Materiały źródłowe

• #1 Concept of the pathogenesis and treatment of cholelithiasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3295849/

  Gallstone disease (GD) is a chronic recurrent hepatobiliary disease, the basis for which is the impaired metabolism of cholesterol, bilirubin and bile acids, which is characterized by the formation of gallstones in the hepatic bile duct, common bile duct, or gallbladder. […] The pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental factors. […] Cholesterol GD results from a biochemical imbalance of lipids and bile salts in the gallbladder bile. […] The pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental factors. […] Cholesterol stones are formed in the gallbladder due to impaired relationships between the major bile components, cholesterol, phospholipids and bile acids.

• #2 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  Gallstones are the stones developing in the gallbladder. Evolution of pathophysiology changes the trends of treatment of a disease. There are mainly three types of stones Cholesterol, pigment and brown stones. The pathophysiology of which is different for each type. Cholesterol stones being most common owing to the risk factors being prevalent in the developing and developed societies. Pigment stones being most common in blood disorder patients while brown stones are most common in common bile duct and are infected ones. […] The gallstones are hard, pebble-like pieces of material, usually made of cholesterol or bilirubin, that develop in the gallbladder. These stones are formed due to various disorders. Five defects primarily play critical role in pathogenesis of cholesterol stones Viz lithogenes and genetic factors; hepatic hypersecretion of cholesterol; rapid phase transition of cholesterol in bile; impaired gallbladder motility; intestinal factors involving absorption of cholesterol, slow intestinal motility and altered gut microbiota.

• #3 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  Gallstones are the stones developing in the gallbladder. Evolution of pathophysiology changes the trends of treatment of a disease. There are mainly three types of stones Cholesterol, pigment and brown stones. The pathophysiology of which is different for each type. Cholesterol stones being most common owing to the risk factors being prevalent in the developing and developed societies. Pigment stones being most common in blood disorder patients while brown stones are most common in common bile duct and are infected ones. […] The gallstones are hard, pebble-like pieces of material, usually made of cholesterol or bilirubin, that develop in the gallbladder. These stones are formed due to various disorders. Five defects primarily play critical role in pathogenesis of cholesterol stones Viz lithogenes and genetic factors; hepatic hypersecretion of cholesterol; rapid phase transition of cholesterol in bile; impaired gallbladder motility; intestinal factors involving absorption of cholesterol, slow intestinal motility and altered gut microbiota.

• #4 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  There are three types of gallstones; first and most common type is cholesterol stone. Black and brown pigmented stones are the other two types of gallstones. The prevalence of various types of gallstones in the western world is: 75% of gallstones are cholesterol stones, 20% are black pigment stones, and 5% or less are brown pigment stones. Cholesterol and black pigment stones are formed exclusively in gallbladder in a sterile medium, while as brown pigment stones are formed everywhere in the biliary tree owing to the anaerobic bacterial infection. Stasis of bile is an essential component in the formation of gallstone or bile duct stone formation. […] Physical-chemical origin is the basis of pathogenesis of sterile stones (cholesterol and black pigment stones). There is an alteration in lipid and lipo-pigment composition which results in the formation of stones. In cholesterol and black pigment stones the major component is cholesterol monohydrate crystals and calcium hydrogen bilirubinate respectively. During the long stay in gallbladder, the black pigment gets degraded and polymerized by free radicals and helps in the formation of black pigment stones while as in the brown pigment stones the main mechanism is infectious where the enzymatic hydrolysis of biliary lipids by anaerobic bacterial enzymes produces supersaturated long chain fatty and deconjugated bile acids.

• #5 Concept of the pathogenesis and treatment of cholelithiasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3295849/

  Gallstone disease (GD) is a chronic recurrent hepatobiliary disease, the basis for which is the impaired metabolism of cholesterol, bilirubin and bile acids, which is characterized by the formation of gallstones in the hepatic bile duct, common bile duct, or gallbladder. […] The pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental factors. […] Cholesterol GD results from a biochemical imbalance of lipids and bile salts in the gallbladder bile. […] The pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental factors. […] Cholesterol stones are formed in the gallbladder due to impaired relationships between the major bile components, cholesterol, phospholipids and bile acids.

• #6 Pathogenesis of gallstones – PubMed

  https://pubmed.ncbi.nlm.nih.gov/8480873/

  Gallstones form as a result of many disorders. Unphysiologic supersaturation, generally from hypersecretion of cholesterol, is essential for the formation of cholesterol gallstones. […] The other common abnormalities of the hepatobiliary system in gallstone patients are accelerated nucleation, gallbladder hypomotility, and the accumulation of mucin gel. […] Supersaturation of bile with calcium hydrogen bilirubinate, the acid calcium salt of unconjugated bilirubin, is essential for pigment gallstone formation, but its magnitude remains undefined in model systems. […] Nucleation and the precipitation of calcium hydrogen bilirubinate with the polymerization of the pigment in the gallbladder, together with the deposition of the inorganic salts, calcium carbonate and phosphate, result in black pigment gallstone formation.

• #7 Gallbladder Stones – Pathogenesis and Treatment | IntechOpen

  https://www.intechopen.com/chapters/1147362

  Gallstone disease (GSD) refers to all the patients with symptoms due to gallstones (cholelithiasis). […] There are several mechanism for cholelithiasis and all these processes are slow. Cholesterol stones are the most common variety of gallstones. Cholesterol stones cannot form if the gallbladder is completely emptied several times a day. Therefore, the total or partial extension of bile storage due to impaired gallbladder movement seems to be an important factor for cholelithiasis. Gallbladder dysmotility is an important risk factor for the development of GSD. […] The pathogenesis of gallstones are multifactorial including a variety of genetic and environmental factors. The local factors in the gall bladder include gallbladder dysmotility, hypersecretion and accumulation of mucin gel in the gall bladder lumen. The local factors in the bile consists of rapid phase transition of cholesterol from supersaturated hepatic bile and local immune mediated inflammation in the gallbladder.

• #8 Concept of the pathogenesis and treatment of cholelithiasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3295849/

  The important factor in such mesophasic nucleation is associated with further interaction between the monohydrate crystals and the molecules of protein and unconjugated bilirubin. […] Chronic inflammation of the gallbladder wall and mucin hypersecretion are considered important factors in the pathogenesis of cholesterol GD. […] The observed increase in the activity of the phospholipase 2 secreted by bacteria leads to the hydrolysis of phospholipids and the accumulation of free fatty acids, including arachidonic acid. […] The latter activates the generation of prostaglandins, thromboxanes and leukotrienes to cause mucin glycoproteins to be hypersecreted by the gallbladder mucosa. […] The genetic material of Clonorchis sinensis and Ascaris lumbricoides worms may be found in the GS. […] The pathophysiology of GS formation involves three steps: saturation, crystallization and growth.

• #9 Management of Gallstones and Their Complications | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0315/p1673.html

  Gallstones found in the gallbladder are classified as cholesterol, pigmented or mixed stones, based on their chemical composition. Up to 90 percent of gallstones are cholesterol (more than 50 percent cholesterol) or mixed (20 to 50 percent cholesterol) gallstones. The remaining 10 percent of gallstones are pigmented stones, which have less than 20 percent cholesterol. […] The basic mechanism underlying the formation of gallstones is supersaturation, with constituents in bile exceeding their maximum solubilities. Additional factors contributing to gallstone formation are nucleation factors, bile stasis within the gallbladder and calcium in bile. Biliary cholesterol usually exists in a soluble single phase as micellar cholesterol. As the cholesterol concentration increases, cholesterol crystals begin to form.

• #10 Pathogenesis of Gallstones | Abdominal Key

  https://abdominalkey.com/pathogenesis-of-gallstones-2/

  Cholesterol gallstone formation is a complex process and involves phase separation of cholesterol crystals from supersaturated bile. In most cases, cholesterol hypersecretion is considered the primary event in gallstone formation. […] Cholesterol crystal nucleation is considered the earliest step in cholesterol gallstone formation. Various conditions affecting the crystallization process are discussed, such as biliary cholesterol supersaturation, excess pronucleating proteins, or shortage of nucleation-inhibiting proteins, and factors related to the gallbladder, such as hypomotility. […] Cholesterol crystal nucleation is thought to occur in general from vesicles supersaturated with cholesterol (ie, vesicular cholesterol/phospholipid ratio 1). First, small unilamellar supersaturated vesicles aggregate or fuse into larger multilamellar vesicles (liquid crystals), with subsequent phase-separation of cholesterol crystals.

• #11 Cholelithiasis – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/gallbladder-and-bile-duct-disorders/cholelithiasis

  The excess cholesterol must precipitate from solution as solid microcrystals. Such precipitation in the gallbladder is accelerated by mucin, a glycoprotein, or other proteins in bile. […] The microcrystals must aggregate and grow. This process is facilitated by the binding effect of mucin forming a scaffold and by retention of microcrystals in the gallbladder with impaired contractility due to excess cholesterol in bile. […] Gallstones grow at about 1 to 2 mm/year, taking 5 to 20 years before becoming large enough to cause problems. Most gallstones form within the gallbladder, but brown pigment stones form in the ducts. Gallstones may migrate to the bile duct after cholecystectomy or, particularly in the case of brown pigment stones, develop behind strictures as a result of stasis and infection.

• #12 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  Various defects occur simultaneously for the nucleation and crystallization of cholesterol monohydrate viz unphysiological supersaturation with cholesterol, accelerated nucleation and gallbladder hypomotility. The mucin glycoprotein hypersecretion follows and lead to the stone formation. Excessive secretion of cholesterol into bile leads to cholesterol supersaturation owing to multiple biochemical defects either from increased input (de novo synthesis, lipoprotein uptake) or decreased disposition (de novo bile salt and cholesteryl ester synthesis). […] Black stones occur in sterile environment with increased frequency in patients of chronic haemolysis. A shift in ratio of bilirubin diconjugates to the favour of monoconjugates especially monoglucuronides occur due to hypersecretion of bilirubin conjugates in bile. Bile pigment output increases by 10-fold with haemolysis and predominantly becomes monoconjugates that are more hydrolysed by endogenous glucuronidase.

• #13 Factors Influencing Gallstone Formation: A Review of the Literature

  https://www.mdpi.com/2218-273X/12/4/550

  Gallstone disease is a common pathology of the digestive system with nearly a 10–20% incidence rate among adults. […] Clinical research suggests that cholelithiasis is closely related to the age, gender, body mass index, and other basic physical characteristics of patients. […] Clinical research further suggests that the occurrence of cholelithiasis is related to obesity, diabetes, non-alcoholic fatty liver, and other diseases. […] Herein, we summarize and analyze the causes and mechanisms of cholelithiasis, discuss its correlation with the pathogenesis of related diseases, and discuss possible mechanisms. […] In 2010, five factors were proposed to promote the formation of gallstones. These include genetic factors; excessive liver cholesterol secretion (resulting in cholesterol supersaturation in gallbladder bile); factors that accelerate the growth of cholesterol crystals and solid cholesterol crystals; impairment of gallbladder motility; and intestinal factors.

