Gastrointestinal varices pathophysiology: Difference between revisions
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'''Vascular architecture and venous drainage of esophagus''' | '''Vascular architecture and venous drainage of esophagus''' | ||
* Vascular resistance increases against portal blood flow in cirrhosis, noncirrhotic portal fibrosis, idiopathic portal hypertension, extrahepatic portal vein obstruction, Budd-Chiari syndrome, and other portal hypertensive disorders, inducing congestion of blood in the splenic and mesenteric veins that lie upstream of the portal trunk<ref name="pmid6023778">{{cite journal |vauthors=Moreno AH, Burchell AR, Rousselot LM, Panke WF, Slafsky F, Burke JH |title=Portal blood flow in cirrhosis of the liver |journal=J. Clin. Invest. |volume=46 |issue=3 |pages=436–45 |year=1967 |pmid=6023778 |pmc=297064 |doi=10.1172/JCI105545 |url=}}</ref><ref name="pmid20066733">{{cite journal |vauthors=Ponziani FR, Zocco MA, Campanale C, Rinninella E, Tortora A, Di Maurizio L, Bombardieri G, De Cristofaro R, De Gaetano AM, Landolfi R, Gasbarrini A |title=Portal vein thrombosis: insight into physiopathology, diagnosis, and treatment |journal=World J. Gastroenterol. |volume=16 |issue=2 |pages=143–55 |year=2010 |pmid=20066733 |pmc=2806552 |doi= |url=}}</ref><ref name="pmid9462648">{{cite journal |vauthors=Tanaka M, Wanless IR |title=Pathology of the liver in Budd-Chiari syndrome: portal vein thrombosis and the histogenesis of veno-centric cirrhosis, veno-portal cirrhosis, and large regenerative nodules |journal=Hepatology |volume=27 |issue=2 |pages=488–96 |year=1998 |pmid=9462648 |doi=10.1002/hep.510270224 |url=}}</ref> | * Vascular resistance increases against portal blood flow in cirrhosis, noncirrhotic portal fibrosis, idiopathic portal hypertension, extrahepatic portal vein obstruction, Budd-Chiari syndrome, and other portal hypertensive disorders, inducing congestion of blood in the splenic and mesenteric veins that lie upstream of the portal trunk<ref name="pmid6023778">{{cite journal |vauthors=Moreno AH, Burchell AR, Rousselot LM, Panke WF, Slafsky F, Burke JH |title=Portal blood flow in cirrhosis of the liver |journal=J. Clin. Invest. |volume=46 |issue=3 |pages=436–45 |year=1967 |pmid=6023778 |pmc=297064 |doi=10.1172/JCI105545 |url=}}</ref><ref name="pmid20066733">{{cite journal |vauthors=Ponziani FR, Zocco MA, Campanale C, Rinninella E, Tortora A, Di Maurizio L, Bombardieri G, De Cristofaro R, De Gaetano AM, Landolfi R, Gasbarrini A |title=Portal vein thrombosis: insight into physiopathology, diagnosis, and treatment |journal=World J. Gastroenterol. |volume=16 |issue=2 |pages=143–55 |year=2010 |pmid=20066733 |pmc=2806552 |doi= |url=}}</ref><ref name="pmid9462648">{{cite journal |vauthors=Tanaka M, Wanless IR |title=Pathology of the liver in Budd-Chiari syndrome: portal vein thrombosis and the histogenesis of veno-centric cirrhosis, veno-portal cirrhosis, and large regenerative nodules |journal=Hepatology |volume=27 |issue=2 |pages=488–96 |year=1998 |pmid=9462648 |doi=10.1002/hep.510270224 |url=}}</ref> | ||
* The major vessels draining blood from the esophagus include, the left gastric (coronary) and less frequently short gastric veins | * The major vessels draining blood from the esophagus include, the left gastric (coronary) and less frequently short gastric veins<ref name="pmid21423905">{{cite journal |vauthors=Adithan S, Venkatesan B, Sundarajan E, Kate V, Kalayarasan R |title=Color Doppler evaluation of left gastric vein hemodynamics in cirrhosis with portal hypertension and its correlation with esophageal varices and variceal bleed |journal=Indian J Radiol Imaging |volume=20 |issue=4 |pages=289–93 |year=2010 |pmid=21423905 |pmc=3056627 |doi=10.4103/0971-3026.73541 |url=}}</ref><ref name="pmid22568419">{{cite journal |vauthors=Rebibo L, Chivot C, Fuks D, Sabbagh C, Yzet T, Regimbeau JM |title=Three-dimensional computed tomography analysis of the left gastric vein in a pancreatectomy |journal=HPB (Oxford) |volume=14 |issue=6 |pages=414–21 |year=2012 |pmid=22568419 |pmc=3384867 |doi=10.1111/j.1477-2574.2012.00468.x |url=}}</ref> | ||
