Portal hypertension pathophysiology: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
* Portal hypertension is caused by conditions classified as pre-hepatic, hepatic, and post-hepatic disorders. | * Portal hypertension is caused by conditions classified as pre-[[hepatic]], intra-[[hepatic]], and post-[[hepatic]] disorders. | ||
* The exact pathogenesis in portal hypertension is disturbance in normal physiology of portocaval circulation. | * Intra-[[hepatic]] portal hypertension causes are classified as pre-[[sinusoidal]], [[sinusoidal]], and post-[[sinusoidal]] disorders. | ||
* The exact [[pathogenesis]] in portal hypertension is disturbance in normal physiology of [[Portocaval anastomoses|portocaval circulation]]. | |||
=== Physiology === | === Physiology === | ||
| Line 37: | Line 38: | ||
===Pathogenesis=== | ===Pathogenesis=== | ||
*The | |||
==== Increased resistance ==== | |||
* | * Portal hypertension is related to elevation of [[Portal venous system|portal vasculature]] resistance. | ||
*[ | * Increased resistance in [[Portal venous system|portal system]] can be due to both intra-[[hepatic]] and also portosystemic [[collaterals]] resistances. | ||
* | ** '''Intra-hepatic resistance''' | ||
*[ | *** The main factor in intra-[[hepatic]] resistance is [[hepatic]] vascular [[compliance]], which is greatly decreased in various liver diseases, such as [[fibrosis]] or [[cirrhosis]]. | ||
* | *** Portal hypertension occurs when [[compliance]] is decreased and [[blood flow]] is increased in [[liver]].<ref name="pmid5543903">{{cite journal |vauthors=Greenway CV, Stark RD |title=Hepatic vascular bed |journal=Physiol. Rev. |volume=51 |issue=1 |pages=23–65 |year=1971 |pmid=5543903 |doi= |url=}}</ref> | ||
* | *** Pre-[[hepatic]] and post-[[hepatic]] portal hypertension are due to some secondary obstruction before or after [[liver]] [[vasculature]], respectively.<ref>{{cite book | last = Schiff | first = Eugene | title = Schiff's diseases of the liver | publisher = John Wiley & Sons | location = Chichester, West Sussex, UK | year = 2012 | isbn = 9780470654682 }}</ref> | ||
*** [[Schistosomiasis]] causes both pre-[[sinusoidal]] and [[sinusoidal]] pathologies. The [[granulomas]] compress the pre-[[sinusoidal]] [[veins]]. In late stages [[sinusoidal]] resistance also increased.<ref name="BekerValencia-Parparcén1968">{{cite journal|last1=Beker|first1=Simón G.|last2=Valencia-Parparcén|first2=Joel|title=Portal hypertension syndrome|journal=The American Journal of Digestive Diseases|volume=13|issue=12|year=1968|pages=1047–1054|issn=0002-9211|doi=10.1007/BF02233549}}</ref> | |||
*** [[Alcoholic hepatitis]] causes both [[sinusoidal]] and post-[[sinusoidal]] pathologies.<ref name="pmid13976646">{{cite journal |vauthors=SCHAFFNER F, POPER H |title=Capillarization of hepatic sinusoids in man |journal=Gastroenterology |volume=44 |issue= |pages=239–42 |year=1963 |pmid=13976646 |doi= |url=}}</ref> | |||
*** [[Hepatic]] vascular [[endothelium]] synthesizes and secretes both [[vasodilator]] (e.g., [[nitric oxide]], [[Prostacyclin|prostacyclins]]) and [[vasoconstrictor]] (e.g., [[endothelin]] and [[Prostanoid|prostanoids]]) [[chemicals]].<ref name="pmid1874796">{{cite journal |vauthors=Rubanyi GM |title=Endothelium-derived relaxing and contracting factors |journal=J. Cell. Biochem. |volume=46 |issue=1 |pages=27–36 |year=1991 |pmid=1874796 |doi=10.1002/jcb.240460106 |url=}}</ref> | |||
*** Increased resistance due to the elevation of vascular tone can be caused by [[vasoconstrictors]] excess or [[vasodilators]] lack. | |||
*** It is postulated that in [[Cirrhosis|cirrhotic liver]] the [[nitric oxide]] level is lower and the response to [[endothelin]] response in [[myofibrils]] is higher than normal [[liver]].