• #14 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  Gallstones are hard, pebble-like structures that obstruct the cystic duct. The formation of gallstones is often preceded by the presence of biliary sludge, a viscous mixture of glycoproteins, calcium deposits, and cholesterol crystals in the gallbladder or biliary ducts. In the U.S., most gallstones consist largely of bile supersaturated with cholesterol. This hypersaturation, which results from the cholesterol concentration being greater than its solubility percentage, is caused primarily by hypersecretion of cholesterol due to altered hepatic cholesterol metabolism. A distorted balance between pronucleating (crystallization-promoting) and antinucleating (crystallization-inhibiting) proteins in the bile also can accelerate crystallization of cholesterol in the bile. Mucin, a glycoprotein mixture secreted by biliary epithelial cells, has been documented as a pronucleating protein. It is the decreased degradation of mucin by lysosomal enzymes that is believed to promote the formation of cholesterol crystals. […]

• #15 Management of Gallstones and Their Complications | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0315/p1673.html

  Gallstones found in the gallbladder are classified as cholesterol, pigmented or mixed stones, based on their chemical composition. Up to 90 percent of gallstones are cholesterol (more than 50 percent cholesterol) or mixed (20 to 50 percent cholesterol) gallstones. The remaining 10 percent of gallstones are pigmented stones, which have less than 20 percent cholesterol. […] The basic mechanism underlying the formation of gallstones is supersaturation, with constituents in bile exceeding their maximum solubilities. Additional factors contributing to gallstone formation are nucleation factors, bile stasis within the gallbladder and calcium in bile. Biliary cholesterol usually exists in a soluble single phase as micellar cholesterol. As the cholesterol concentration increases, cholesterol crystals begin to form.

• #16 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  Gallstones are hard, pebble-like structures that obstruct the cystic duct. The formation of gallstones is often preceded by the presence of biliary sludge, a viscous mixture of glycoproteins, calcium deposits, and cholesterol crystals in the gallbladder or biliary ducts. In the U.S., most gallstones consist largely of bile supersaturated with cholesterol. This hypersaturation, which results from the cholesterol concentration being greater than its solubility percentage, is caused primarily by hypersecretion of cholesterol due to altered hepatic cholesterol metabolism. A distorted balance between pronucleating (crystallization-promoting) and antinucleating (crystallization-inhibiting) proteins in the bile also can accelerate crystallization of cholesterol in the bile. Mucin, a glycoprotein mixture secreted by biliary epithelial cells, has been documented as a pronucleating protein. It is the decreased degradation of mucin by lysosomal enzymes that is believed to promote the formation of cholesterol crystals. […]

• #17 Pathogenesis of Gallstones | Abdominal Key

  https://abdominalkey.com/pathogenesis-of-gallstones-2/

  Cholesterol gallstone formation is a complex process and involves phase separation of cholesterol crystals from supersaturated bile. In most cases, cholesterol hypersecretion is considered the primary event in gallstone formation. […] Cholesterol crystal nucleation is considered the earliest step in cholesterol gallstone formation. Various conditions affecting the crystallization process are discussed, such as biliary cholesterol supersaturation, excess pronucleating proteins, or shortage of nucleation-inhibiting proteins, and factors related to the gallbladder, such as hypomotility. […] Cholesterol crystal nucleation is thought to occur in general from vesicles supersaturated with cholesterol (ie, vesicular cholesterol/phospholipid ratio 1). First, small unilamellar supersaturated vesicles aggregate or fuse into larger multilamellar vesicles (liquid crystals), with subsequent phase-separation of cholesterol crystals.

• #18 Pathogenesis of Gallstones | Abdominal Key

  https://abdominalkey.com/pathogenesis-of-gallstones-2/

  Cholesterol gallstone formation is a complex process and involves phase separation of cholesterol crystals from supersaturated bile. In most cases, cholesterol hypersecretion is considered the primary event in gallstone formation. […] Cholesterol crystal nucleation is considered the earliest step in cholesterol gallstone formation. Various conditions affecting the crystallization process are discussed, such as biliary cholesterol supersaturation, excess pronucleating proteins, or shortage of nucleation-inhibiting proteins, and factors related to the gallbladder, such as hypomotility. […] Cholesterol crystal nucleation is thought to occur in general from vesicles supersaturated with cholesterol (ie, vesicular cholesterol/phospholipid ratio 1). First, small unilamellar supersaturated vesicles aggregate or fuse into larger multilamellar vesicles (liquid crystals), with subsequent phase-separation of cholesterol crystals.

• #19 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  Gallstones are hard, pebble-like structures that obstruct the cystic duct. The formation of gallstones is often preceded by the presence of biliary sludge, a viscous mixture of glycoproteins, calcium deposits, and cholesterol crystals in the gallbladder or biliary ducts. In the U.S., most gallstones consist largely of bile supersaturated with cholesterol. This hypersaturation, which results from the cholesterol concentration being greater than its solubility percentage, is caused primarily by hypersecretion of cholesterol due to altered hepatic cholesterol metabolism. A distorted balance between pronucleating (crystallization-promoting) and antinucleating (crystallization-inhibiting) proteins in the bile also can accelerate crystallization of cholesterol in the bile. Mucin, a glycoprotein mixture secreted by biliary epithelial cells, has been documented as a pronucleating protein. It is the decreased degradation of mucin by lysosomal enzymes that is believed to promote the formation of cholesterol crystals. […]

• #20 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  Gallstones are hard, pebble-like structures that obstruct the cystic duct. The formation of gallstones is often preceded by the presence of biliary sludge, a viscous mixture of glycoproteins, calcium deposits, and cholesterol crystals in the gallbladder or biliary ducts. In the U.S., most gallstones consist largely of bile supersaturated with cholesterol. This hypersaturation, which results from the cholesterol concentration being greater than its solubility percentage, is caused primarily by hypersecretion of cholesterol due to altered hepatic cholesterol metabolism. A distorted balance between pronucleating (crystallization-promoting) and antinucleating (crystallization-inhibiting) proteins in the bile also can accelerate crystallization of cholesterol in the bile. Mucin, a glycoprotein mixture secreted by biliary epithelial cells, has been documented as a pronucleating protein. It is the decreased degradation of mucin by lysosomal enzymes that is believed to promote the formation of cholesterol crystals. […]

• #21 Management of Gallstones and Their Complications | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0315/p1673.html

  Mucin and a soluble glycoprotein are potential nucleation factors. Prostaglandins stimulate the synthesis and secretion of bile mucin. Inflammation and other stimuli, which enhance prostaglandin secretion, increase the risk for gallstone formation. Biliary sludge, also referred to as microlithiasis, is a viscous gel composed of mucin, precipitates of cholesterol and calcium bilirubinate. Gallstone formation is usually preceded by the presence of biliary sludge. Therefore, sludge should be regarded as part of the spectrum of gallstone disease. Retarded or incomplete emptying of bile from the gallbladder can promote sludge formation. The risk factors for gallstone formation are summarized in Table 1. […] People with diabetes have a propensity for obesity, hypertriglyceridemia and gallbladder hypomotility. Therefore, it has been difficult to prove that diabetes is an independent risk factor for gallstone formation. However, some studies have shown an increased prevalence (without statistical significance) of diabetes in patients with gallstones.

• #22 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  Gallstones are hard, pebble-like structures that obstruct the cystic duct. The formation of gallstones is often preceded by the presence of biliary sludge, a viscous mixture of glycoproteins, calcium deposits, and cholesterol crystals in the gallbladder or biliary ducts. In the U.S., most gallstones consist largely of bile supersaturated with cholesterol. This hypersaturation, which results from the cholesterol concentration being greater than its solubility percentage, is caused primarily by hypersecretion of cholesterol due to altered hepatic cholesterol metabolism. A distorted balance between pronucleating (crystallization-promoting) and antinucleating (crystallization-inhibiting) proteins in the bile also can accelerate crystallization of cholesterol in the bile. Mucin, a glycoprotein mixture secreted by biliary epithelial cells, has been documented as a pronucleating protein. It is the decreased degradation of mucin by lysosomal enzymes that is believed to promote the formation of cholesterol crystals. […]

• #23 Concept of the pathogenesis and treatment of cholelithiasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3295849/

  The important factor in such mesophasic nucleation is associated with further interaction between the monohydrate crystals and the molecules of protein and unconjugated bilirubin. […] Chronic inflammation of the gallbladder wall and mucin hypersecretion are considered important factors in the pathogenesis of cholesterol GD. […] The observed increase in the activity of the phospholipase 2 secreted by bacteria leads to the hydrolysis of phospholipids and the accumulation of free fatty acids, including arachidonic acid. […] The latter activates the generation of prostaglandins, thromboxanes and leukotrienes to cause mucin glycoproteins to be hypersecreted by the gallbladder mucosa. […] The genetic material of Clonorchis sinensis and Ascaris lumbricoides worms may be found in the GS. […] The pathophysiology of GS formation involves three steps: saturation, crystallization and growth.

• #24 Concept of the pathogenesis and treatment of cholelithiasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3295849/

  The important factor in such mesophasic nucleation is associated with further interaction between the monohydrate crystals and the molecules of protein and unconjugated bilirubin. […] Chronic inflammation of the gallbladder wall and mucin hypersecretion are considered important factors in the pathogenesis of cholesterol GD. […] The observed increase in the activity of the phospholipase 2 secreted by bacteria leads to the hydrolysis of phospholipids and the accumulation of free fatty acids, including arachidonic acid. […] The latter activates the generation of prostaglandins, thromboxanes and leukotrienes to cause mucin glycoproteins to be hypersecreted by the gallbladder mucosa. […] The genetic material of Clonorchis sinensis and Ascaris lumbricoides worms may be found in the GS. […] The pathophysiology of GS formation involves three steps: saturation, crystallization and growth.

• #25 Pathogenesis of gallstones – PubMed

  https://pubmed.ncbi.nlm.nih.gov/8480873/

  On the basis of ex vivo muscle studies, gallbladder hypomotility is unlikely in patients with black pigment stones but is invariably present in patients with cholesterol stones. […] Pigment supersaturation in the gallbladder is the result of hepatic hypersecretion of bilirubin conjugates in hemolytic disorders and possibly enterohepatic cycling of unconjugated bilirubin in nonhemolytic states. […] Less common is bile salt hyposecretion from impaired synthesis in constitutional disorders and cirrhosis, and uncompensated interruption of the enterohepatic circulation in ileal dysfunction syndromes. […] Bile salt deficiency causes incomplete solubilization of unconjugated bilirubin and impaired binding of calcium ions. […] Stasis and anaerobic bacterial infection are responsible for brown pigment stones, which usually form in the bile ducts. […] In addition to the precipitation of calcium hydrogen bilirubinate that remains unpolymerized, there is also the deposition of the calcium salts of saturated fatty acids and free bile acids, both of which are the result of bacterial enzymatic hydrolysis of biliary lipids.

• #26 Gallbladder Stones – Pathogenesis and Treatment | IntechOpen

  https://www.intechopen.com/chapters/1147362

  Gallstone disease (GSD) refers to all the patients with symptoms due to gallstones (cholelithiasis). […] There are several mechanism for cholelithiasis and all these processes are slow. Cholesterol stones are the most common variety of gallstones. Cholesterol stones cannot form if the gallbladder is completely emptied several times a day. Therefore, the total or partial extension of bile storage due to impaired gallbladder movement seems to be an important factor for cholelithiasis. Gallbladder dysmotility is an important risk factor for the development of GSD. […] The pathogenesis of gallstones are multifactorial including a variety of genetic and environmental factors. The local factors in the gall bladder include gallbladder dysmotility, hypersecretion and accumulation of mucin gel in the gall bladder lumen. The local factors in the bile consists of rapid phase transition of cholesterol from supersaturated hepatic bile and local immune mediated inflammation in the gallbladder.

