INTRODUÇÃO: A litíase biliar é uma doença do trato digestivo que apresenta prevalência variada em diferentes grupos étnicos e que gera altos gastos aos sistemas de saúde. A possibilidade de aplicação de tratamento não invasivo medicamentoso está direcionada a presença de cálculo de colesterol o que leva a necessidade de identificar corretamente os pacientes que podem beneficiar-se com o tratamento. No Brasil estima-se uma prevalência da doença em 9,3% da população em geral. Porém, ainda não há estudos que demonstrem a composição de cálculo de colesterol e pigmentos nos pacientes, bem como não há estudos de análise dos lipídios biliares e sua relação com os mecanismos fisiopatológicos da doença. Nossos objetivos foram analisar a composição do cálculo e da bile e compará-la com fatores pré-dispositivos da doença como tempo de nucleação e hiper saturação de colesterol em pacientes brasileiros. MÉTODOS: Foram analisadas 72 amostras de bile vesicular e cálculo biliar de pacientes com litíase biliar submetidos a procedimento cirúrgico laparoscópico em diferentes hospitais da grande São Paulo. Quatorze amostras de bile vesicular de pacientes que foram submetidos à laparoscopia por problemas gastrointestinais...
Bile acid kinetics and biliary lipid composition were characterized in six women with gallstones before and after 6 mo of oral therapy with chenodeoxycholic acid, an agent that induces dissolution of cholesterol gallstones in man. Over a dosage range of 1-4 g/day, absorption varied from 0.8 to 2.3 g/day. The chenodeoxycholic acid pool expanded two-to sixfold, and bile became composed predominantly (> 90%) of chenodeoxycholic acid conjugated chiefly with glycine. Cholic acid and deoxycholic acid pools decreased markedly, so that the total bile acid pool expanded much less, about twofold on the average. Cholic acid synthesis decreased in five of the six patients, consistent with negative feedback inhibition of cholic acid synthesis by chenodeoxycholic acid. In four patients whose bile was above or close to saturation with cholesterol, the bile became unsaturated; in two patients, whose bile was unsaturated, it remained so. In five patients with radiolucent gallstones, chenodeoxycholic acid therapy was continued after completion of kinetic and composition measurements; the stones decreased in size or dissolved entirely during the subsequent 6 to 18 mo. Similar measurements of bile acid kinetics and biliary lipid composition were made before and after a 6-mo period without medication in a control group of six healthy women; no changes occurred.
Black pigment, extracted from gallstones from patients, has been characterized as polybilirubinate. A similar material with the same physical properties was synthesized from bilirubin. The properties of black pigment are described. A mechanism for black pigment formation is postulated, and the possible relationship of this pigment to the formation of gallstones is discussed.
Bile composition and the presence of cholesterol crystals in bile were studied in bile samples obtained at the time of surgery in patients with ulcerative colitis. Some patients were sampled before colectomy and others at a second operation months to years after a colectomy. Patients in the precolectomy group were found to have bile composition similar to control patients without gallstones, and few had crystals in their bile. In the postcolectomy group, cholesterol concentrations were very high, all biles were supersaturated, and almost all patients had cholesterol crystals in their bile. These findings are similar to those found in persons with cholesterol gallstones. Twenty patients have been followed for at least 3 years after colectomy and to date three have formed cholesterol gallstones.
Detailed information on the structure and composition of gallstones was obtained using an electron probe microanalyser in conjunction with the other methods. Gallstones were studied layer by layer without greatly disturbing the arrangement of the materials present. Elements, including trace elements such as copper, iron, and manganese, were identified and their distributions mapped. The range of the method was extended to determine the character and distribution of certain chemical groups present by treating sections of gallstone with reagents which contained easily detected elements. The nature of the bonding of the sulphur in the stones was studied by examining the sulphur-X-ray spectrum. Pigmented sulphur-containing deposits were found to contain sulphur in a low valence state but taurine conjugates and the sulphate groups of mucosubstances were not detected. Microcrystalline apatite present in the stones contained some manganese and seemed to be implicated in the absorption of the low valence sulphur compound and in the nucleation of some stones.
It has been claimed that Rowachol, a proprietary choleretic, is occasionally successful in the treatment of gallstones. In gallstone patients we have examined its effect on the lipid composition of (1) samples of fasting gall bladder bile obtained at the time of cholecystectomy, and (2) T-tube bile on the tenth post-operative day. In a dose of two capsules, three times a day for only 48 hours, Rowachol significantly lowered the cholesterol solubility of both gall bladder (P less than 0.001) and T-tube bile (P less than 0.05). Rowachol in a dose of one capsule three times a day for 48 hours did not alter bile composition, while four capsules four times a day for a similar period caused a significant (P less than 0.05) deterioration in biliary lipid composition. The possible mechanisms of action of Rowachol and their therapeutic implications are discussed.