<ref name="pmid8707268">{{cite journal |vauthors=Rockey DC, Weisiger RA |title=Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance |journal=Hepatology |volume=24 |issue=1 |pages=233–40 |year=1996 |pmid=8707268 |doi=10.1002/hep.510240137 |url=}}</ref> | |||
** '''Portosystemic collateral resistance''' | |||
*** [[Collateral]] formation is the consequence of portal hypertension that is also the main contributor to [[esophageal varices]]. | |||
*** The main purpose of the [[collaterals]] is to decompress and bypass the [[portal]] blood flow. | |||
*** However, the resistance in [[collaterals]] is less than the normal liver. | |||
*** Thus, [[Portocaval anastomoses|portosystemic collaterals]] can not lead to a complete decompression. | |||
*** [[Portocaval anastomoses|Portosystemic collateraling]] occurs between the [[short gastric]], [[coronary]] veins, and the [[esophageal]] [[azygos]] and the [[intercostal veins]]; superior and the middle and inferior [[Hemorrhoidal plexus|hemorrhoidal veins]]; the [[Paraumbilical veins|paraumbilical venous plexus]] and the venous system of abdominal organs juxtaposed with the retroperitoneum and abdominal wall; the left renal vein and the splanchnic, adrenal and spermatic veins.<ref name="pmid1415713">{{cite journal |vauthors=Mosca P, Lee FY, Kaumann AJ, Groszmann RJ |title=Pharmacology of portal-systemic collaterals in portal hypertensive rats: role of endothelium |journal=Am. J. Physiol. |volume=263 |issue=4 Pt 1 |pages=G544–50 |year=1992 |pmid=1415713 |doi= |url=}}</ref> | |||
==== Hyperdynamic circulation in portal hypertension ==== | |||
* Peripheral [[vasodilatation]] is the basis for decreased systemic [[vascular resistance]] and [[mean arterial pressure]], plasma volume expansion, elevated [[splanchnic]] [[blood flow]], and elevated [[cardiac index]]. '''(Colombato et al, 1991).''' | |||
* '''Systemic vasodilation''' | |||
** Three main mechanisms which contribute to the peripheral vasodilation are as following: | |||
*** Increased [[vasodilators]] production in systemic circulation<ref name="pmid2372062">{{cite journal |vauthors=Genecin P, Polio J, Colombato LA, Ferraioli G, Reuben A, Groszmann RJ |title=Bile acids do not mediate the hyperdynamic circulation in portal hypertensive rats |journal=Am. J. Physiol. |volume=259 |issue=1 Pt 1 |pages=G21–5 |year=1990 |pmid=2372062 |doi= |url=}}</ref> | |||
*** Increased [[vasodilators]] production in local [[endothelium]]<ref name="CasadevallPanés1993">{{cite journal|last1=Casadevall|first1=María|last2=Panés|first2=Julián|last3=Piqué|first3=Josep M.|last4=Marroni|first4=Norma|last5=Bosch|first5=Jaume|last6=Whittle|first6=Brendan J. R.|title=Involvement of nitric oxide and prostaglandins in gastric mucosal hyperemia of portal-hypertensive anesthetized rats|journal=Hepatology|volume=18|issue=3|year=1993|pages=628–634|issn=02709139|doi=10.1002/hep.1840180323}}</ref> | |||
*** Decreased vascular response to local [[vasoconstrictors]]<ref name="pmid1616049">{{cite journal |vauthors=Sieber CC, Groszmann RJ |title=In vitro hyporeactivity to methoxamine in portal hypertensive rats: reversal by nitric oxide blockade |journal=Am. J. Physiol. |volume=262 |issue=6 Pt 1 |pages=G996–1001 |year=1992 |pmid=1616049 |doi= |url=}}</ref> | |||
* '''Plasma volume''' | |||
** There are several events which contribute to the [[hyperdynamic circulation]] such as: | |||
*** Initial [[vasodilatation]], induced by systemic and local [[endothelial]] factors | |||
*** Subsequent [[Blood plasma|plasma]] volume expansion<ref name="pmid8425700">{{cite journal |vauthors=Albillos A, Colombato LA, Lee FY, Groszmann RJ |title=Octreotide ameliorates vasodilatation and Na+ retention in portal hypertensive rats |journal=Gastroenterology |volume=104 |issue=2 |pages=575–9 |year=1993 |pmid=8425700 |doi= |url=}}</ref> | |||
==Genetics== | ==Genetics== | ||
*[Disease name] is transmitted in [mode of genetic transmission] pattern. | *[Disease name] is transmitted in [mode of genetic transmission] pattern. | ||
Revision as of 15:48, 24 October 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Portal venous pressure is determined by portal blood flow and portal vascular resistance. Increased portal vascular resistance is often the main factor responsible for it. The consequences of portal hypertension are due to blood being forced down alternate channels by the increased resistance to flow through the portal system. Due to formation of alternate channels initially some of the portal blood and later most of it is shunted directly to the systemic circulation bypassing the liver.