• #27 Gallbladder Stones – Pathogenesis and Treatment | IntechOpen

  https://www.intechopen.com/chapters/1147362

  Cholesterol gallstones cannot form if the gallbladder is completely emptied several times a day. Therefore, gallbladder dysmotility seems to be an important factor for cholelithiasis. Gallbladder dysmotility may be attributed to decreased sensitivity of the gallbladder to CCK. It has been observed that ICLCs density is markedly reduced in the gallbladder with stones. The reduced density of ICLCs decreases the gallbladder motility. […] The mechanism of gallstone formation amongst the various types of gallstones are mentioned below. […] The bile is concentrated 34 folds in the gallbladder due to water absorption and progressively increasing cholesterol in the micelle due to the preferential solubilization of bile salts with phospholipids leaving supersaturated bile cause cholesterol nucleation and this explains why the gallstones are usually seen in gallbladder than anywhere else in the biliary tree. […] Gallbladder dysmotility is another important factor for the development of cholesterol nucleation, since it causes stagnation of bile leading to crystal aggregation.

• #28 Gallbladder Stones – Pathogenesis and Treatment | IntechOpen

  https://www.intechopen.com/chapters/1147362

  Cholesterol gallstones cannot form if the gallbladder is completely emptied several times a day. Therefore, gallbladder dysmotility seems to be an important factor for cholelithiasis. Gallbladder dysmotility may be attributed to decreased sensitivity of the gallbladder to CCK. It has been observed that ICLCs density is markedly reduced in the gallbladder with stones. The reduced density of ICLCs decreases the gallbladder motility. […] The mechanism of gallstone formation amongst the various types of gallstones are mentioned below. […] The bile is concentrated 34 folds in the gallbladder due to water absorption and progressively increasing cholesterol in the micelle due to the preferential solubilization of bile salts with phospholipids leaving supersaturated bile cause cholesterol nucleation and this explains why the gallstones are usually seen in gallbladder than anywhere else in the biliary tree. […] Gallbladder dysmotility is another important factor for the development of cholesterol nucleation, since it causes stagnation of bile leading to crystal aggregation.

• #29 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  Loss of gallbladder muscular-wall motility and excessive sphincteric contraction also are involved in gallstone formation. This hypomotility leads to prolonged bile stasis (delayed gallbladder emptying), along with decreased reservoir function. The lack of bile flow causes an accumulation of bile and an increased predisposition for stone formation. Ineffective filling and a higher proportion of hepatic bile diverted from the gallbladder to the small bile duct can occur as a result of hypomotility. […] […] Occasionally, gallstones are composed of bilirubin, a chemical that is produced as a result of the standard breakdown of RBCs. Infection of the biliary tract and increased enterohepatic cycling of bilirubin are the suggested causes of bilirubin stone formation. Bilirubin stones, often referred to as pigment stones, are seen primarily in patients with infections of the biliary tract or chronic hemolytic diseases (or damaged RBCs). […]

• #30 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  Loss of gallbladder muscular-wall motility and excessive sphincteric contraction also are involved in gallstone formation. This hypomotility leads to prolonged bile stasis (delayed gallbladder emptying), along with decreased reservoir function. The lack of bile flow causes an accumulation of bile and an increased predisposition for stone formation. Ineffective filling and a higher proportion of hepatic bile diverted from the gallbladder to the small bile duct can occur as a result of hypomotility. […] […] Occasionally, gallstones are composed of bilirubin, a chemical that is produced as a result of the standard breakdown of RBCs. Infection of the biliary tract and increased enterohepatic cycling of bilirubin are the suggested causes of bilirubin stone formation. Bilirubin stones, often referred to as pigment stones, are seen primarily in patients with infections of the biliary tract or chronic hemolytic diseases (or damaged RBCs). […]

• #31 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  Loss of gallbladder muscular-wall motility and excessive sphincteric contraction also are involved in gallstone formation. This hypomotility leads to prolonged bile stasis (delayed gallbladder emptying), along with decreased reservoir function. The lack of bile flow causes an accumulation of bile and an increased predisposition for stone formation. Ineffective filling and a higher proportion of hepatic bile diverted from the gallbladder to the small bile duct can occur as a result of hypomotility. […] […] Occasionally, gallstones are composed of bilirubin, a chemical that is produced as a result of the standard breakdown of RBCs. Infection of the biliary tract and increased enterohepatic cycling of bilirubin are the suggested causes of bilirubin stone formation. Bilirubin stones, often referred to as pigment stones, are seen primarily in patients with infections of the biliary tract or chronic hemolytic diseases (or damaged RBCs). […]

• #32 Gallbladder Stones – Pathogenesis and Treatment | IntechOpen

  https://www.intechopen.com/chapters/1147362

  Cholesterol gallstones cannot form if the gallbladder is completely emptied several times a day. Therefore, gallbladder dysmotility seems to be an important factor for cholelithiasis. Gallbladder dysmotility may be attributed to decreased sensitivity of the gallbladder to CCK. It has been observed that ICLCs density is markedly reduced in the gallbladder with stones. The reduced density of ICLCs decreases the gallbladder motility. […] The mechanism of gallstone formation amongst the various types of gallstones are mentioned below. […] The bile is concentrated 34 folds in the gallbladder due to water absorption and progressively increasing cholesterol in the micelle due to the preferential solubilization of bile salts with phospholipids leaving supersaturated bile cause cholesterol nucleation and this explains why the gallstones are usually seen in gallbladder than anywhere else in the biliary tree. […] Gallbladder dysmotility is another important factor for the development of cholesterol nucleation, since it causes stagnation of bile leading to crystal aggregation.

• #33 Management of Gallstones and Their Complications | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0315/p1673.html

  Gallstones found in the gallbladder are classified as cholesterol, pigmented or mixed stones, based on their chemical composition. Up to 90 percent of gallstones are cholesterol (more than 50 percent cholesterol) or mixed (20 to 50 percent cholesterol) gallstones. The remaining 10 percent of gallstones are pigmented stones, which have less than 20 percent cholesterol. […] The basic mechanism underlying the formation of gallstones is supersaturation, with constituents in bile exceeding their maximum solubilities. Additional factors contributing to gallstone formation are nucleation factors, bile stasis within the gallbladder and calcium in bile. Biliary cholesterol usually exists in a soluble single phase as micellar cholesterol. As the cholesterol concentration increases, cholesterol crystals begin to form.

• #34 Classification and pathogenesis of pigment gallstones | SpringerLink

  https://link.springer.com/chapter/10.1007/978-94-009-5606-3_10

  Pigment gallstones contain a variety of insoluble calcium salts. Calcium bilirubinate is usually the major component while cholesterol accounts for less than 50% by weight. The pathogenesis of each is conjectural. […] Black stones have a glass-like featureless appearance on fracturing. […] Brown stones are associated with stasis, bacterial infection and parasites, whereas black stones are found in sterile bile. […] Thus, aside from being pigmented and containing calcium bilirubinate, there are no common features in the pathogenesis of black and brown pigment stones, and they form in mutually exclusive circumstances. […] The epidemiological data presently available support the hypothesis that the conditions under which pigment stones form are not only separate from those for cholesterol stones but prevent the simultaneous formation of cholesterol stones. Similarly the conditions for formation of the two subtypes of pigment stones black and brown stones preclude simultaneous formation of the other.

• #35 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  There are three types of gallstones; first and most common type is cholesterol stone. Black and brown pigmented stones are the other two types of gallstones. The prevalence of various types of gallstones in the western world is: 75% of gallstones are cholesterol stones, 20% are black pigment stones, and 5% or less are brown pigment stones. Cholesterol and black pigment stones are formed exclusively in gallbladder in a sterile medium, while as brown pigment stones are formed everywhere in the biliary tree owing to the anaerobic bacterial infection. Stasis of bile is an essential component in the formation of gallstone or bile duct stone formation. […] Physical-chemical origin is the basis of pathogenesis of sterile stones (cholesterol and black pigment stones). There is an alteration in lipid and lipo-pigment composition which results in the formation of stones. In cholesterol and black pigment stones the major component is cholesterol monohydrate crystals and calcium hydrogen bilirubinate respectively. During the long stay in gallbladder, the black pigment gets degraded and polymerized by free radicals and helps in the formation of black pigment stones while as in the brown pigment stones the main mechanism is infectious where the enzymatic hydrolysis of biliary lipids by anaerobic bacterial enzymes produces supersaturated long chain fatty and deconjugated bile acids.

• #36 Classification and pathogenesis of pigment gallstones | SpringerLink

  https://link.springer.com/chapter/10.1007/978-94-009-5606-3_10

  Pigment gallstones contain a variety of insoluble calcium salts. Calcium bilirubinate is usually the major component while cholesterol accounts for less than 50% by weight. The pathogenesis of each is conjectural. […] Black stones have a glass-like featureless appearance on fracturing. […] Brown stones are associated with stasis, bacterial infection and parasites, whereas black stones are found in sterile bile. […] Thus, aside from being pigmented and containing calcium bilirubinate, there are no common features in the pathogenesis of black and brown pigment stones, and they form in mutually exclusive circumstances. […] The epidemiological data presently available support the hypothesis that the conditions under which pigment stones form are not only separate from those for cholesterol stones but prevent the simultaneous formation of cholesterol stones. Similarly the conditions for formation of the two subtypes of pigment stones black and brown stones preclude simultaneous formation of the other.

• #37 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  There are three types of gallstones; first and most common type is cholesterol stone. Black and brown pigmented stones are the other two types of gallstones. The prevalence of various types of gallstones in the western world is: 75% of gallstones are cholesterol stones, 20% are black pigment stones, and 5% or less are brown pigment stones. Cholesterol and black pigment stones are formed exclusively in gallbladder in a sterile medium, while as brown pigment stones are formed everywhere in the biliary tree owing to the anaerobic bacterial infection. Stasis of bile is an essential component in the formation of gallstone or bile duct stone formation. […] Physical-chemical origin is the basis of pathogenesis of sterile stones (cholesterol and black pigment stones). There is an alteration in lipid and lipo-pigment composition which results in the formation of stones. In cholesterol and black pigment stones the major component is cholesterol monohydrate crystals and calcium hydrogen bilirubinate respectively. During the long stay in gallbladder, the black pigment gets degraded and polymerized by free radicals and helps in the formation of black pigment stones while as in the brown pigment stones the main mechanism is infectious where the enzymatic hydrolysis of biliary lipids by anaerobic bacterial enzymes produces supersaturated long chain fatty and deconjugated bile acids.

• #38 Pathogenesis of gallstones – PubMed

  https://pubmed.ncbi.nlm.nih.gov/8480873/

  Gallstones form as a result of many disorders. Unphysiologic supersaturation, generally from hypersecretion of cholesterol, is essential for the formation of cholesterol gallstones. […] The other common abnormalities of the hepatobiliary system in gallstone patients are accelerated nucleation, gallbladder hypomotility, and the accumulation of mucin gel. […] Supersaturation of bile with calcium hydrogen bilirubinate, the acid calcium salt of unconjugated bilirubin, is essential for pigment gallstone formation, but its magnitude remains undefined in model systems. […] Nucleation and the precipitation of calcium hydrogen bilirubinate with the polymerization of the pigment in the gallbladder, together with the deposition of the inorganic salts, calcium carbonate and phosphate, result in black pigment gallstone formation.

