is found in calculi in two distinct habits, and weddellite (1 case). The formula and varied which may reflect precipitation resulting from bac- association of hannayite suggestthat it represents a terial activity as well as precipitation under true response to near-neutral conditions in the urinary acidic conditions. system. Molecular ratios with respect to magnesium The most common occurrence of newberyite is as indicate that slightly acidic conditions would be pale-green-to-white,textured spherules scattered on favored. Its rarity is probably causedby the difficulty the surfaces and in pore spaces of apatite-struvite of maintaining a delicate pH balance in the human stones, Many calculi containing this type of new- body over significantlengths of time. beryite are crumbly and fragmented, with spherules Miscellaneous UrinarY Minerals occurring on broken inner surfaces as well as on exterior portions. The spherules, up to 2{ mm in Early chemical analyses of calculi frequently re- diameter, are dense intergrowths of radiating new- ported calcium carbonate as a stone constituent; beryite crystals, and when malformed they exist as this error resulted from the presenceof carbonate in rosettes and other splayed forms. Newberyite the apatite structure. Beck and Bender (1969) de- spherules usually amount to 10-20 percent of a scribed the first bona fide calcium carbonate urinary calculus by volume, but in some highly fragmented calculi, which included both calcite and aragonite. In calculi this p,roportion may be as high as 90 percent. the present study, calcite was found four times, al- Well-formed, vitreous, green, platy, diamond- ways as yellow to brown, granular, poorly consoli- shaped orthorhombic crystals constitute the second dated material not associatedwith other minerals' habit of newberyite. Such crystals are smaller than Two calculi composed of weddellite crystals de- 0.5 mm in length and are found on surfaces of posited on globular whewellite contained as a last apatite-struvite stones. These calculi are much more deposit colorless cubic crystals of halite. Calculi consolidated than those containing spherulesof new- which are stored in saline solutions sometimes are beryite but are otherwise similar. Occasionally, dia- encrusted after drying with a thin crust or scattered mond-shaped crystals are so tightly intergrown that powdery halite, but in the two cases observed the they form a thin, coherent shell encrusting all or part crystals were about 1l mm in size, and were inti- of the calculus. A unique and significant exception to mately intergrown with the angular weddellite crys- the associationwith apatite and struvite is a uric acid tals. No speculation as to the genesis of halite in stone encrusted with well-formed diamonds of new- the human body is offered at this time. beryite as large as 2 mm on an edge. This last in- Finally, two sulfates were identified in calculi. stance is evidencefor the precipitation of newberyite Gypsum, CaSO+'2H2O, occurred three times, always as the stable magnesium phosphate under acidic as fragile, colorless monoclinic crystals about 0.3 conditions in the urinarv svstem. mm long, on surfaces of calcium oxalate stones. DESCRIPTIVE HUMAN PATHOLOGICAL MINERALOGY I 181

Hexahydrite, MgSOa'6H2O, was identified in one another possible source for the necessarymultitude calculus containing newberyite, apatite, struvite, and of nuclei, but organisms are known to be present Mgg(PO+)z'4HrO. Hexahydrite can crystallize meta- and provide the simplest explanation. In the case of stably in contact with solution at human body tem- struvite, the large number of single crystalsin a stone peratures, but epsomite, MgSO, .7}J2O, is the stable may also reflect nucleation upon many centers com- phase. It is possible that the few poorly-bladed to posed of single organisms or small groups. (Based granular hexahydrite crystals in the stone dehydrated on actual cross-sectionalcrystal counts, over 7000 from epsomiteafter removal from the body. individual struvite crystals occur in a typical small (4 x l+ x I cm) apatite-struvitestaghorn calculus.) Non-urinary Pathological Minerals Struvite is almost invariably associatedwith apatite; Gall stones usually consist of organic compounds perhaps the magnesium phosphate is stabilized or such as cholesterol, but stones composed entirely or its precipitation catalyzed by the infective organism, in part of three calcium carbonate polymorphs as suggestedabove for newberyite. (calcite, aragonite, and vaterite) have been ob- served. As mentioned above, prostatic calculi are Simple Precipitates almost always whitlockite; some apatite may be Renal papillae are small protrusions within the associated.About 50 salivary gland stones analyzed kidney containing small ducts