'''Porto-caval collaterals in esophagus''' | '''Porto-caval collaterals in esophagus''' | ||
* Portal hypertension develops due to the formation of porto-collateral circulation | * Portal hypertension develops due to the formation of porto-collateral circulation<ref name="pmid3953799">{{cite journal |vauthors=Sikuler E, Groszmann RJ |title=Interaction of flow and resistance in maintenance of portal hypertension in a rat model |journal=Am. J. Physiol. |volume=250 |issue=2 Pt 1 |pages=G205–12 |year=1986 |pmid=3953799 |doi= |url=}}</ref> | ||
* Dilatation and hypertrophy of preexisting vascular channels lead to the formation of these collateral channels | * Dilatation and hypertrophy of preexisting vascular channels lead to the formation of these collateral channels<ref name="pmid25755456">{{cite journal |vauthors=Sharma M, Rameshbabu CS |title=Collateral pathways in portal hypertension |journal=J Clin Exp Hepatol |volume=2 |issue=4 |pages=338–52 |year=2012 |pmid=25755456 |pmc=3940321 |doi=10.1016/j.jceh.2012.08.001 |url=}}</ref> | ||
* Collaterals develop according to the increased portal pressure, and minimum threshold level of hepatic-venous portal geadient may be 10 mmHg for the development of portosystemic collaterals and esophageal varices | * Collaterals develop according to the increased portal pressure, and minimum threshold level of hepatic-venous portal geadient may be 10 mmHg for the development of portosystemic collaterals and esophageal varices<ref name="pmid18695309">{{cite journal |vauthors=Kumar A, Sharma P, Sarin SK |title=Hepatic venous pressure gradient measurement: time to learn! |journal=Indian J Gastroenterol |volume=27 |issue=2 |pages=74–80 |year=2008 |pmid=18695309 |doi= |url=}}</ref> | ||
'''Role of hepatic vasodilators''' | '''Role of hepatic vasodilators''' | ||
'''(a) Nitric Oxide (NO)''' | '''(a) Nitric Oxide (NO)''' | ||
* Nitric oxide (NO) acts as an intra-hepatic vasodilator | * Nitric oxide (NO) acts as an intra-hepatic vasodilator<ref name="pmid24819865">{{cite journal |vauthors=Simmonds MJ, Detterich JA, Connes P |title=Nitric oxide, vasodilation and the red blood cell |journal=Biorheology |volume=51 |issue=2-3 |pages=121–34 |year=2014 |pmid=24819865 |doi=10.3233/BIR-140653 |url=}}</ref><ref name="pmid12602508">{{cite journal |vauthors=González-Abraldes J, García-Pagán JC, Bosch J |title=Nitric oxide and portal hypertension |journal=Metab Brain Dis |volume=17 |issue=4 |pages=311–24 |year=2002 |pmid=12602508 |doi= |url=}}</ref> | ||
* The levels of NO are decreased in patients suffering from chronic liver disease | * The levels of NO are decreased in patients suffering from chronic liver disease<ref name="pmid10643626">{{cite journal |vauthors=Wiest R, Groszmann RJ |title=Nitric oxide and portal hypertension: its role in the regulation of intrahepatic and splanchnic vascular resistance |journal=Semin. Liver Dis. |volume=19 |issue=4 |pages=411–26 |year=1999 |pmid=10643626 |doi=10.1055/s-2007-1007129 |url=}}</ref> | ||
* This leads to an imbalance between the endogenous vasodilators and vasoconstrictors inside the hepatic vascular tree | * This leads to an imbalance between the endogenous vasodilators and vasoconstrictors inside the hepatic vascular tree | ||
* Reduced levels of hepatic NO production may contribute to the increased intrahepatic vascular resistance in cirrhosis, thereby worsening portal hypertension | * Reduced levels of hepatic NO production may contribute to the increased intrahepatic vascular resistance in cirrhosis, thereby worsening portal hypertension<ref name="urlNitric Oxide - Hepatic Circulation - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK53065/ |title=Nitric Oxide - Hepatic Circulation - NCBI Bookshelf |format= |work= |accessdate=}}</ref> | ||
* NO-dependent apoptosis maintains the hepatic sinusoidal homeostasis | * NO-dependent apoptosis maintains the hepatic sinusoidal homeostasis | ||