• #39 Pathogenesis of gallstones – PubMed

  https://pubmed.ncbi.nlm.nih.gov/8480873/

  On the basis of ex vivo muscle studies, gallbladder hypomotility is unlikely in patients with black pigment stones but is invariably present in patients with cholesterol stones. […] Pigment supersaturation in the gallbladder is the result of hepatic hypersecretion of bilirubin conjugates in hemolytic disorders and possibly enterohepatic cycling of unconjugated bilirubin in nonhemolytic states. […] Less common is bile salt hyposecretion from impaired synthesis in constitutional disorders and cirrhosis, and uncompensated interruption of the enterohepatic circulation in ileal dysfunction syndromes. […] Bile salt deficiency causes incomplete solubilization of unconjugated bilirubin and impaired binding of calcium ions. […] Stasis and anaerobic bacterial infection are responsible for brown pigment stones, which usually form in the bile ducts. […] In addition to the precipitation of calcium hydrogen bilirubinate that remains unpolymerized, there is also the deposition of the calcium salts of saturated fatty acids and free bile acids, both of which are the result of bacterial enzymatic hydrolysis of biliary lipids.

• #40 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  Various defects occur simultaneously for the nucleation and crystallization of cholesterol monohydrate viz unphysiological supersaturation with cholesterol, accelerated nucleation and gallbladder hypomotility. The mucin glycoprotein hypersecretion follows and lead to the stone formation. Excessive secretion of cholesterol into bile leads to cholesterol supersaturation owing to multiple biochemical defects either from increased input (de novo synthesis, lipoprotein uptake) or decreased disposition (de novo bile salt and cholesteryl ester synthesis). […] Black stones occur in sterile environment with increased frequency in patients of chronic haemolysis. A shift in ratio of bilirubin diconjugates to the favour of monoconjugates especially monoglucuronides occur due to hypersecretion of bilirubin conjugates in bile. Bile pigment output increases by 10-fold with haemolysis and predominantly becomes monoconjugates that are more hydrolysed by endogenous glucuronidase.

• #41 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  Various defects occur simultaneously for the nucleation and crystallization of cholesterol monohydrate viz unphysiological supersaturation with cholesterol, accelerated nucleation and gallbladder hypomotility. The mucin glycoprotein hypersecretion follows and lead to the stone formation. Excessive secretion of cholesterol into bile leads to cholesterol supersaturation owing to multiple biochemical defects either from increased input (de novo synthesis, lipoprotein uptake) or decreased disposition (de novo bile salt and cholesteryl ester synthesis). […] Black stones occur in sterile environment with increased frequency in patients of chronic haemolysis. A shift in ratio of bilirubin diconjugates to the favour of monoconjugates especially monoglucuronides occur due to hypersecretion of bilirubin conjugates in bile. Bile pigment output increases by 10-fold with haemolysis and predominantly becomes monoconjugates that are more hydrolysed by endogenous glucuronidase.

• #42 Pathogenesis of gallstones – PubMed

  https://pubmed.ncbi.nlm.nih.gov/8480873/

  Gallstones form as a result of many disorders. Unphysiologic supersaturation, generally from hypersecretion of cholesterol, is essential for the formation of cholesterol gallstones. […] The other common abnormalities of the hepatobiliary system in gallstone patients are accelerated nucleation, gallbladder hypomotility, and the accumulation of mucin gel. […] Supersaturation of bile with calcium hydrogen bilirubinate, the acid calcium salt of unconjugated bilirubin, is essential for pigment gallstone formation, but its magnitude remains undefined in model systems. […] Nucleation and the precipitation of calcium hydrogen bilirubinate with the polymerization of the pigment in the gallbladder, together with the deposition of the inorganic salts, calcium carbonate and phosphate, result in black pigment gallstone formation.

• #43 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  There are three types of gallstones; first and most common type is cholesterol stone. Black and brown pigmented stones are the other two types of gallstones. The prevalence of various types of gallstones in the western world is: 75% of gallstones are cholesterol stones, 20% are black pigment stones, and 5% or less are brown pigment stones. Cholesterol and black pigment stones are formed exclusively in gallbladder in a sterile medium, while as brown pigment stones are formed everywhere in the biliary tree owing to the anaerobic bacterial infection. Stasis of bile is an essential component in the formation of gallstone or bile duct stone formation. […] Physical-chemical origin is the basis of pathogenesis of sterile stones (cholesterol and black pigment stones). There is an alteration in lipid and lipo-pigment composition which results in the formation of stones. In cholesterol and black pigment stones the major component is cholesterol monohydrate crystals and calcium hydrogen bilirubinate respectively. During the long stay in gallbladder, the black pigment gets degraded and polymerized by free radicals and helps in the formation of black pigment stones while as in the brown pigment stones the main mechanism is infectious where the enzymatic hydrolysis of biliary lipids by anaerobic bacterial enzymes produces supersaturated long chain fatty and deconjugated bile acids.

• #44 Pathogenesis of gallstones – PubMed

  https://pubmed.ncbi.nlm.nih.gov/8480873/

  On the basis of ex vivo muscle studies, gallbladder hypomotility is unlikely in patients with black pigment stones but is invariably present in patients with cholesterol stones. […] Pigment supersaturation in the gallbladder is the result of hepatic hypersecretion of bilirubin conjugates in hemolytic disorders and possibly enterohepatic cycling of unconjugated bilirubin in nonhemolytic states. […] Less common is bile salt hyposecretion from impaired synthesis in constitutional disorders and cirrhosis, and uncompensated interruption of the enterohepatic circulation in ileal dysfunction syndromes. […] Bile salt deficiency causes incomplete solubilization of unconjugated bilirubin and impaired binding of calcium ions. […] Stasis and anaerobic bacterial infection are responsible for brown pigment stones, which usually form in the bile ducts. […] In addition to the precipitation of calcium hydrogen bilirubinate that remains unpolymerized, there is also the deposition of the calcium salts of saturated fatty acids and free bile acids, both of which are the result of bacterial enzymatic hydrolysis of biliary lipids.

• #45 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  Chronic anaerobic infection with functional stasis of bile ducts is necessary for brown pigment stones. Stasis in bile duct occur due to secondary stones from gallbladder, or due to sphincter of Oddi dysfunction or parasitic infections. Commencing with stasis of bile and then followed by anaerobic bacterial infection lead to accumulation of both mucin gel and bacterial cytoskeleton in bile ducts.

• #46 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  Chronic anaerobic infection with functional stasis of bile ducts is necessary for brown pigment stones. Stasis in bile duct occur due to secondary stones from gallbladder, or due to sphincter of Oddi dysfunction or parasitic infections. Commencing with stasis of bile and then followed by anaerobic bacterial infection lead to accumulation of both mucin gel and bacterial cytoskeleton in bile ducts.

• #47 Pathophysiology of Gallstones | IntechOpen

  https://www.intechopen.com/chapters/79566

  Chronic anaerobic infection with functional stasis of bile ducts is necessary for brown pigment stones. Stasis in bile duct occur due to secondary stones from gallbladder, or due to sphincter of Oddi dysfunction or parasitic infections. Commencing with stasis of bile and then followed by anaerobic bacterial infection lead to accumulation of both mucin gel and bacterial cytoskeleton in bile ducts.

• #48 Pathogenesis of gallstones – PubMed

  https://pubmed.ncbi.nlm.nih.gov/8480873/

  On the basis of ex vivo muscle studies, gallbladder hypomotility is unlikely in patients with black pigment stones but is invariably present in patients with cholesterol stones. […] Pigment supersaturation in the gallbladder is the result of hepatic hypersecretion of bilirubin conjugates in hemolytic disorders and possibly enterohepatic cycling of unconjugated bilirubin in nonhemolytic states. […] Less common is bile salt hyposecretion from impaired synthesis in constitutional disorders and cirrhosis, and uncompensated interruption of the enterohepatic circulation in ileal dysfunction syndromes. […] Bile salt deficiency causes incomplete solubilization of unconjugated bilirubin and impaired binding of calcium ions. […] Stasis and anaerobic bacterial infection are responsible for brown pigment stones, which usually form in the bile ducts. […] In addition to the precipitation of calcium hydrogen bilirubinate that remains unpolymerized, there is also the deposition of the calcium salts of saturated fatty acids and free bile acids, both of which are the result of bacterial enzymatic hydrolysis of biliary lipids.

• #49 Mechanism of gallstone formation – biocrates life sciences ag

  https://biocrates.com/mechanism-of-gallstone-formation/

  Gallstones are the most prevalent disease of the gallbladder and one of the leading causes of hospitalization worldwide. If the limit of solubilization capacity of the bile is reached, precipitation of bile components like cholesterol and calcium salts to crystals occurs. However, the factors and mechanism leading to the aggregation of these precipitations to larger gallstones are still not completely understood. […] Prof. Martin Herrmann and his team from the University Hospital Erlangen in Germany revealed that chromatin, externalized by certain immune cells, plays a role in the aggregation of bile precipitations to gallstones. Analysis of gallstones showed the presence of neutrophil-derived enzymes and extracellular DNA, indicating the interaction of gallstone components and neutrophil extracellular traps (NETs). The shell-like structure of gallstones suggests episodic growth, where calcium and cholesterol crystals aggregate during NET formation. Based on the fact that macropinocytosis is a key mechanism of NET formation, crystal uptake could be shown to cause lysosomal leakage, which results in decondensation and externalization of neutrophil DNA.

• #50 Mechanism of gallstone formation – biocrates life sciences ag

  https://biocrates.com/mechanism-of-gallstone-formation/

  Gallstones are the most prevalent disease of the gallbladder and one of the leading causes of hospitalization worldwide. If the limit of solubilization capacity of the bile is reached, precipitation of bile components like cholesterol and calcium salts to crystals occurs. However, the factors and mechanism leading to the aggregation of these precipitations to larger gallstones are still not completely understood. […] Prof. Martin Herrmann and his team from the University Hospital Erlangen in Germany revealed that chromatin, externalized by certain immune cells, plays a role in the aggregation of bile precipitations to gallstones. Analysis of gallstones showed the presence of neutrophil-derived enzymes and extracellular DNA, indicating the interaction of gallstone components and neutrophil extracellular traps (NETs). The shell-like structure of gallstones suggests episodic growth, where calcium and cholesterol crystals aggregate during NET formation. Based on the fact that macropinocytosis is a key mechanism of NET formation, crystal uptake could be shown to cause lysosomal leakage, which results in decondensation and externalization of neutrophil DNA.