The crystalline constituents of gallstones determined by x-ray powder diffraction can be broadly classified as cholesterols and calcium salts. On this basis there are three main types of stones consisting of cholesterol, calcium salts, and mixtures of these. In a study of the composition of 481 gallstones from 11 countries, the percentage incidence of each was 59·9, 13·1, and 27·0 respectively. The presence of calcium compounds in 40·1% of the calculi showed the importance of these constituents in the nucleation and/or growth of many specimens. Men are just as likely as women to form stones consisting entirely of calcium salts, but female patients outnumber males by about 3:1 for both calculi of cholesterol and those of cholesterol with calcium salts. A description is given of the appearance, texture, and structure of calcium-containing stones subdivided according to the calcium salt(s) present.
Determination of the sequential deposition of crystalline compounds in a representative collection of gallstones from 578 patients has shown that a change in composition of gallstones containing both cholesterol and calcium salt(s) has frequently occurred during growth. Generally a central stone area composed of one of these types of compound is surrounded by outer layers formed of a mixture of both, or vice versa. In a few stones, however, there is a change from one type of compound to the other occurring in successive layers. Both in stones containing cholesterol and calcium salt(s) and in those consisting entirely of calcium salt, there is often also a change in the type of calcium salt present. Such changes provide indirect evidence of changes in gallbladder bile composition during growth of stones, the origin and mechanism of which are not understood.
The crystalline composition of two collections of gallstones from patients in England and Australia have been determined by the x-ray powder diffraction technique. Twelve substances have been identified including a form of cholesterol which hitherto has not been reported. The weighted percentage composition averaged over each collection shows that cholesterol is the major constituent of the Australian stones and cholesterol and cholesterol monohydrate the major constituents of the English calculi. The cholesterol is possibly a decomposition product of the monohydrate. The calcium carbonates—calcite, aragonite, and vaterite—constitute most of the remainder of the calculi. Although their percentage composition is much smaller than that of the cholesterols, they are nevertheless present in a high proportion of stones. Small traces of apatite, whitlockite, sodium chloride, calcium stearate and palmitic acid (or other long-chain compounds having closely related spacings) have been found. Small spheroids scattered throughout some stones appear to be mainly calcium stearate, although the total quantity available is too small and too impure for a definite identification.
Background—Chronic diarrhoea is the clinical
hallmark of patients presenting with idiopathic bile acid
malabsorption. Its pathogenesis is unknown; colonic water secretion can
be induced by dihydroxy bile acids, but it is not known whether
enrichment of the bile acid pool with these bile acids occurs in such
patients. Furthermore, bile acid malabsorption is known to affect
biliary lipid composition, but no information is available for the
idiopathic type. Aims—To verify: (a) whether
diarrhoea in patients with idiopathic bile acid malabsorption is
associated with enrichment of the bile acid pool with dihydroxy bile
acids; and (b) whether supersaturation with cholesterol of
duodenal bile occurs in such patients as a result of chronic bile acid depletion. Patients—Thirteen patients with idiopathic bile
acid malabsorption diagnosed according to abnormal 75SeHCAT
test and absence of other organic diseases, and 23 control subjects. Methods—Bile rich duodenal fluid was collected
during intravenous ceruletide infusion in the fasting state. Biliary
lipids were analysed by enzymatic assays and bile acids by high
performance liquid chromatography. Results—Patients with idiopathic bile acid
malabsorption had a cholesterol saturation index similar to controls.
Bile acid composition showed only a decrease in percentage cholic acid
(29(2)% versus 36 (2)%; p<0.05); the dihydroxy:trihydroxy bile acid ratio was similar to controls. Conclusions—Patients with idiopathic bile acid
malabsorption do not have an increased risk of forming cholesterol
gallstones. The mechanism of diarrhoea does not seem to depend on an
enrichment of the bile acid pool with dihydroxy bile acids.
BACKGROUND—Stimulated bile acid
synthesis preferentially utilises newly synthesised cholesterol,
raising the posssiblity that combination of simvastatin (an inhibitor
of cholesterol synthesis) with ursodeoxycholic acid (UDCA; a stimulator
of bile acid synthesis) may result in reduced bile acid synthesis and
greater enrichment of the pool with UDCA than that achieved with UDCA
treatment alone. AIMS—To investigate the effect of
simvastatin and UDCA given alone and in combination on serum and
biliary lipid and biliary bile acid composition. METHODS—Eighteen patients with
primary non-familial hypercholesterolaemia were studied during
treatment with simvastatin 20 mg/day, UDCA 10 mg/kg/day, and a
combination of the two drugs. Each regimen was given in random order
for three months following a three month lead in period. RESULTS—Simvastatin significantly
reduced serum low density lipoprotein (LDL) cholesterol but biliary
cholesterol concentration remained unchanged. Combination of the two
drugs had no synergistic effect on serum cholesterol concentration, but
significantly increased the proportion of UDCA in the bile acid pool
from 35% during UDCA to 48% during combination treatment (p<0.04). CONCLUSIONS—Results showed that:
(1) simvastatin reduces serum LDL cholesterol but has no effect on
biliary cholesterol concentration...