which transmit urine 'in this study were all pure, dense, porcelaneous, from the kidney tissue into large collecting chambers white-to-yellow apatite; a single tonsil stone was within the kidney. Tips of papillae are the site of powdery white apatite; and a single pancreascalculus initial deposition for more than one-third of all was calcite. The few calculi observed from the liver calculi, most of which contain calcium oxalates, and from joint deposits were all organic compounds. apatite, and brushite. The nucleus is invariably ex- ternal to the main part of the stone, and is almost Pathological Significance always very small with respect to the rest of the cal- Minerals in calculi are usually grouped according culus. Apatite, and less commonly, brushite, build up to their cations or anions or both. Ifowever, in the on the surfaces of papillae or within their ducts. following discussionof pathology the writer suggests Some urologists believe that small amounts of cal- two possible broad categories not based on major- cium phosphate at that location are normal. None- element chemistry: precipitates whose crystalliza- theless,these apatite and brushite buildups serve as tion is known or suspectedto be directly influenced the nuclei for many if not most papillary calculi. by minor elementsor infective organisms (catalyzed (Small external nuclei of apatite and brushite are precipitates), and those lacking such influences (sim- fragile, and may break away from a stone before ple precipitates). In addition to this speculation re- analysis.) Subsequently, whewellite in concentric garding initial precipitation, purely observational laminations is usually deposited,followed by dipyra- paragenetic data is incorporated. midal weddellite crystals. More apatite may deposit at any time, especially in crevices between globular C ataly Pr eci pitat zed es whewellite bodies or interstitial to weddellite crys- As discussed above, whitlockite precipitation is tals. Many large brushite calculi have papillary cavi- known to be aftected by small amounts of Mg and ties lined by apatite. Zn. Microprobe work in progress will hopefully un- Among calculi not deposited initially on renal cover the structural role of these elements,as well as papillae, apatite still is found as the most common providing quantitative information on amounts in- nucleus. Stones with whewellite nuclei are usually volved. pure whewellite, but they may have weddellite crys- The magnesium phosphatesall show evidence for tals on their surfaces. Weddellite is rarely found in origins closely related to the infections with which nuclei of stones. they are associated.Newberyite spherules are found All these "simple" precipitates are probably ac- scattered abundantly on stones' surfaces, and han- tually catalyzed to some extent by organic com- nayite laths radiate from many centers.This strongly pounds, both solid and liquid, which are ubiquitous suggeststhat individual crystalline aggregatesmay in the urinary system. In addition to the known role be deposited initially upon small concentrations of of organic material as a pigmenting agent, and its the infective organism. Large complex molecules are suspected influence in crystallization of glassy lt82 RICHARD I. GIBSON apatite,it may affectcrystallization and precipitation Urology, Vanderbilt University. In addition, S. W. Koehler, at the Indiana Uni- in other,unsuspected ways. The presenceof organic W. S. Cordua, I. Immega, and others versity Geology Department provided many useful ideas and mattershould never be ignoredin studiesof urinary assistance. minerals, although its effects are hard to evaluate. References Acknowledgments Brcx, C. W., eNo M. J. BpNosn (1969) Aragonite, CaCOa' This study was performed while the writer was employed as urinary calculi. I. Urol. l0l.r208-211. by Beck Analytical Services, Inc., Bloomington, Indiana, W. P. MurvANEY, AND R. K. Rrurvrv (1974) whose facilities were used and under whose auspicescalculi Monetite, CaHPO,, as urinary calculi. I. Urol. (in press). were obtained from doctors and hospitals; also, accessto HurroN, C. O., lxo W. H. Terr (1965) Weddellite in much unpublished work of the late Dr. Carl W. Beck, modern sediments,Florida. Mineral. Ma:g. 34,256-265. Indiana University Geology Department, was very bene- PnrrN, E. L., eNo C. FnoNonL (1947) Studiesin urolithiasis: ficial. For all this, my thanks to Beck Analytical and to I. The composition of urinary calculi. I' Urol' 57' 949- Mrs. Carl Beck. Pertinent clinical data was contributed in 99r. several stimulating discussionsby Drs. M. J. Sullivan and I. M. Palmer, Department of Urology, University of Cali- Manuscript receiued,April 18,1974; rccepted fornia, Davis, and by Dr. R. K. Rhamy, Department of lor publication,lune 25' 1974.