* NO also leads to apoptosis of hepatic stellate cell through a signaling mechanism that involves mitochondria, and a decreased level of NO may lead to a disturbance of the intra-hepatic homeostasis | * NO also leads to apoptosis of hepatic stellate cell through a signaling mechanism that involves mitochondria, and a decreased level of NO may lead to a disturbance of the intra-hepatic homeostasis<ref name="pmid18459124">{{cite journal |vauthors=Langer DA, Das A, Semela D, Kang-Decker N, Hendrickson H, Bronk SF, Katusic ZS, Gores GJ, Shah VH |title=Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species |journal=Hepatology |volume=47 |issue=6 |pages=1983–93 |year=2008 |pmid=18459124 |pmc=2562502 |doi=10.1002/hep.22285 |url=}}</ref> | ||
'''(b) Glucagon''' | '''(b) Glucagon''' | ||
* Glucagon is a hormonal vasodilator which is associated with increased blood flow in the splanchnic bed and portal hypertension | * Glucagon is a hormonal vasodilator which is associated with increased blood flow in the splanchnic bed and portal hypertension<ref name="pmid21160999">{{cite journal |vauthors=Martell M, Coll M, Ezkurdia N, Raurell I, Genescà J |title=Physiopathology of splanchnic vasodilation in portal hypertension |journal=World J Hepatol |volume=2 |issue=6 |pages=208–20 |year=2010 |pmid=21160999 |pmc=2999290 |doi=10.4254/wjh.v2.i6.208 |url=}}</ref> | ||
* Plasma glucagon levels are increased in cirrhotic patients due to decreased hepatic clearance of glucagon as well as an increased secretion of glucagon by | * Plasma glucagon levels are increased in cirrhotic patients due to decreased hepatic clearance of glucagon as well as an increased secretion of glucagon by pancreatic alpha cells<ref name="pmid21160999">{{cite journal |vauthors=Martell M, Coll M, Ezkurdia N, Raurell I, Genescà J |title=Physiopathology of splanchnic vasodilation in portal hypertension |journal=World J Hepatol |volume=2 |issue=6 |pages=208–20 |year=2010 |pmid=21160999 |pmc=2999290 |doi=10.4254/wjh.v2.i6.208 |url=}}</ref><ref name="pmid8175150">{{cite journal |vauthors=Gomis R, Fernández-Alvarez J, Pizcueta P, Fernández M, Casamitjana R, Bosch J, Rodés J |title=Impaired function of pancreatic islets from rats with portal hypertension resulting from cirrhosis and partial portal vein ligation |journal=Hepatology |volume=19 |issue=5 |pages=1257–61 |year=1994 |pmid=8175150 |doi= |url=}}</ref> | ||
* Hyperglucagonemia may play a part in splanchnic vasodilatation of chronic portal hypertension | * Hyperglucagonemia may play a part in splanchnic vasodilatation of chronic portal hypertension<ref name="pmid26266087">{{cite journal |vauthors=Hansen JS, Clemmesen JO, Secher NH, Hoene M, Drescher A, Weigert C, Pedersen BK, Plomgaard P |title=Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans |journal=Mol Metab |volume=4 |issue=8 |pages=551–60 |year=2015 |pmid=26266087 |pmc=4529499 |doi=10.1016/j.molmet.2015.06.001 |url=}}</ref><ref name="Tibblin1970">{{cite journal|last1=Tibblin|first1=Sten|title=Splanchnic Hemodynamic Responses to Glucagon|journal=Archives of Surgery|volume=100|issue=1|year=1970|pages=84|issn=0004-0010|doi=10.1001/archsurg.1970.01340190086020}}</ref><ref name="pmid10643627">{{cite journal |vauthors=García-Pagán JC, Escorsell A, Moitinho E, Bosch J |title=Influence of pharmacological agents on portal hemodynamics: basis for its use in the treatment of portal hypertension |journal=Semin. Liver Dis. |volume=19 |issue=4 |pages=427–38 |year=1999 |pmid=10643627 |doi= |url=}}</ref> | ||
'''(c) Prostacyclin''' | '''(c) Prostacyclin''' | ||
* Prostacyclin is an endogenous vasodilator | * Prostacyclin is an endogenous vasodilator | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Pathophysiology
Varices arise from hemodynamic disturbance between the systemic and portal venous system. The majority of venous drainage of the gastrointestinal system occurs via the portal venous system. Whenever there is an interruption of drainage through the portal system (for example due to cirrhosis), the vessels contributing to the porto-caval shunts become more prominent due to increased pressure gradient. The interruption in blood flow leads to the creation collateral vessels that involve veins of the esophagus, stomach, pelvis (hemorrhoids), retroperitoneum, liver, abdominal wall, and other areas.[1][2]