More women than men have cholesterol gallstones. This probably to a large extent owing to ovarian hormones. Our preliminary studies suggest that the biliary lipid composition and gallbladder function may be abnormal in pregnancy. Studies are in progress to clarify these suggestive changes. We hope that the studies will allow us to determine the relevance of pregnancy to the pathogenesis of cholesterol gallstones.
The composition of fasting hepatic bile was analyzed in 63 samples from 8 patients following cholecystectomy to determine if bile was lithogenic in patients with previous cholesterol gallstones after removal of the gallbladder. Bile specimens were obtained from t-tubes over a 7-20 day study period following re-establishment of the enterohepatic circulation. Bile composition varied on a day to day basis in each patient. 18 of 63 samples were lithogenic according to criteria of Admirand and Small while 35 of 63 samples were lithogenic according to criteria of Hegardt and Dam. Variations in the composition of hepatic bile appeared related to changes in the excretion rate of bile acids. These studies demonstrate that hepatic bile may be lithogenic after cholecystectomy and indicate that factors other than sequestration of the bile acid pool in the gallbladder influence the enterohepatic circulation of bile acids and the lithogenicity of bile.
Gallstone disease is one of the major surgical problems in the Libyan population; it is probably related to diet, especially excessive consumption of meat. The study was conducted to determine the composition of gallstones and their possible etiology in a Libyan population. The chemical composition of gallstones from 41 patients (six males and 35 females) was analyzed. The stones were classified into cholesterol, pigment, and mixed stones (MS). Cholesterol stones (CS) showed a significantly higher cholesterol content than pigment stones (PS) (p=0.0085) though not significantly higher than MS. Their phospholipid content and inorganic phosphates were higher than in the other types of stones and oxalate content was significantly elevated in comparison with MS (p=0.0471). In MS, the cholesterol, bile acids, and bilirubin were intermediate between cholesterol and PS, whereas triglycerides were significantly more than PS (p=0.0004). Bilirubin (0.0001) and bile acids (p=0.0009) were significantly higher than CS (p=0.0001). However, they contained the lowest amounts of sodium, potassium, magnesium, and oxalate. In PS, bilirubin (p=0.0001) was significantly higher than both groups. Bile acid content was significantly higher than CS (p=0.0001) but not significantly more than MS. They showed the highest values of calcium...
In a survey of 430 Lori-Bakhtiari sheep at a slaughterhouse in Iran, gallstones were found in the gallbladder of 7 sheep (1.6%). Biliary calculi were more frequent in adult and female sheep (P < 0.05). Chemical analysis of the gallstones revealed 6 sheep with pigment (bilirubin) stones and 1 sheep with cholesterol stones. Chemical composition of bile in these sheep was evaluated. Bacteriologic analysis of the bile in the affected sheep revealed bacteria (Streptococcus spp., Klebsiella spp., Escherichia coli, and Salmonella spp.) in 5 sheep. Microscopic examination of gallbladders revealed focal calcification, cystic glands, necrosis and atrophy of mucosal layer, edema, diffuse and focal infiltration of lymphocytes in submucosal layer, and hypertrophy of smooth muscles in sheep with gallstones. It was concluded that the prevalence of both types of gallstones in Lori-Bakhtiari sheep is low. Cholelithiasis can cause chronic inflammation of the gallbladder, but it is not likely to become clinically significant.
Chronic carriage of Salmonella Typhi is mediated primarily through the formation of bacterial biofilms on the surface of cholesterol gallstones. Biofilms, by definition, involve the formation of a bacterial community encased within a protective macromolecular matrix. Previous work has demonstrated the composition of the biofilm matrix to be complex and highly variable in response to altered environmental conditions. Although known to play an important role in bacterial persistence in a variety of contexts, the Salmonella biofilm matrix remains largely uncharacterized under physiological conditions. Initial attempts to study matrix components and architecture of the biofilm matrix on gallstone surfaces were hindered by the auto-fluorescence of cholesterol. In this work we describe a method for sectioning and direct visualization of extracellular matrix components of the Salmonella biofilm on the surface of human cholesterol gallstones and provide a description of the major matrix components observed therein. Confocal micrographs revealed robust biofilm formation, characterized by abundant but highly heterogeneous expression of polysaccharides such as LPS, Vi and O-antigen capsule. CsgA was not observed in the biofilm matrix and flagellar expression was tightly restricted to the biofilm-cholesterol interface. Images also revealed the presence of preexisting Enterobacteriaceae encased within the structure of the gallstone. These results demonstrate the use and feasibility of this method while highlighting the importance of studying the native architecture of the gallstone biofilm. A better understanding of the contribution of individual matrix components to the overall biofilm structure will facilitate the development of more effective and specific methods to disrupt these bacterial communities.