Pathophysiology
- Portal hypertension is caused by conditions classified as pre-hepatic, intra-hepatic, and post-hepatic disorders.
- Intra-hepatic portal hypertension causes are classified as pre-sinusoidal, sinusoidal, and post-sinusoidal disorders.
- The exact pathogenesis in portal hypertension is disturbance in normal physiology of portocaval circulation.
Physiology
- Ohm's law in vascular system defines the pressure gradient in blood vessels as equal to product of blood flow (Q) and vascular resistance (R):<math display="block">\Delta P =P2-P1= Q\times R</math>
- Vascular resistance (R) has to be measured through Pouseuille’s law formula:<math display="block">R = {8 \eta L\over \pi r^4}</math>η= Viscosity; L= Length of vessel; r= Radius of vessel
- When the (R) measurement formula is integrated in Ohm's law it becomes as the following:
<math display="block">\Delta P= P_2-P_1 = {Q\times 8 \eta L\over \pi r^4}</math>
- Length of blood vessels (L) never differs in normal physiologic condition.
- Blood viscosity (η) does not change, unless dramatic changes in hematocrit happen.
- Thus, the main factors that affect the pressure gradient in blood vessels are blood flow (Q) and vessel radius (r) in a direct and inverse way, respectively.
| • Anatomical (irreversible component) • Functional/vascular tone (reversible component) | • Opening of pre-existing vascular channels • Formation of new vascular channels | • Systemic vasodilation (r) • Increasing plasma volume (Q) | |||||||||||||||||||||||||||||||||||||
| lntra-hepatic resistance (r) | Portosystemic collaterals (Q) | ||||||||||||||||||||||||||||||||||||||
| Increased resistance to portal blood flow (R) | Increased systemic/splanchnic blood flow (Q) (hyperdynamic circulation) | ||||||||||||||||||||||||||||||||||||||
| Elevated portal pressure (P) | |||||||||||||||||||||||||||||||||||||||
| Portal hypertension | |||||||||||||||||||||||||||||||||||||||
Pathogenesis
Increased resistance
- Portal hypertension is related to elevation of portal vasculature resistance.
- Increased resistance in portal system can be due to both intra-hepatic and also portosystemic collaterals resistances.
- Intra-hepatic resistance
- The main factor in intra-hepatic resistance is hepatic vascular compliance, which is greatly decreased in various liver diseases, such as fibrosis or cirrhosis.
- Portal hypertension occurs when compliance is decreased and blood flow is increased in liver.[1]
- Pre-hepatic and post-hepatic portal hypertension are due to some secondary obstruction before or after liver vasculature, respectively.[2]
- Schistosomiasis causes both pre-sinusoidal and sinusoidal pathologies. The granulomas compress the pre-sinusoidal veins. In late stages sinusoidal resistance also increased.[3]
- Alcoholic hepatitis causes both sinusoidal and post-sinusoidal pathologies.[4]
- Hepatic vascular endothelium synthesizes and secretes both vasodilator (e.g., nitric oxide, prostacyclins) and vasoconstrictor (e.g., endothelin and prostanoids) chemicals.[5]
- Increased resistance due to the elevation of vascular tone can be caused by vasoconstrictors excess or vasodilators lack.
- It is postulated that in cirrhotic liver the nitric oxide level is lower and the response to endothelin response in myofibrils is higher than normal liver.[6]
- Portosystemic collateral resistance
- Collateral formation is the consequence of portal hypertension that is also the main contributor to esophageal varices.