• #51 Mechanism of gallstone formation – biocrates life sciences ag

  https://biocrates.com/mechanism-of-gallstone-formation/

  Gallstones are the most prevalent disease of the gallbladder and one of the leading causes of hospitalization worldwide. If the limit of solubilization capacity of the bile is reached, precipitation of bile components like cholesterol and calcium salts to crystals occurs. However, the factors and mechanism leading to the aggregation of these precipitations to larger gallstones are still not completely understood. […] Prof. Martin Herrmann and his team from the University Hospital Erlangen in Germany revealed that chromatin, externalized by certain immune cells, plays a role in the aggregation of bile precipitations to gallstones. Analysis of gallstones showed the presence of neutrophil-derived enzymes and extracellular DNA, indicating the interaction of gallstone components and neutrophil extracellular traps (NETs). The shell-like structure of gallstones suggests episodic growth, where calcium and cholesterol crystals aggregate during NET formation. Based on the fact that macropinocytosis is a key mechanism of NET formation, crystal uptake could be shown to cause lysosomal leakage, which results in decondensation and externalization of neutrophil DNA.

• #52 Mechanism of gallstone formation – biocrates life sciences ag

  https://biocrates.com/mechanism-of-gallstone-formation/

  Gallstones are the most prevalent disease of the gallbladder and one of the leading causes of hospitalization worldwide. If the limit of solubilization capacity of the bile is reached, precipitation of bile components like cholesterol and calcium salts to crystals occurs. However, the factors and mechanism leading to the aggregation of these precipitations to larger gallstones are still not completely understood. […] Prof. Martin Herrmann and his team from the University Hospital Erlangen in Germany revealed that chromatin, externalized by certain immune cells, plays a role in the aggregation of bile precipitations to gallstones. Analysis of gallstones showed the presence of neutrophil-derived enzymes and extracellular DNA, indicating the interaction of gallstone components and neutrophil extracellular traps (NETs). The shell-like structure of gallstones suggests episodic growth, where calcium and cholesterol crystals aggregate during NET formation. Based on the fact that macropinocytosis is a key mechanism of NET formation, crystal uptake could be shown to cause lysosomal leakage, which results in decondensation and externalization of neutrophil DNA.

• #53 Mechanism of gallstone formation – biocrates life sciences ag

  https://biocrates.com/mechanism-of-gallstone-formation/

  Furthermore, in vivo experiments in mice showed that deficiency in neutrophil activity and chromatin decondensation impairs the development of gallstones, while the bile composition was not affected. Importantly, pharmacological targeting of neutrophil activity or NET formation by small molecules blocked gallstone formation and growth. This study provides profound evidence that gallstone development can be reduced through pharmacological interference with neutrophils and the corresponding NET formation. The findings pave the way for promising therapeutic approaches to prevent gallstone formation and growth.

• #54 Mechanism of gallstone formation – biocrates life sciences ag

  https://biocrates.com/mechanism-of-gallstone-formation/

  Furthermore, in vivo experiments in mice showed that deficiency in neutrophil activity and chromatin decondensation impairs the development of gallstones, while the bile composition was not affected. Importantly, pharmacological targeting of neutrophil activity or NET formation by small molecules blocked gallstone formation and growth. This study provides profound evidence that gallstone development can be reduced through pharmacological interference with neutrophils and the corresponding NET formation. The findings pave the way for promising therapeutic approaches to prevent gallstone formation and growth.

• #55 Unlocking the secrets of gallstones | FAU Erlangen-Nürnberg

  https://www.fau.eu/2019/10/news/research/unlocking-the-secrets-of-gallstones/

  Mechanism for the formation of gallstones has been discovered. […] The mechanism behind this process has now been discovered. […] All gallstones are covered with the traces of a special type of white blood cell called neutrophil granulocytes. […] We observed that the nets, when released in the already sticky bile, clumped together calcium and cholesterol crystals to form gallstones. […] The production of gallstones can be greatly reduced or even stopped if the formation of these nets is inhibited using drugs, says Dr. Munoz. […] Metoprolol prevents neutrophil granulocytes from entering tissue from the blood supply, thus reducing the capacity for forming nets and therefore gallstones. […] Specific inhibitors for preventing the formation of nets from neutrophil granulocytes, so-called PAD inhibitors, are already known that can inhibit the formation of gallstones produced in experiments, thus proving the significance of the immune system for the formation of these structures. […] This process is significant not only for gallstones, but also for other types of stones in the body such as kidney stones or salivary stones.

• #56 Unlocking the secrets of gallstones | FAU Erlangen-Nürnberg

  https://www.fau.eu/2019/10/news/research/unlocking-the-secrets-of-gallstones/

  Mechanism for the formation of gallstones has been discovered. […] The mechanism behind this process has now been discovered. […] All gallstones are covered with the traces of a special type of white blood cell called neutrophil granulocytes. […] We observed that the nets, when released in the already sticky bile, clumped together calcium and cholesterol crystals to form gallstones. […] The production of gallstones can be greatly reduced or even stopped if the formation of these nets is inhibited using drugs, says Dr. Munoz. […] Metoprolol prevents neutrophil granulocytes from entering tissue from the blood supply, thus reducing the capacity for forming nets and therefore gallstones. […] Specific inhibitors for preventing the formation of nets from neutrophil granulocytes, so-called PAD inhibitors, are already known that can inhibit the formation of gallstones produced in experiments, thus proving the significance of the immune system for the formation of these structures. […] This process is significant not only for gallstones, but also for other types of stones in the body such as kidney stones or salivary stones.

• #57 Gallstone Disease and Microbiome

  https://www.mdpi.com/2076-2607/8/6/835

  Gallstone disease (GSD) has, for many years, remained a high-cost, socially significant public health problem. Over the past decade, a number of studies have been carried out—both in humans and in animal models—confirming the role of the microbiota in various sections of the gastrointestinal tract as a new link in the etiopathogenesis of GSD. […] The presence of H. pylori infection contributes to the formation of gallstones and affects the occurrence of complications of GSD, including acute and chronic cholecystitis, cholangitis, pancreatitis. […] The microbiota is involved in the regulation of hydrolysis of bile acids to constituent components, cleavage of exogenous aromatic rings, deconjugation of bile acid complexes by hydrolytic enzymes, and the formation of free bile acids. […] The gut microbiota-mediated biotransformation of the bile acid pool regulates bile acids signaling by affecting the activation of host bile acids receptors such as nuclear receptor farnesoid X receptor (FXR), which governs bile, glucose and lipid metabolism.

• #58 The role of bacteria in gallstone pathogenesis

  https://www.imrpress.com/journal/FBL/6/4/10.2741/swidsinski

  Bacteria are often found in high concentrations in brown pigment and less so in cholesterol gallstones. […] Although it is intriguing to hypothesize that cholesterol stone formation is non-bacterial in nature and principally different from the pathogenesis of „infectious” brown pigment gallstones, it is more likely that significant overlap exists between the two processes. […] Most gallstones are composite in nature. […] Using molecular-genetic methods, bacteria can be found in most pure cholesterol gallstones (i.e. those whose structure consists of more than 90% cholesterol). […] The natural history of the gallstones development is unknown. […] It is likely that brown pigment stones can evolve in their chemical composition after the termination of the infectious process that initiate their formation, and may further develop into either mixed or nearly pure cholesterol stones.

• #59 Gallstone Disease and Microbiome

  https://www.mdpi.com/2076-2607/8/6/835

  Gallstone disease (GSD) has, for many years, remained a high-cost, socially significant public health problem. Over the past decade, a number of studies have been carried out—both in humans and in animal models—confirming the role of the microbiota in various sections of the gastrointestinal tract as a new link in the etiopathogenesis of GSD. […] The presence of H. pylori infection contributes to the formation of gallstones and affects the occurrence of complications of GSD, including acute and chronic cholecystitis, cholangitis, pancreatitis. […] The microbiota is involved in the regulation of hydrolysis of bile acids to constituent components, cleavage of exogenous aromatic rings, deconjugation of bile acid complexes by hydrolytic enzymes, and the formation of free bile acids. […] The gut microbiota-mediated biotransformation of the bile acid pool regulates bile acids signaling by affecting the activation of host bile acids receptors such as nuclear receptor farnesoid X receptor (FXR), which governs bile, glucose and lipid metabolism.

• #60 Gallstone Disease and Microbiome

  https://www.mdpi.com/2076-2607/8/6/835

  Gallstone disease (GSD) has, for many years, remained a high-cost, socially significant public health problem. Over the past decade, a number of studies have been carried out—both in humans and in animal models—confirming the role of the microbiota in various sections of the gastrointestinal tract as a new link in the etiopathogenesis of GSD. […] The presence of H. pylori infection contributes to the formation of gallstones and affects the occurrence of complications of GSD, including acute and chronic cholecystitis, cholangitis, pancreatitis. […] The microbiota is involved in the regulation of hydrolysis of bile acids to constituent components, cleavage of exogenous aromatic rings, deconjugation of bile acid complexes by hydrolytic enzymes, and the formation of free bile acids. […] The gut microbiota-mediated biotransformation of the bile acid pool regulates bile acids signaling by affecting the activation of host bile acids receptors such as nuclear receptor farnesoid X receptor (FXR), which governs bile, glucose and lipid metabolism.

• #61 Gallstone Disease and Microbiome

  https://www.mdpi.com/2076-2607/8/6/835

  Each factor that disrupts enterohepatic circulation leads to the formation of gallstones. […] The biliary tract microbiota is actively involved in mechanisms that ensure the prevention of colonization of the biliary tract by exogenous microorganisms and their immunological tolerance. […] Studies are being conducted with the aim of determining the possibility of using the evaluation of the composition of the microbiota of the gallbladder as an early diagnostic marker of gallstone formation.

• #62 Gallstone Disease and Microbiome

  https://www.mdpi.com/2076-2607/8/6/835

  Each factor that disrupts enterohepatic circulation leads to the formation of gallstones. […] The biliary tract microbiota is actively involved in mechanisms that ensure the prevention of colonization of the biliary tract by exogenous microorganisms and their immunological tolerance. […] Studies are being conducted with the aim of determining the possibility of using the evaluation of the composition of the microbiota of the gallbladder as an early diagnostic marker of gallstone formation.

• #63 Gallstone pathogenesis

  https://www.jstage.jst.go.jp/article/tando1987/21/2/21_153/_article/

  Gallstone pathogenesis is highly multi-factorial, resulting from complex interactions that involve environmental factors, dietary factors, metabolic disturbances, and genetic susceptibility. […] Cholesterol gallstones are associated with obesity, hyperlipidemias, middle-aged female gender, whereas such determinants are less associated with pigment gallstones. […] Because of the etiological difference, clinical differentiation of stone types is crucial in clarifying the reliable determinants of causal association between risk factors and gallstone diseases.

• #64 Gallstone – Wikipedia

  https://en.wikipedia.org/wiki/Gallstone

  Cholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. […] The first is how often and how well the gallbladder contracts; incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation. […] The second factor is the presence of proteins in the liver and bile that either promote or inhibit cholesterol crystallization into gallstones. […] In addition, increased levels of the hormone estrogen, as a result of pregnancy or hormone therapy, or the use of combined (estrogen-containing) forms of hormonal contraception, may increase cholesterol levels in bile and also decrease gallbladder motility, resulting in gallstone formation.