The crystalline composition of gallstones from Australia, England, Germany, India, Kuwait, South Africa, Sweden, and the USA has now been determined by the x-ray powder method. Eleven compounds were identified. The three cholesterols—cholesterol monohydrate, anhydrous cholesterol, and cholesterol II—account for 71% of the total crystalline material in the stones; the calcium carbonates—vaterite, aragonite, and calcite—contribute 15%, and calcium palmitate contributes 6%. Smaller amounts of apatite, sodium chloride, whitlockite, and α-palmitic acid were also found. The composition distribution in each country is significantly different. Gallstones from Germany, Sweden, and Australia are the most similar. Gallstones from England have significantly more carbonate, and stones from South Africa have much less cholesterol and more calcium phosphate and calcium palmitate. Stones from Kuwait have a large amount of calcium palmitate and those from India an excess of calcium phosphate. The composition of stones related to the age and to the sex of a patient shows that although there are no significant differences in composition for patients under and over the age of 50 there are differences in the stone composition related to the patient's sex. Female patients form much more cholesterol while males form much more calcium palmitate and slightly more calcium carbonate. The differences also exist for female and male patients over and under 50 years of age. A study of the texture and orientation of the crystalline material in the gallstones has shown that anhydrous cholesterol and cholesterol monohydrate can occur as single crystals oriented with respect to the nucleus whereas other stone components are disoriented crystallites.
Bile specimens were obtained from 17 patients with gallstones and 21 patients with duodenal ulcer. The specimens were obtained from the former by needle aspiration of the gallbladder and common bile duct at operation and from the latter by duodenal intubation. The concentrations of bile salt, phospholipid, and cholesterol were measured. Gallbladder bile from gallstone patients contained significantly more cholesterol than did `duodenal' bile from duodenal ulcer patients. Hepatic bile from gallstone patients contained significantly more cholesterol than did gallbladder bile from the same patients. When the data were plotted on triangular coordinates the relative composition lay within the zone of cholesterol solubility in all 21 ulcer patients. The relative composition of hepatic bile lay outside the zone of cholesterol solubility in five gallstone patients, at the limits of cholesterol solubility in a further three, and within the micellar zone in the remaining nine patients. This suggests that supersaturation of hepatic bile with cholesterol is not the sine qua non for the production of cholesterol gallstones.
Abnormally low activity of hepatic bilirubin UDP-glucuronosyltransferase was found in 25% of 81 unselected patients with gallstones, as compared with only 3% in 35 controls. At the time of cholecystectomy, the stones were taken for analysis in 48 of 81 patients, and a bile sample was obtained in 42 of them. Among the stones, 75% were cholesterol stones, 15% pigment stones, and 10% 'intermediate' stones. Low hepatic conjugating activity was not preferentially associated with a given type of stone. No relation was found between the enzymic deficiency and the biliary cholesterol saturation index. A high proportion of biliary bilirubin monoglucuronide (over 40%) was found in four of seven patients with low transferase activity, as was earlier demonstrated in patients with overt Gilbert's syndrome. Raised biliary bilirubin monoglucuronide was also found in three patients, out of 46, who had normal transferase but raised biliary beta-glucuronidase activity. There was no evidence that deficient bilirubin conjugation could be a consequence of gallstones: the activity of another hepatic microsomal enzyme, glucose 6-phosphatase, taken as a reference, was measured in 12 patients and was always normal. Taking into account the very high frequency of a bilirubin centre in the cholesterol stones (87% of the cases in the present series)...
The stability of albumin-bilirubin complex was investigated depending on pH
of solution. It was shown that the stability of complex increases in presence
of Mn(II) ions. It was also investigated the paramagnetic composition of
gallstones by the electron spin resonance (ESR) method. It turned out that all
investigated gallstones contain a free bilirubin radical-the stable product of
its radical oxidation. Accordingly the paramagnetic composition gallstones
could be divided on three main types: cholesterol, brown pigment and black
pigment stones. ESR spectra of cholesterol stones is singlet with g=2.003 and
splitting between components 1.0 mT. At the same time the brown gallstones,
besides aforementioned signal contain the ESR spectrum which is characteristics
for Mn(II) ion complexes with inorganic compounds and, finally, in the black
pigment stones it was found out Fe(III) and Cu(II) complexes with organic
compounds and a singlet of bilirubin free radical. It is supposed that
crystallization centers of gallstones could be the polymer network of bilirubin
radical polymerization in complex with different metal ions earlier discovered
in gallstones.; Comment: 12 pages, 6 figures