Gallstone disease pathophysiology: Difference between revisions

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On the other hand, moderate intake of wine and the consumption of whole grain bread may decrease the risk of developing gallstones.
On the other hand, moderate intake of wine and the consumption of whole grain bread may decrease the risk of developing gallstones.
== Pathophysiology ==
== Pathophysiology ==
* The most common type of gallstone is a [[cholesterol]] stone.  
* The most common type of gallstone is a [[cholesterol]] stone.<ref name="pmid22570746">{{cite journal |vauthors=Stinton LM, Shaffer EA |title=Epidemiology of gallbladder disease: cholelithiasis and cancer |journal=Gut Liver |volume=6 |issue=2 |pages=172–87 |year=2012 |pmid=22570746 |pmc=3343155 |doi=10.5009/gnl.2012.6.2.172 |url=}}</ref><ref name="pmid12242178">{{cite journal |vauthors=Indar AA, Beckingham IJ |title=Acute cholecystitis |journal=BMJ |volume=325 |issue=7365 |pages=639–43 |year=2002 |pmid=12242178 |pmc=1124163 |doi= |url=}}</ref><ref>{{cite book | last = McPhee | first = Stephen | title = Pathophysiology of disease : an introduction to clinical medicine | publisher = McGraw-Hill Education Medical | location = New York | year = 2014 | isbn = 0071806008 }}</ref><ref name="pmid17981556">{{cite journal |vauthors=Wang HH, Portincasa P, Wang DQ |title=Molecular pathophysiology and physical chemistry of cholesterol gallstones |journal=Front. Biosci. |volume=13 |issue= |pages=401–23 |year=2008 |pmid=17981556 |doi= |url=}}</ref><ref>{{cite journal |year=1995 |month=June |title=. |journal=European Journal Gastroenterology & Hepatology |volume=6 |pages=585-593 |accessdate= 2007-08-25}}</ref>
* When pronucleating proteins are present, such as [[mucin]], the bile becomes [[Supersaturation|hypersaturated]] with [[cholesterol]] and [[cholesterol]] stones form.  
* When pronucleating proteins are present, such as [[mucin]], the bile becomes [[Supersaturation|hypersaturated]] with [[cholesterol]] and [[cholesterol]] stones form.  
* Gallstone disease can also be caused by a lack of [[motility]] in the muscular wall of the [[gallbladder]] or excessive [[Sphincter of Oddi|sphincter]] contraction, that prevents [[bile]] secretion.
* Gallstone disease can also be caused by a lack of [[motility]] in the muscular wall of the [[gallbladder]] or excessive [[Sphincter of Oddi|sphincter]] contraction, that prevents [[bile]] secretion.
* In this way the [[bile]] stagnates within the gallbladder and promotes the formation of stones. <ref name="pmid22570746">{{cite journal |vauthors=Stinton LM, Shaffer EA |title=Epidemiology of gallbladder disease: cholelithiasis and cancer |journal=Gut Liver |volume=6 |issue=2 |pages=172–87 |year=2012 |pmid=22570746 |pmc=3343155 |doi=10.5009/gnl.2012.6.2.172 |url=}}</ref><ref name="pmid12242178">{{cite journal |vauthors=Indar AA, Beckingham IJ |title=Acute cholecystitis |journal=BMJ |volume=325 |issue=7365 |pages=639–43 |year=2002 |pmid=12242178 |pmc=1124163 |doi= |url=}}</ref><ref>{{cite book | last = McPhee | first = Stephen | title = Pathophysiology of disease : an introduction to clinical medicine | publisher = McGraw-Hill Education Medical | location = New York | year = 2014 | isbn = 0071806008 }}</ref><ref name="pmid17981556">{{cite journal |vauthors=Wang HH, Portincasa P, Wang DQ |title=Molecular pathophysiology and physical chemistry of cholesterol gallstones |journal=Front. Biosci. |volume=13 |issue= |pages=401–23 |year=2008 |pmid=17981556 |doi= |url=}}</ref><ref>{{cite journal |year=1995 |month=June |title=. |journal=European Journal Gastroenterology & Hepatology |volume=6 |pages=585-593 |accessdate= 2007-08-25}}</ref>
* In this way the [[bile]] stagnates within the gallbladder and promotes the formation of stones.  