• #65 Factors Influencing Gallstone Formation: A Review of the Literature

  https://www.mdpi.com/2218-273X/12/4/550

  Additionally, the formation of gallstones is related to factors such as age, gender, weight, and bacterial infection. […] This review describes and summarizes the causes, formation process and influencing factors of gallstones, and discusses potential mechanisms for their formation. […] The pathogenesis of cholesterol gallstone disease is precipitated by: genetic factors; excessive cholesterol secretion by the liver (leading to supersaturation of cholesterol in gallbladder bile); rapid phase change by accelerating the growth of cholesterol crystals and solid cholesterol crystals; impairment of gallbladder motility; and intestinal factors. […] These factors will increase the production or growth of cholesterol crystals, eventually leading to the formation of stones. […] Cholesterol is a major component of most gallstones and is a major component of atherosclerotic plaques.

• #66 Pathogenesis of gallstones

  http://www.annclinlabsci.org/content/14/4/243.short?related-urls=yes&legid=acls;14/4/243

  The three lipids in bile, cholesterol, lecithin, and bile salts (about 90 percent of the dry weight of normal gallbladder bile) are amphipathic substances having both hydrophobic and hydrophilic functional groups. Knowledge of the physicochemical factors of gallstone formation (especially cholesterol stones) has increased in the past two decades. The absolute amount of cholesterol supersaturation determines the extent of cholesterol precipitation. The ionic strength of the bile and the types of bile salts present are minor factors, whereas the ratios of bile salts to lecithin at a particular concentration of total lipids are the major factors contributing to gallstone production. […] Additional important risk factors are genetic and ethnic, sex (females predominate), obesity, diet (in contrast to animal protein and more refined carbohydrate diets, there is less lithogenicity with diets containing plant protein and unrefined carbohydrates), certain diseases, and drug therapy. Pigment stones make up the majority of radiopaque stones and are predominant in the Orient; they are seen in certain diseases and in infections of the biliary tree.

• #67 Pathogenesis, Diagnosis and Treatment of Gallstone Disease A Brief Review – International Research and Publishing Academy

  https://irapa.org/pathogenesis-diagnosis-and-treatment-of-gallstone-disease-a-brief-review/

  Gallstone disease is a gastrointestinal disease that results from the dysfunction of cholesterol, bile, and bilirubin metabolism. […] The pathogenesis of this disease is related to the interaction between genetic and environmental factors, which include hepatic cholesterol hypersecretion, bile supersaturation, mucin, inflammatory changes, intestinal hypomotility, intestinal cholesterol hyperabsorption, and gut microbe alterations. […] The major genetic factors of this disease are the mutations in the hepatic cholesterol transporter ABCC8 and the cholecystokinin a receptor gene.

• #68 Factors Influencing Gallstone Formation: A Review of the Literature

  https://www.mdpi.com/2218-273X/12/4/550

  Gallstone disease is a common pathology of the digestive system with nearly a 10–20% incidence rate among adults. […] Clinical research suggests that cholelithiasis is closely related to the age, gender, body mass index, and other basic physical characteristics of patients. […] Clinical research further suggests that the occurrence of cholelithiasis is related to obesity, diabetes, non-alcoholic fatty liver, and other diseases. […] Herein, we summarize and analyze the causes and mechanisms of cholelithiasis, discuss its correlation with the pathogenesis of related diseases, and discuss possible mechanisms. […] In 2010, five factors were proposed to promote the formation of gallstones. These include genetic factors; excessive liver cholesterol secretion (resulting in cholesterol supersaturation in gallbladder bile); factors that accelerate the growth of cholesterol crystals and solid cholesterol crystals; impairment of gallbladder motility; and intestinal factors.

• #69 The association between gallstones and metabolic syndrome in urban Han Chinese: a longitudinal cohort study | Scientific Reports

  https://www.nature.com/articles/srep29937

  We carried out a gender-specific study to research the relationship between MetS and gallstone. […] MetS was significantly associated with gallstone in all participants. […] The same relationship between MetS and gallstone was observed in males, but there was no statistical evidence about this association in females. […] The results were as follows: Obesity is not only a symptom but also a disorder which is a major factor in MetS. […] We also discovered that obesity had significant relationship with the development of gallstones, supported by previous studies. […] This study illustrated that, there was a strong association between diabetes mellitus with gallstone events which was consistence with previous studies. […] In this observational study, there was a positive relationship with high blood pressure and developing gallstones which was concordant with a study implemented in Taiwan, China.

• #70 The association between gallstones and metabolic syndrome in urban Han Chinese: a longitudinal cohort study | Scientific Reports

  https://www.nature.com/articles/srep29937

  We carried out a gender-specific study to research the relationship between MetS and gallstone. […] MetS was significantly associated with gallstone in all participants. […] The same relationship between MetS and gallstone was observed in males, but there was no statistical evidence about this association in females. […] The results were as follows: Obesity is not only a symptom but also a disorder which is a major factor in MetS. […] We also discovered that obesity had significant relationship with the development of gallstones, supported by previous studies. […] This study illustrated that, there was a strong association between diabetes mellitus with gallstone events which was consistence with previous studies. […] In this observational study, there was a positive relationship with high blood pressure and developing gallstones which was concordant with a study implemented in Taiwan, China.

• #71 The association between gallstones and metabolic syndrome in urban Han Chinese: a longitudinal cohort study | Scientific Reports

  https://www.nature.com/articles/srep29937

  And the risk of gallstone disease increases with the number of components of MetS for males but not for females. […] In this large-scale longitudinal-cohort study, we aimed to shed light on the relationship between MetS and the development of gallstone events and evaluate whether count of metabolic abnormalities was associated with gallstones in target population. […] The relationship between MetS and gallstone disease had received much attention recently, but few studies had reported in Chinese population. […] We found the incidence density of gallstone event in the group with MetS was higher than the incidence density in the group without MetS. […] A significant association (RR=1.25, P=0.0097) was observed between MetS and gallstones development for all subjects in this 6 years follow-up study.

• #72 Gallstone pathogenesis

  https://www.jstage.jst.go.jp/article/tando1987/21/2/21_153/_article/

  Gallstone pathogenesis is highly multi-factorial, resulting from complex interactions that involve environmental factors, dietary factors, metabolic disturbances, and genetic susceptibility. […] Cholesterol gallstones are associated with obesity, hyperlipidemias, middle-aged female gender, whereas such determinants are less associated with pigment gallstones. […] Because of the etiological difference, clinical differentiation of stone types is crucial in clarifying the reliable determinants of causal association between risk factors and gallstone diseases.

• #73

  https://medium.com/@lydiabilodeau79/identify-the-etiology-pathogenesis-and-clinical-manifestations-of-gallstones-cholelithiasis-7ae6d3eafaae

  Gallstones, medically termed cholelithiasis, arise from imbalances in bile composition within the gallbladder, leading to the formation of solid particles. […] The etiology of gallstone formation involves a complex interplay of genetic predisposition, metabolic factors, and gallbladder motility abnormalities. […] The pathogenesis of gallstones is multifactorial. Conditions such as obesity, rapid weight loss, pregnancy, and certain metabolic disorders like diabetes mellitus predispose individuals to gallstone formation. These conditions alter cholesterol metabolism or bile composition, promoting stone formation. Gallbladder stasis, where bile stagnates due to decreased gallbladder emptying, further facilitates stone formation by concentrating bile constituents.

• #74 The role of dietary fats in the pathogenesis of gallstones

  https://www.imrpress.com/journal/fbl/8/5/10.2741/1110

  Gallstone disease is exceptionally common, occurring especially in Western populations, with cholesterol gallstones predominating. Currently, it is believed that one of the essential factors in the pathogenesis of cholesterol gallstones is a physical–chemical event that results primarily from alterations in the lipid composition of gallbladder bile. […] Cholesterol supersaturation is due principally to excessive secretion of cholesterol into the bile. Several biochemical defects, as well as diet, might cause hypersecretion of cholesterol. […] The precise effects of diet on cholesterol supersaturation of bile have not been clearly established, although epidemiological, clinical, and animal studies indicate that diet plays an important role in cholesterol gallstone formation. This review summarizes current information on the role of dietary fat in the modulation of cholesterol gallstone formation.

• #75 The role of dietary fats in the pathogenesis of gallstones

  https://www.imrpress.com/journal/fbl/8/5/10.2741/1110

  Gallstone disease is exceptionally common, occurring especially in Western populations, with cholesterol gallstones predominating. Currently, it is believed that one of the essential factors in the pathogenesis of cholesterol gallstones is a physical–chemical event that results primarily from alterations in the lipid composition of gallbladder bile. […] Cholesterol supersaturation is due principally to excessive secretion of cholesterol into the bile. Several biochemical defects, as well as diet, might cause hypersecretion of cholesterol. […] The precise effects of diet on cholesterol supersaturation of bile have not been clearly established, although epidemiological, clinical, and animal studies indicate that diet plays an important role in cholesterol gallstone formation. This review summarizes current information on the role of dietary fat in the modulation of cholesterol gallstone formation.

• #76 Pathogenesis of gallstones

  http://www.annclinlabsci.org/content/14/4/243.short?related-urls=yes&legid=acls;14/4/243

  The three lipids in bile, cholesterol, lecithin, and bile salts (about 90 percent of the dry weight of normal gallbladder bile) are amphipathic substances having both hydrophobic and hydrophilic functional groups. Knowledge of the physicochemical factors of gallstone formation (especially cholesterol stones) has increased in the past two decades. The absolute amount of cholesterol supersaturation determines the extent of cholesterol precipitation. The ionic strength of the bile and the types of bile salts present are minor factors, whereas the ratios of bile salts to lecithin at a particular concentration of total lipids are the major factors contributing to gallstone production. […] Additional important risk factors are genetic and ethnic, sex (females predominate), obesity, diet (in contrast to animal protein and more refined carbohydrate diets, there is less lithogenicity with diets containing plant protein and unrefined carbohydrates), certain diseases, and drug therapy. Pigment stones make up the majority of radiopaque stones and are predominant in the Orient; they are seen in certain diseases and in infections of the biliary tree.

• #77 Cholelithiasis – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/cholelithiasis/

  Cholelithiasis refers to the presence of abnormal concretions (gallstones) in the gallbladder. […] Gallstones most commonly consist of cholesterol but may be pigmented (due to hemolysis or infection) or mixed. […] Cholelithiasis can manifest with biliary colic (postprandial RUQ pain) but is most commonly an incidental finding in asymptomatic individuals. […] The diagnosis is confirmed by ultrasound. […] Mechanism: Bile cholesterol oversaturation, bile stasis, impaired bile acid circulation precipitation of gallstones in the gallbladder. […] Pathophysiology: abnormal hepatic cholesterol metabolism cholesterol concentration in bile and bile salts and lecithin hypersaturated bile precipitation of cholesterol and calcium carbonate cholesterol stones or mixed stones. […] During pregnancy, increased estrogen levels cause increased secretion of lithogenic bile (rich in cholesterol), resulting in the formation of cholesterol gallstones. Increased progesterone levels cause smooth muscle relaxation, decreased and impaired gallbladder contraction, and subsequent bile stasis and formation of gallstones.