- The main purpose of the collaterals is to decompress and bypass the portal blood flow.
- However, the resistance in collaterals is less than the normal liver.
- Thus, portosystemic collaterals can not lead to a complete decompression.
- Portosystemic collateraling occurs between the short gastric, coronary veins, and the esophageal azygos and the intercostal veins; superior and the middle and inferior hemorrhoidal veins; the paraumbilical venous plexus and the venous system of abdominal organs juxtaposed with the retroperitoneum and abdominal wall; the left renal vein and the splanchnic, adrenal and spermatic veins.[7]
- Intra-hepatic resistance
Hyperdynamic circulation in portal hypertension
- Peripheral vasodilatation is the basis for decreased systemic vascular resistance and mean arterial pressure, plasma volume expansion, elevated splanchnic blood flow, and elevated cardiac index. (Colombato et al, 1991).
- Systemic vasodilation
- Three main mechanisms which contribute to the peripheral vasodilation are as following:
- Increased vasodilators production in systemic circulation[8]
- Increased vasodilators production in local endothelium[9]
- Decreased vascular response to local vasoconstrictors[10]
- Three main mechanisms which contribute to the peripheral vasodilation are as following:
- Plasma volume
- There are several events which contribute to the hyperdynamic circulation such as:
- Initial vasodilatation, induced by systemic and local endothelial factors
- Subsequent plasma volume expansion[11]
- There are several events which contribute to the hyperdynamic circulation such as:
Genetics
- [Disease name] is transmitted in [mode of genetic transmission] pattern.
- Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
- The development of [disease name] is the result of multiple genetic mutations.
Associated Conditions
Gross Pathology
- On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
- On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
References
- ↑ Greenway CV, Stark RD (1971). "Hepatic vascular bed". Physiol. Rev. 51 (1): 23–65. PMID 5543903.
- ↑ Schiff, Eugene (2012). Schiff's diseases of the liver. Chichester, West Sussex, UK: John Wiley & Sons. ISBN 9780470654682.
- ↑ Beker, Simón G.; Valencia-Parparcén, Joel (1968). "Portal hypertension syndrome". The American Journal of Digestive Diseases. 13 (12): 1047–1054. doi:10.1007/BF02233549. ISSN 0002-9211.
- ↑ SCHAFFNER F, POPER H (1963). "Capillarization of hepatic sinusoids in man". Gastroenterology. 44: 239–42. PMID 13976646.
- ↑ Rubanyi GM (1991). "Endothelium-derived relaxing and contracting factors". J. Cell. Biochem. 46 (1): 27–36. doi:10.1002/jcb.240460106. PMID 1874796.
- ↑ Rockey DC, Weisiger RA (1996). "Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance". Hepatology. 24 (1): 233–40. doi:10.1002/hep.510240137. PMID 8707268.
- ↑ Mosca P, Lee FY, Kaumann AJ, Groszmann RJ (1992). "Pharmacology of portal-systemic collaterals in portal hypertensive rats: role of endothelium". Am. J. Physiol. 263 (4 Pt 1): G544–50. PMID 1415713.
- ↑ Genecin P, Polio J, Colombato LA, Ferraioli G, Reuben A, Groszmann RJ (1990). "Bile acids do not mediate the hyperdynamic circulation in portal hypertensive rats". Am. J. Physiol. 259 (1 Pt 1): G21–5. PMID 2372062.
- ↑ Casadevall, María; Panés, Julián; Piqué, Josep M.; Marroni, Norma; Bosch, Jaume; Whittle, Brendan J. R. (1993). "Involvement of nitric oxide and prostaglandins in gastric mucosal hyperemia of portal-hypertensive anesthetized rats". Hepatology. 18 (3): 628–634. doi:10.1002/hep.1840180323. ISSN 0270-9139.
- ↑ Sieber CC, Groszmann RJ (1992). "In vitro hyporeactivity to methoxamine in portal hypertensive rats: reversal by nitric oxide blockade". Am. J. Physiol. 262 (6 Pt 1): G996–1001. PMID 1616049.
- ↑ Albillos A, Colombato LA, Lee FY, Groszmann RJ (1993). "Octreotide ameliorates vasodilatation and Na+ retention in portal hypertensive rats". Gastroenterology. 104 (2): 575–9. PMID 8425700.