===Pathogenesis of Specific Stones===
===Pathogenesis of Specific Stones===


====                                                                                                            Cholesterol Stones Formation====
====                                                                                                            Cholesterol Stones Formation<ref name="pmid22570746">{{cite journal |vauthors=Stinton LM, Shaffer EA |title=Epidemiology of gallbladder disease: cholelithiasis and cancer |journal=Gut Liver |volume=6 |issue=2 |pages=172–87 |year=2012 |pmid=22570746 |pmc=3343155 |doi=10.5009/gnl.2012.6.2.172 |url=}}</ref><ref name="pmid17547709">{{cite journal |vauthors=Marschall HU, Einarsson C |title=Gallstone disease |journal=J. Intern. Med. |volume=261 |issue=6 |pages=529–42 |year=2007 |pmid=17547709 |doi=10.1111/j.1365-2796.2007.01783.x |url=}}</ref><ref name="pmid18579815">{{cite journal |vauthors=Strasberg SM |title=Clinical practice. Acute calculous cholecystitis |journal=N. Engl. J. Med. |volume=358 |issue=26 |pages=2804–11 |year=2008 |pmid=18579815 |doi=10.1056/NEJMcp0800929 |url=}}</ref>====


{{Family tree/start}}
{{Family tree/start}}
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{{Family tree | | | | F01 | | | |F01=Biliary sludge is a [[Viscosity|viscous]] mixture that consists of [[mucin]] [[Glycoprotein|glycoproteins]], [[Calcium|calcium deposits]] and [[cholesterol]] crystals in the gallbladder}}
{{Family tree | | | | F01 | | | |F01=Biliary sludge is a [[Viscosity|viscous]] mixture that consists of [[mucin]] [[Glycoprotein|glycoproteins]], [[Calcium|calcium deposits]] and [[cholesterol]] crystals in the gallbladder}}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | G01 | | | |G01=Over time, this sludge becomes more and more concentrated with [[cholesterol]] and eventually stones form.<ref name="pmid22570746">{{cite journal |vauthors=Stinton LM, Shaffer EA |title=Epidemiology of gallbladder disease: cholelithiasis and cancer |journal=Gut Liver |volume=6 |issue=2 |pages=172–87 |year=2012 |pmid=22570746 |pmc=3343155 |doi=10.5009/gnl.2012.6.2.172 |url=}}</ref><ref name="pmid17547709">{{cite journal |vauthors=Marschall HU, Einarsson C |title=Gallstone disease |journal=J. Intern. Med. |volume=261 |issue=6 |pages=529–42 |year=2007 |pmid=17547709 |doi=10.1111/j.1365-2796.2007.01783.x |url=}}</ref><ref name="pmid18579815">{{cite journal |vauthors=Strasberg SM |title=Clinical practice. Acute calculous cholecystitis |journal=N. Engl. J. Med. |volume=358 |issue=26 |pages=2804–11 |year=2008 |pmid=18579815 |doi=10.1056/NEJMcp0800929 |url=}}</ref>}}
{{Family tree | | | | G01 | | | |G01=Over time, this sludge becomes more and more concentrated with [[cholesterol]] and eventually stones form.}}
{{Family tree/end}}
{{Family tree/end}}


==== Pigment Stones ====
==== Pigment Stones ====
*Less commonly, gallstones can be composed of [[bilirubin]] and are sometimes referred to as "pigment stones".  
*Less commonly, gallstones can be composed of [[bilirubin]] and are sometimes referred to as "pigment stones".<ref name="pmid2022417">{{cite journal |vauthors=Trotman BW |title=Pigment gallstone disease |journal=Gastroenterol. Clin. North Am. |volume=20 |issue=1 |pages=111–26 |year=1991 |pmid=2022417 |doi= |url=}}</ref>
*[[Bilirubin]] is a byproduct of [[red blood cell]] [[Hemolysis|breakdown]] and so are usually found in patients with [[Hemoglobinopathy|hemoglobin disorders]].
*[[Bilirubin]] is a byproduct of [[red blood cell]] [[Hemolysis|breakdown]] and so are usually found in patients with [[Hemoglobinopathy|hemoglobin disorders]].
*Pigment stones are formed via two main pathways:
*Pigment stones are formed via two main pathways:
**[[Infection]] of the biliary tree with bacteria that can release [[Hydrolysis|hydrolytic]] enzymes and form insoluble calcium salts.
**[[Infection]] of the biliary tree with bacteria that can release [[Hydrolysis|hydrolytic]] enzymes and form insoluble calcium salts.
**Nonbacterial, nonenzymatic hydrolysis of [[bilirubin]] conjugates such as what may happen in patients with [[Gilbert's syndrome]] and [[Hemolysis|chronic hemolysis]].<ref name="pmid2022417">{{cite journal |vauthors=Trotman BW |title=Pigment gallstone disease |journal=Gastroenterol. Clin. North Am. |volume=20 |issue=1 |pages=111–26 |year=1991 |pmid=2022417 |doi= |url=}}</ref>
**Nonbacterial, nonenzymatic hydrolysis of [[bilirubin]] conjugates such as what may happen in patients with [[Gilbert's syndrome]] and [[Hemolysis|chronic hemolysis]].
 
====Mixed Stones====
====Mixed Stones====
* There is a lack of evidence that supports a true pathology to explain how mixed stones are formed.
* There is a lack of evidence that supports a true pathology to explain how mixed stones are formed.<ref name="pmid12242178">{{cite journal |vauthors=Indar AA, Beckingham IJ |title=Acute cholecystitis |journal=BMJ |volume=325 |issue=7365 |pages=639–43 |year=2002 |pmid=12242178 |pmc=1124163 |doi= |url=}}</ref>  
* However, there have been theories that include a combination of several mechanisms including supersaturation, infection and hypomotility of the gallbladder.<ref name="pmid12242178">{{cite journal |vauthors=Indar AA, Beckingham IJ |title=Acute cholecystitis |journal=BMJ |volume=325 |issue=7365 |pages=639–43 |year=2002 |pmid=12242178 |pmc=1124163 |doi= |url=}}</ref>
* However, there have been theories that include a combination of several mechanisms including supersaturation, infection and hypomotility of the gallbladder.