• #78 Pathogenesis of gallstones

  http://www.annclinlabsci.org/content/14/4/243.short?related-urls=yes&legid=acls;14/4/243

  The three lipids in bile, cholesterol, lecithin, and bile salts (about 90 percent of the dry weight of normal gallbladder bile) are amphipathic substances having both hydrophobic and hydrophilic functional groups. Knowledge of the physicochemical factors of gallstone formation (especially cholesterol stones) has increased in the past two decades. The absolute amount of cholesterol supersaturation determines the extent of cholesterol precipitation. The ionic strength of the bile and the types of bile salts present are minor factors, whereas the ratios of bile salts to lecithin at a particular concentration of total lipids are the major factors contributing to gallstone production. […] Additional important risk factors are genetic and ethnic, sex (females predominate), obesity, diet (in contrast to animal protein and more refined carbohydrate diets, there is less lithogenicity with diets containing plant protein and unrefined carbohydrates), certain diseases, and drug therapy. Pigment stones make up the majority of radiopaque stones and are predominant in the Orient; they are seen in certain diseases and in infections of the biliary tree.

• #79 Cholelithiasis – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/gallbladder-and-bile-duct-disorders/cholelithiasis

  Biliary sludge is often a precursor of gallstones. It consists of calcium bilirubinate (a polymer of bilirubin), cholesterol microcrystals, and mucin. Sludge develops during gallbladder stasis, as occurs during pregnancy or use of total parenteral nutrition. Most sludge is asymptomatic and disappears when the primary condition resolves. Alternatively, sludge can evolve into gallstones or migrate into the biliary tract, obstructing the ducts and leading to biliary colic, cholangitis, or pancreatitis. […] Cholesterol stones account for 85% of gallstones in the Western world. For cholesterol gallstones to form, bile must be supersaturated with cholesterol. Normally, water-insoluble cholesterol is made water soluble by combining with bile salts and lecithin to form mixed micelles. Supersaturation of bile with cholesterol most commonly results from excessive cholesterol secretion but may result from a decrease in bile salt secretion or in lecithin secretion.

• #80 Pathogenesis of gall stones in Crohn’s disease: an alternative explanation. | Gut

  https://gut.bmj.com/content/35/1/94

  The increased prevalence of gall stones in Crohn’s disease is thought to be related to depletion of the bile salt pool due either to terminal ileal disease or after ileal resection. […] It is suggested that mechanisms other than ileal dysfunction may predispose to gall stones. Postoperative gall bladder hypomotility with biliary sludge formation may be precursors of gall stone formation in patients with Crohn’s disease.

• #81 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  The pathogenesis of cholecystitis most commonly involves the impaction of gallstones in the bladder neck, Hartmanns pouch, or the cystic duct; gallstones are not always present in cholecystitis, however. Pressure on the gallbladder increases, the organ becomes enlarged, the walls thicken, the blood supply decreases, and an exudate may form. Cholecystitis can be either acute or chronic, with repeated episodes of acute inflammation potentially leading to chronic cholecystitis. The gallbladder can become infected by various microorganisms, including those that are gas forming. An inflamed gallbladder can undergo necrosis and gangrene and, if left untreated, may progress to symptomatic sepsis. Failure to properly treat cholecystitis may result in perforation of the gallbladder, a rare but life-threatening phenomenon. Cholecystitis also can lead to gallstone pancreatitis if stones dislodge down to the sphincter of Oddi and are not cleared, thus blocking the pancreatic duct.

• #82 Gallstone-related pathogenesis of acute pancreatitis | Pancreapedia

  https://pancreapedia.org/reviews/gallstone-related-pathogenesis-of-acute-pancreatitis

  Acute pancreatitis is now the most common reason for hospital admission among all gastrointestinal disorders. In most countries the presence of gallbladder stones represents the most frequent and significant risk factors for developing acute pancreatitis and underlying gallstone disease accounts for between 30 and 50% of cases with pancreatitis. […] Acute Pancreatitis is an inflammatory disorder of the exocrine pancreas caused, in most cases, by immoderate alcohol consumption or the passage of gallstones. […] Once a patient has developed pancreatitis due to gallstones the disease is likely to recur if the source of migrating bile duct stones is not removed or their impaction at the duodenal papilla is not prevented. […] Taken together these clinical and population-based observations indicate that a) carrying gallstones increases the risk of developing acute pancreatitis; b) only gallstones that are small enough to pass through the biliary tract, rather than the ones that remain asymptomatically in the gallbladder, confer a pancreatitis risk; c) strategies intended to remove the source of migrating gallstone or that prevent their impaction near the duodenal papilla reduce the risk of developing pancreatitis in the first place and the risk of a recurrence of pancreatitis; and d) preserving the flow from the pancreatic duct is an effective way of preventing ERCP-induced pancreatitis, a clinical entity considered to be caused by obstruction of the pancreatic duct.

• #83 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  The pathogenesis of cholecystitis most commonly involves the impaction of gallstones in the bladder neck, Hartmanns pouch, or the cystic duct; gallstones are not always present in cholecystitis, however. Pressure on the gallbladder increases, the organ becomes enlarged, the walls thicken, the blood supply decreases, and an exudate may form. Cholecystitis can be either acute or chronic, with repeated episodes of acute inflammation potentially leading to chronic cholecystitis. The gallbladder can become infected by various microorganisms, including those that are gas forming. An inflamed gallbladder can undergo necrosis and gangrene and, if left untreated, may progress to symptomatic sepsis. Failure to properly treat cholecystitis may result in perforation of the gallbladder, a rare but life-threatening phenomenon. Cholecystitis also can lead to gallstone pancreatitis if stones dislodge down to the sphincter of Oddi and are not cleared, thus blocking the pancreatic duct.

• #84 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  The pathogenesis of cholecystitis most commonly involves the impaction of gallstones in the bladder neck, Hartmanns pouch, or the cystic duct; gallstones are not always present in cholecystitis, however. Pressure on the gallbladder increases, the organ becomes enlarged, the walls thicken, the blood supply decreases, and an exudate may form. Cholecystitis can be either acute or chronic, with repeated episodes of acute inflammation potentially leading to chronic cholecystitis. The gallbladder can become infected by various microorganisms, including those that are gas forming. An inflamed gallbladder can undergo necrosis and gangrene and, if left untreated, may progress to symptomatic sepsis. Failure to properly treat cholecystitis may result in perforation of the gallbladder, a rare but life-threatening phenomenon. Cholecystitis also can lead to gallstone pancreatitis if stones dislodge down to the sphincter of Oddi and are not cleared, thus blocking the pancreatic duct.

• #85 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  The pathogenesis of cholecystitis most commonly involves the impaction of gallstones in the bladder neck, Hartmanns pouch, or the cystic duct; gallstones are not always present in cholecystitis, however. Pressure on the gallbladder increases, the organ becomes enlarged, the walls thicken, the blood supply decreases, and an exudate may form. Cholecystitis can be either acute or chronic, with repeated episodes of acute inflammation potentially leading to chronic cholecystitis. The gallbladder can become infected by various microorganisms, including those that are gas forming. An inflamed gallbladder can undergo necrosis and gangrene and, if left untreated, may progress to symptomatic sepsis. Failure to properly treat cholecystitis may result in perforation of the gallbladder, a rare but life-threatening phenomenon. Cholecystitis also can lead to gallstone pancreatitis if stones dislodge down to the sphincter of Oddi and are not cleared, thus blocking the pancreatic duct.

• #86 Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment

  https://www.uspharmacist.com/article/gallbladder-disease-pathophysiology-diagnosis-and-treatment

  The pathogenesis of cholecystitis most commonly involves the impaction of gallstones in the bladder neck, Hartmanns pouch, or the cystic duct; gallstones are not always present in cholecystitis, however. Pressure on the gallbladder increases, the organ becomes enlarged, the walls thicken, the blood supply decreases, and an exudate may form. Cholecystitis can be either acute or chronic, with repeated episodes of acute inflammation potentially leading to chronic cholecystitis. The gallbladder can become infected by various microorganisms, including those that are gas forming. An inflamed gallbladder can undergo necrosis and gangrene and, if left untreated, may progress to symptomatic sepsis. Failure to properly treat cholecystitis may result in perforation of the gallbladder, a rare but life-threatening phenomenon. Cholecystitis also can lead to gallstone pancreatitis if stones dislodge down to the sphincter of Oddi and are not cleared, thus blocking the pancreatic duct.

• #87 Gallstone-related pathogenesis of acute pancreatitis | Pancreapedia

  https://pancreapedia.org/reviews/gallstone-related-pathogenesis-of-acute-pancreatitis

  Acute pancreatitis is now the most common reason for hospital admission among all gastrointestinal disorders. In most countries the presence of gallbladder stones represents the most frequent and significant risk factors for developing acute pancreatitis and underlying gallstone disease accounts for between 30 and 50% of cases with pancreatitis. […] Acute Pancreatitis is an inflammatory disorder of the exocrine pancreas caused, in most cases, by immoderate alcohol consumption or the passage of gallstones. […] Once a patient has developed pancreatitis due to gallstones the disease is likely to recur if the source of migrating bile duct stones is not removed or their impaction at the duodenal papilla is not prevented. […] Taken together these clinical and population-based observations indicate that a) carrying gallstones increases the risk of developing acute pancreatitis; b) only gallstones that are small enough to pass through the biliary tract, rather than the ones that remain asymptomatically in the gallbladder, confer a pancreatitis risk; c) strategies intended to remove the source of migrating gallstone or that prevent their impaction near the duodenal papilla reduce the risk of developing pancreatitis in the first place and the risk of a recurrence of pancreatitis; and d) preserving the flow from the pancreatic duct is an effective way of preventing ERCP-induced pancreatitis, a clinical entity considered to be caused by obstruction of the pancreatic duct.

• #88 Gallstone-related pathogenesis of acute pancreatitis | Pancreapedia

  https://pancreapedia.org/reviews/gallstone-related-pathogenesis-of-acute-pancreatitis

  Acute pancreatitis is now the most common reason for hospital admission among all gastrointestinal disorders. In most countries the presence of gallbladder stones represents the most frequent and significant risk factors for developing acute pancreatitis and underlying gallstone disease accounts for between 30 and 50% of cases with pancreatitis. […] Acute Pancreatitis is an inflammatory disorder of the exocrine pancreas caused, in most cases, by immoderate alcohol consumption or the passage of gallstones. […] Once a patient has developed pancreatitis due to gallstones the disease is likely to recur if the source of migrating bile duct stones is not removed or their impaction at the duodenal papilla is not prevented. […] Taken together these clinical and population-based observations indicate that a) carrying gallstones increases the risk of developing acute pancreatitis; b) only gallstones that are small enough to pass through the biliary tract, rather than the ones that remain asymptomatically in the gallbladder, confer a pancreatitis risk; c) strategies intended to remove the source of migrating gallstone or that prevent their impaction near the duodenal papilla reduce the risk of developing pancreatitis in the first place and the risk of a recurrence of pancreatitis; and d) preserving the flow from the pancreatic duct is an effective way of preventing ERCP-induced pancreatitis, a clinical entity considered to be caused by obstruction of the pancreatic duct.

• #89 Gallstone-related pathogenesis of acute pancreatitis | Pancreapedia

  https://pancreapedia.org/reviews/gallstone-related-pathogenesis-of-acute-pancreatitis

  It is firmly established today that the initiation of pancreatitis requires the passage of a gallstone from the gallbladder through the biliary tract and gallstones, that remain in the gallbladder will not cause pancreatitis. […] This initial duct obstruction hypothesis was somewhat forgotten when Opie published his second common channel hypothesis during the same year. […] Although Opies common channel hypothesis seems rational from a mechanistic point of view and has become one of the most popular theories in the field, considerable experimental and clinical evidence is incompatible with its assumptions. […] Taken together these data suggest that the initial pathophysiological events during the course of gallstone-induced pancreatitis affect acinar cells and are triggered, in accordance with Opies initial hypothesis, by obstruction or impairment of flow form the pancreatic duct.