Esophageal varices
Esophageal varices are a major complication of portal hypertension (increased blood pressure in the portal venous system). In order to understand the mechanism leading to the development of esophageal varices, it is important to understand the normal vascular architecture and venous drainage of the esophagus.[3]
Vascular architecture and venous drainage of esophagus
- Vascular resistance increases against portal blood flow in cirrhosis, noncirrhotic portal fibrosis, idiopathic portal hypertension, extrahepatic portal vein obstruction, Budd-Chiari syndrome, and other portal hypertensive disorders, inducing congestion of blood in the splenic and mesenteric veins that lie upstream of the portal trunk[4][5][6]
- The major vessels draining blood from the esophagus include, the left gastric (coronary) and less frequently short gastric veins[7][8]
Porto-caval collaterals in esophagus
- Portal hypertension develops due to the formation of porto-collateral circulation[9]
- Dilatation and hypertrophy of preexisting vascular channels lead to the formation of these collateral channels[10]
- Collaterals develop according to the increased portal pressure, and minimum threshold level of hepatic-venous portal geadient may be 10 mmHg for the development of portosystemic collaterals and esophageal varices[11]
Role of hepatic vasodilators
(a) Nitric Oxide (NO)
- Nitric oxide (NO) acts as an intra-hepatic vasodilator[12][13]
- The levels of NO are decreased in patients suffering from chronic liver disease[14]
- This leads to an imbalance between the endogenous vasodilators and vasoconstrictors inside the hepatic vascular tree
- Reduced levels of hepatic NO production may contribute to the increased intrahepatic vascular resistance in cirrhosis, thereby worsening portal hypertension[15]
- NO-dependent apoptosis maintains the hepatic sinusoidal homeostasis
- NO also leads to apoptosis of hepatic stellate cell through a signaling mechanism that involves mitochondria, and a decreased level of NO may lead to a disturbance of the intra-hepatic homeostasis[16]
(b) Glucagon
- Glucagon is a hormonal vasodilator which is associated with increased blood flow in the splanchnic bed and portal hypertension[17]
- Plasma glucagon levels are increased in cirrhotic patients due to decreased hepatic clearance of glucagon as well as an increased secretion of glucagon by pancreatic alpha cells[17][18]
- Hyperglucagonemia may play a part in splanchnic vasodilatation of chronic portal hypertension[19][20][21]
(c) Prostacyclin
- Prostacyclin is an endogenous vasodilator
- Prostacyclin levels are inversely related to the size of varices
- Decreased prostacyclin levels are found in cirrhotic patients
Role of hepatic vasoconstrictors
(a) Endothelin
(b) Angiotensin II
(c) Norepinephrine
Role of endothelial dysfunction
Associated Conditions
Genetics
Gross Pathology
Microscopic Pathology
- ↑ "Anatomy - The Gastrointestinal Circulation - NCBI Bookshelf".
- ↑ Mahl TC, Groszmann RJ (1990). "Pathophysiology of portal hypertension and variceal bleeding". Surg. Clin. North Am. 70 (2): 251–66. PMID 2181704.
- ↑ Maruyama H, Yokosuka O (2012). "Pathophysiology of portal hypertension and esophageal varices". Int J Hepatol. 2012: 895787. doi:10.1155/2012/895787. PMC 3362051. PMID 22666604.
- ↑ Moreno AH, Burchell AR, Rousselot LM, Panke WF, Slafsky F, Burke JH (1967). "Portal blood flow in cirrhosis of the liver". J. Clin. Invest. 46 (3): 436–45. doi:10.1172/JCI105545. PMC 297064. PMID 6023778.
- ↑ Ponziani FR, Zocco MA, Campanale C, Rinninella E, Tortora A, Di Maurizio L, Bombardieri G, De Cristofaro R, De Gaetano AM, Landolfi R, Gasbarrini A (2010). "Portal vein thrombosis: insight into physiopathology, diagnosis, and treatment". World J. Gastroenterol. 16 (2): 143–55. PMC 2806552. PMID 20066733.