==Associated Conditions==
==Associated Conditions==

Revision as of 16:52, 13 December 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Overview

Studies have shown that gallstone formation is mostly due to bile supersaturation. In the United States, patients that present with gallbladder stones mostly have cholesterol stones. Cholesterol stones form when the concentration of cholesterol in the bile is much higher than the concentration of cholesterol that can be dissolved in the bile. Normally cholesterol is metabolized in the body and excess cholesterol is disposed of in the bile. There is a balance between pronucleating (crystallization-promoting) and antinucleating (crystallization-inhibiting) forces, so that gallstones don't form. When pronucleating forces take the upper hand, gallstones will form. On the other hand, moderate intake of wine and the consumption of whole grain bread may decrease the risk of developing gallstones.

Pathophysiology

Pathogenesis of Specific Stones

Cholesterol Stones Formation[1][6][7]

 
 
 
Cholesterol stones are the most common type of gallstone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cholesterol is an important organic molecule that is needed for incorporation within cell membranes and to produce steroid hormones in the body
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The quantity of cholesterol is balanced within the body
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
When there is excess cholesterol in the body, the body will dispose of it by secreting it into the bile
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
When the cholesterol concentration reaches a certain level beyond that that can be secreted into the bile, biliary sludge will start to form
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Biliary sludge is a viscous mixture that consists of mucin glycoproteins, calcium deposits and cholesterol crystals in the gallbladder
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Over time, this sludge becomes more and more concentrated with cholesterol and eventually stones form.
 
 
 

Pigment Stones

Mixed Stones

  • There is a lack of evidence that supports a true pathology to explain how mixed stones are formed.[2]
  • However, there have been theories that include a combination of several mechanisms including supersaturation, infection and hypomotility of the gallbladder.

Associated Conditions


Gross Pathology

  • On gross pathology, commonly multiple small stones are found and less commonly a solitary stone is seen.
  • The smaller stones represent a higher morbidity since they can easily occlude the biliary tracts.[11]
By Noortje123 from nl, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1805918

Microscopic Pathology

  • On microscopic analysis, characteristic findings include:
    • Transmural thickening of the gall bladder wall
    • Neutrophilia[12]

References

  1. 1.0 1.1 Stinton LM, Shaffer EA (2012). "Epidemiology of gallbladder disease: cholelithiasis and cancer". Gut Liver. 6 (2): 172–87. doi:10.5009/gnl.2012.6.2.172. PMC 3343155. PMID 22570746.
  2. 2.0 2.1 Indar AA, Beckingham IJ (2002). "Acute cholecystitis". BMJ. 325 (7365): 639–43. PMC 1124163. PMID 12242178.
  3. McPhee, Stephen (2014). Pathophysiology of disease : an introduction to clinical medicine. New York: McGraw-Hill Education Medical. ISBN 0071806008.
  4. Wang HH, Portincasa P, Wang DQ (2008). "Molecular pathophysiology and physical chemistry of cholesterol gallstones". Front. Biosci. 13: 401–23. PMID 17981556.
  5. European Journal Gastroenterology & Hepatology. 6: 585–593. 1995. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  6. Marschall HU, Einarsson C (2007). "Gallstone disease". J. Intern. Med. 261 (6): 529–42. doi:10.1111/j.1365-2796.2007.01783.x. PMID 17547709.
  7. Strasberg SM (2008). "Clinical practice. Acute calculous cholecystitis". N. Engl. J. Med. 358 (26): 2804–11. doi:10.1056/NEJMcp0800929. PMID 18579815.
  8. Trotman BW (1991). "Pigment gallstone disease". Gastroenterol. Clin. North Am. 20 (1): 111–26. PMID 2022417.
  9. Lv J, Yu C, Guo Y, Bian Z, Yang L, Chen Y, Li S, Huang Y, Fu Y, He P, Tang A, Chen J, Chen Z, Qi L, Li L (2017). "Gallstone Disease and the Risk of Type 2 Diabetes". Sci Rep. 7 (1): 15853. doi:10.1038/s41598-017-14801-2. PMID 29158491.
  10. R.M. Ortega (1997). "Differences in diet and food habits between patients with gallstones and controls". Journal of the American College of Nutrition. 16: 88–95. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help); |access-date= requires |url= (help)
  11. Ansert, Sandra (2018). Textbook of diagnostic sonography. St. Louis, MO: Elsevier. ISBN 978-0323353755.
  12. Fisher, M. M. (1979). Gallstones. Boston, MA: Springer US. ISBN 1461570662.

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