• #90 Gallstone-related pathogenesis of acute pancreatitis | Pancreapedia

  https://pancreapedia.org/reviews/gallstone-related-pathogenesis-of-acute-pancreatitis

  It is firmly established today that the initiation of pancreatitis requires the passage of a gallstone from the gallbladder through the biliary tract and gallstones, that remain in the gallbladder will not cause pancreatitis. […] This initial duct obstruction hypothesis was somewhat forgotten when Opie published his second common channel hypothesis during the same year. […] Although Opies common channel hypothesis seems rational from a mechanistic point of view and has become one of the most popular theories in the field, considerable experimental and clinical evidence is incompatible with its assumptions. […] Taken together these data suggest that the initial pathophysiological events during the course of gallstone-induced pancreatitis affect acinar cells and are triggered, in accordance with Opies initial hypothesis, by obstruction or impairment of flow form the pancreatic duct.

• #91 Gallstone-related pathogenesis of acute pancreatitis | Pancreapedia

  https://pancreapedia.org/reviews/gallstone-related-pathogenesis-of-acute-pancreatitis

  It is firmly established today that the initiation of pancreatitis requires the passage of a gallstone from the gallbladder through the biliary tract and gallstones, that remain in the gallbladder will not cause pancreatitis. […] This initial duct obstruction hypothesis was somewhat forgotten when Opie published his second common channel hypothesis during the same year. […] Although Opies common channel hypothesis seems rational from a mechanistic point of view and has become one of the most popular theories in the field, considerable experimental and clinical evidence is incompatible with its assumptions. […] Taken together these data suggest that the initial pathophysiological events during the course of gallstone-induced pancreatitis affect acinar cells and are triggered, in accordance with Opies initial hypothesis, by obstruction or impairment of flow form the pancreatic duct.

• #92 Cholelithiasis – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/gallbladder-and-bile-duct-disorders/cholelithiasis

  Biliary sludge is often a precursor of gallstones. It consists of calcium bilirubinate (a polymer of bilirubin), cholesterol microcrystals, and mucin. Sludge develops during gallbladder stasis, as occurs during pregnancy or use of total parenteral nutrition. Most sludge is asymptomatic and disappears when the primary condition resolves. Alternatively, sludge can evolve into gallstones or migrate into the biliary tract, obstructing the ducts and leading to biliary colic, cholangitis, or pancreatitis. […] Cholesterol stones account for 85% of gallstones in the Western world. For cholesterol gallstones to form, bile must be supersaturated with cholesterol. Normally, water-insoluble cholesterol is made water soluble by combining with bile salts and lecithin to form mixed micelles. Supersaturation of bile with cholesterol most commonly results from excessive cholesterol secretion but may result from a decrease in bile salt secretion or in lecithin secretion.

• #93 Cholelithiasis – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/gallbladder-and-bile-duct-disorders/cholelithiasis

  Biliary sludge is often a precursor of gallstones. It consists of calcium bilirubinate (a polymer of bilirubin), cholesterol microcrystals, and mucin. Sludge develops during gallbladder stasis, as occurs during pregnancy or use of total parenteral nutrition. Most sludge is asymptomatic and disappears when the primary condition resolves. Alternatively, sludge can evolve into gallstones or migrate into the biliary tract, obstructing the ducts and leading to biliary colic, cholangitis, or pancreatitis. […] Cholesterol stones account for 85% of gallstones in the Western world. For cholesterol gallstones to form, bile must be supersaturated with cholesterol. Normally, water-insoluble cholesterol is made water soluble by combining with bile salts and lecithin to form mixed micelles. Supersaturation of bile with cholesterol most commonly results from excessive cholesterol secretion but may result from a decrease in bile salt secretion or in lecithin secretion.

• #94 Cholelithiasis – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/gallbladder-and-bile-duct-disorders/cholelithiasis

  Biliary sludge is often a precursor of gallstones. It consists of calcium bilirubinate (a polymer of bilirubin), cholesterol microcrystals, and mucin. Sludge develops during gallbladder stasis, as occurs during pregnancy or use of total parenteral nutrition. Most sludge is asymptomatic and disappears when the primary condition resolves. Alternatively, sludge can evolve into gallstones or migrate into the biliary tract, obstructing the ducts and leading to biliary colic, cholangitis, or pancreatitis. […] Cholesterol stones account for 85% of gallstones in the Western world. For cholesterol gallstones to form, bile must be supersaturated with cholesterol. Normally, water-insoluble cholesterol is made water soluble by combining with bile salts and lecithin to form mixed micelles. Supersaturation of bile with cholesterol most commonly results from excessive cholesterol secretion but may result from a decrease in bile salt secretion or in lecithin secretion.

• #95 Cholelithiasis – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/gallbladder-and-bile-duct-disorders/cholelithiasis

  Biliary sludge is often a precursor of gallstones. It consists of calcium bilirubinate (a polymer of bilirubin), cholesterol microcrystals, and mucin. Sludge develops during gallbladder stasis, as occurs during pregnancy or use of total parenteral nutrition. Most sludge is asymptomatic and disappears when the primary condition resolves. Alternatively, sludge can evolve into gallstones or migrate into the biliary tract, obstructing the ducts and leading to biliary colic, cholangitis, or pancreatitis. […] Cholesterol stones account for 85% of gallstones in the Western world. For cholesterol gallstones to form, bile must be supersaturated with cholesterol. Normally, water-insoluble cholesterol is made water soluble by combining with bile salts and lecithin to form mixed micelles. Supersaturation of bile with cholesterol most commonly results from excessive cholesterol secretion but may result from a decrease in bile salt secretion or in lecithin secretion.

• #96 Cholelithiasis – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/gallbladder-and-bile-duct-disorders/cholelithiasis

  Biliary sludge is often a precursor of gallstones. It consists of calcium bilirubinate (a polymer of bilirubin), cholesterol microcrystals, and mucin. Sludge develops during gallbladder stasis, as occurs during pregnancy or use of total parenteral nutrition. Most sludge is asymptomatic and disappears when the primary condition resolves. Alternatively, sludge can evolve into gallstones or migrate into the biliary tract, obstructing the ducts and leading to biliary colic, cholangitis, or pancreatitis. […] Cholesterol stones account for 85% of gallstones in the Western world. For cholesterol gallstones to form, bile must be supersaturated with cholesterol. Normally, water-insoluble cholesterol is made water soluble by combining with bile salts and lecithin to form mixed micelles. Supersaturation of bile with cholesterol most commonly results from excessive cholesterol secretion but may result from a decrease in bile salt secretion or in lecithin secretion.

• #97 Concept of the pathogenesis and treatment of cholelithiasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3295849/

  Gallstone disease (GD) is a chronic recurrent hepatobiliary disease, the basis for which is the impaired metabolism of cholesterol, bilirubin and bile acids, which is characterized by the formation of gallstones in the hepatic bile duct, common bile duct, or gallbladder. […] The pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental factors. […] Cholesterol GD results from a biochemical imbalance of lipids and bile salts in the gallbladder bile. […] The pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental factors. […] Cholesterol stones are formed in the gallbladder due to impaired relationships between the major bile components, cholesterol, phospholipids and bile acids.

• #98 Pathogenesis of gallstones – PubMed

  https://pubmed.ncbi.nlm.nih.gov/8480873/

  Gallstones form as a result of many disorders. Unphysiologic supersaturation, generally from hypersecretion of cholesterol, is essential for the formation of cholesterol gallstones. […] The other common abnormalities of the hepatobiliary system in gallstone patients are accelerated nucleation, gallbladder hypomotility, and the accumulation of mucin gel. […] Supersaturation of bile with calcium hydrogen bilirubinate, the acid calcium salt of unconjugated bilirubin, is essential for pigment gallstone formation, but its magnitude remains undefined in model systems. […] Nucleation and the precipitation of calcium hydrogen bilirubinate with the polymerization of the pigment in the gallbladder, together with the deposition of the inorganic salts, calcium carbonate and phosphate, result in black pigment gallstone formation.

• #99 Gallbladder Stones – Pathogenesis and Treatment | IntechOpen

  https://www.intechopen.com/chapters/1147362

  Gallstone disease (GSD) refers to all the patients with symptoms due to gallstones (cholelithiasis). […] There are several mechanism for cholelithiasis and all these processes are slow. Cholesterol stones are the most common variety of gallstones. Cholesterol stones cannot form if the gallbladder is completely emptied several times a day. Therefore, the total or partial extension of bile storage due to impaired gallbladder movement seems to be an important factor for cholelithiasis. Gallbladder dysmotility is an important risk factor for the development of GSD. […] The pathogenesis of gallstones are multifactorial including a variety of genetic and environmental factors. The local factors in the gall bladder include gallbladder dysmotility, hypersecretion and accumulation of mucin gel in the gall bladder lumen. The local factors in the bile consists of rapid phase transition of cholesterol from supersaturated hepatic bile and local immune mediated inflammation in the gallbladder.

• #100 Mechanism of gallstone formation – biocrates life sciences ag

  https://biocrates.com/mechanism-of-gallstone-formation/

  Gallstones are the most prevalent disease of the gallbladder and one of the leading causes of hospitalization worldwide. If the limit of solubilization capacity of the bile is reached, precipitation of bile components like cholesterol and calcium salts to crystals occurs. However, the factors and mechanism leading to the aggregation of these precipitations to larger gallstones are still not completely understood. […] Prof. Martin Herrmann and his team from the University Hospital Erlangen in Germany revealed that chromatin, externalized by certain immune cells, plays a role in the aggregation of bile precipitations to gallstones. Analysis of gallstones showed the presence of neutrophil-derived enzymes and extracellular DNA, indicating the interaction of gallstone components and neutrophil extracellular traps (NETs). The shell-like structure of gallstones suggests episodic growth, where calcium and cholesterol crystals aggregate during NET formation. Based on the fact that macropinocytosis is a key mechanism of NET formation, crystal uptake could be shown to cause lysosomal leakage, which results in decondensation and externalization of neutrophil DNA.

• #101 Gallstone Disease and Microbiome

  https://www.mdpi.com/2076-2607/8/6/835

  Gallstone disease (GSD) has, for many years, remained a high-cost, socially significant public health problem. Over the past decade, a number of studies have been carried out—both in humans and in animal models—confirming the role of the microbiota in various sections of the gastrointestinal tract as a new link in the etiopathogenesis of GSD. […] The presence of H. pylori infection contributes to the formation of gallstones and affects the occurrence of complications of GSD, including acute and chronic cholecystitis, cholangitis, pancreatitis. […] The microbiota is involved in the regulation of hydrolysis of bile acids to constituent components, cleavage of exogenous aromatic rings, deconjugation of bile acid complexes by hydrolytic enzymes, and the formation of free bile acids. […] The gut microbiota-mediated biotransformation of the bile acid pool regulates bile acids signaling by affecting the activation of host bile acids receptors such as nuclear receptor farnesoid X receptor (FXR), which governs bile, glucose and lipid metabolism.

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