- ↑ Tanaka M, Wanless IR (1998). "Pathology of the liver in Budd-Chiari syndrome: portal vein thrombosis and the histogenesis of veno-centric cirrhosis, veno-portal cirrhosis, and large regenerative nodules". Hepatology. 27 (2): 488–96. doi:10.1002/hep.510270224. PMID 9462648.
- ↑ Adithan S, Venkatesan B, Sundarajan E, Kate V, Kalayarasan R (2010). "Color Doppler evaluation of left gastric vein hemodynamics in cirrhosis with portal hypertension and its correlation with esophageal varices and variceal bleed". Indian J Radiol Imaging. 20 (4): 289–93. doi:10.4103/0971-3026.73541. PMC 3056627. PMID 21423905.
- ↑ Rebibo L, Chivot C, Fuks D, Sabbagh C, Yzet T, Regimbeau JM (2012). "Three-dimensional computed tomography analysis of the left gastric vein in a pancreatectomy". HPB (Oxford). 14 (6): 414–21. doi:10.1111/j.1477-2574.2012.00468.x. PMC 3384867. PMID 22568419.
- ↑ Sikuler E, Groszmann RJ (1986). "Interaction of flow and resistance in maintenance of portal hypertension in a rat model". Am. J. Physiol. 250 (2 Pt 1): G205–12. PMID 3953799.
- ↑ Sharma M, Rameshbabu CS (2012). "Collateral pathways in portal hypertension". J Clin Exp Hepatol. 2 (4): 338–52. doi:10.1016/j.jceh.2012.08.001. PMC 3940321. PMID 25755456.
- ↑ Kumar A, Sharma P, Sarin SK (2008). "Hepatic venous pressure gradient measurement: time to learn!". Indian J Gastroenterol. 27 (2): 74–80. PMID 18695309.
- ↑ Simmonds MJ, Detterich JA, Connes P (2014). "Nitric oxide, vasodilation and the red blood cell". Biorheology. 51 (2–3): 121–34. doi:10.3233/BIR-140653. PMID 24819865.
- ↑ González-Abraldes J, García-Pagán JC, Bosch J (2002). "Nitric oxide and portal hypertension". Metab Brain Dis. 17 (4): 311–24. PMID 12602508.
- ↑ Wiest R, Groszmann RJ (1999). "Nitric oxide and portal hypertension: its role in the regulation of intrahepatic and splanchnic vascular resistance". Semin. Liver Dis. 19 (4): 411–26. doi:10.1055/s-2007-1007129. PMID 10643626.
- ↑ "Nitric Oxide - Hepatic Circulation - NCBI Bookshelf".
- ↑ Langer DA, Das A, Semela D, Kang-Decker N, Hendrickson H, Bronk SF, Katusic ZS, Gores GJ, Shah VH (2008). "Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species". Hepatology. 47 (6): 1983–93. doi:10.1002/hep.22285. PMC 2562502. PMID 18459124.
- ↑ 17.0 17.1 Martell M, Coll M, Ezkurdia N, Raurell I, Genescà J (2010). "Physiopathology of splanchnic vasodilation in portal hypertension". World J Hepatol. 2 (6): 208–20. doi:10.4254/wjh.v2.i6.208. PMC 2999290. PMID 21160999.
- ↑ Gomis R, Fernández-Alvarez J, Pizcueta P, Fernández M, Casamitjana R, Bosch J, Rodés J (1994). "Impaired function of pancreatic islets from rats with portal hypertension resulting from cirrhosis and partial portal vein ligation". Hepatology. 19 (5): 1257–61. PMID 8175150.
- ↑ Hansen JS, Clemmesen JO, Secher NH, Hoene M, Drescher A, Weigert C, Pedersen BK, Plomgaard P (2015). "Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans". Mol Metab. 4 (8): 551–60. doi:10.1016/j.molmet.2015.06.001. PMC 4529499. PMID 26266087.
- ↑ Tibblin, Sten (1970). "Splanchnic Hemodynamic Responses to Glucagon". Archives of Surgery. 100 (1): 84. doi:10.1001/archsurg.1970.01340190086020. ISSN 0004-0010.
- ↑ García-Pagán JC, Escorsell A, Moitinho E, Bosch J (1999). "Influence of pharmacological agents on portal hemodynamics: basis for its use in the treatment of portal hypertension". Semin. Liver Dis. 19 (4): 427–38. PMID 10643627.