Portal hypertension pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
Line 71: Line 71:


==Genetics==
==Genetics==
*Genes involved in the pathogenesis of portal hypertension include the following:
*[[Genes]] involved in the [[pathogenesis]] of portal hypertension include the following:
{| class="wikitable"
{| class="wikitable"
!Gene
!Gene
Line 80: Line 80:
!Notes
!Notes
|-
|-
|'''Deoxyguanosine kinase (DGUOK)'''  
|'''[[DGUOK|Deoxyguanosine kinase (DGUOK)]]'''  
|601465  
|601465  
|2p13.1
|2p13.1
|DNA replication
|[[DNA replication]]
|Point mutation
|[[Point mutation]]
|Mutation leads to:  
|[[Mutation]] leads to:  
* Liver failure  
* [[Liver failure]]
* Neurologic abnormalities
* [[Neurologic]] abnormalities
* Hypoglycemia
* [[Hypoglycemia]]
* Increased lactate in body fluids
* Increased [[Lactic acid|lactate]] in [[body fluids]]
|-
|-
|'''Adenosine deaminase (ADA)'''
|'''[[Adenosine deaminase|Adenosine deaminase (ADA)]]'''
|608958  
|608958  
|20q13.12
|20q13.12
|Irreversible deamination of adenosine and deoxyadenosine  
|Irreversible [[deamination]] of [[adenosine]] and [[deoxyadenosine]]
|Reduced  
|Reduced  
|Some roles in modulating tissue response to IL-13
|Some roles in modulating tissue response to [[Interleukin 13|IL-13]]


The main effects of IL-13 are:
The main effects of [[IL-13]] are:
* Inflammation
* [[Inflammation]]
* Chemokine elaboration
* [[Chemokine]] elaboration
* Fibrosis
* [[Fibrosis]]
|-
|-
|'''Phospholipase A2 (PL2G10)'''  
|'''[[Phospholipase A2|Phospholipase A2 (PL2G10)]]'''  
|603603  
|603603  
|16p13.12
|16p13.12
|Catalyzing the release of fatty acids from phospholipids
|Catalyzing the release of [[Fatty acid|fatty acids]] from [[phospholipids]]
|Reduced  
|Reduced  
|Identifier of PL2G10 expression:
|Identifier of PL2G10 expression:
* Arachidonic acid (AA)
* [[Arachidonic acid|Arachidonic acid (AA)]]
* Prostaglandins (PG)
* [[Prostaglandins|Prostaglandins (PG)]]
* Leukotrienes (LT)
* [[Leukotrienes|Leukotrienes (LT)]]
|-
|-
|'''Cytochrome P450, family 4, subfamily F, polypeptide 3 (CYP4F3)'''
|'''[[CYP4F3|Cytochrome P450, family 4, subfamily F, polypeptide 3 (CYP4F3)]]'''
|601270  
|601270  
|19p13.12
|19p13.12
|Catalyzing the omega-hydroxylation of leukotriene B4 (LTB4)
|Catalyzing the omega-[[hydroxylation]] of [[Leukotriene B4|leukotriene B4 (LTB4)]]
|Increased  
|Increased  
| -
| -
|-
|-
|'''Glutathione peroxidase 3 (GPX3)'''
|'''[[Glutathione peroxidase|Glutathione peroxidase 3 (GPX3)]]'''
|138321  
|138321  
|5q33.1
|5q33.1
|Glutathione reduction which reduce:
|[[Glutathione]] reduction which reduce:
* Hydrogen peroxide
* [[Hydrogen peroxide]]
* Organic hydroperoxide
* [[Organic peroxide|Organic hydroperoxide]]
* Lipid peroxides
* [[Lipid peroxidation|Lipid peroxides]]
|Increased  
|Increased  
|Protects various organs against oxidative stress:
|Protects various organs against [[oxidative stress]]:
* Liver
* [[Liver]]
* Kidney
* [[Kidney]]
* Breast
* [[Breast]]
|-
|-
|'''Leukotriene B4 (LTB4)'''
|'''[[Leukotriene B4|Leukotriene B4 (LTB4)]]'''
|601531  
|601531  
|14q12
|14q12
|
|
* Increasing intra-cellular calcium
* Increasing intra-cellular [[calcium]]
* Elevation of inositol 3-phosphate (IP3)  
* Elevation of [[Inositol-3-phosphate synthase|inositol 3-phosphate (IP3)]]
* Inhibition of adenylyl cyclase
* Inhibition of [[Adenylate cyclase|adenylyl cyclase]]
|Mutated
|Mutated
|Increase blood flow to target tissue (esp. heart) about 4 times more.
|Increase [[blood flow]] to target [[tissue]] (esp. [[heart]]) about 4 times more.
|-
|-
|'''Prostaglandin E receptor 2 (PTGER2)'''
|'''[[Prostaglandin E2 receptor|Prostaglandin E receptor 2 (PTGER2)]]'''
|176804  
|176804  
|14q22.1
|14q22.1
Line 150: Line 150:
| -
| -
|-
|-
|'''Endothelin (EDN1)'''
|'''[[Endothelin|Endothelin (EDN1)]]'''
|131240  
|131240  
|6p24.1
|6p24.1
|Vasoconstriction
|[[Vasoconstriction]]
|Increased  
|Increased  
|The most powerful vasoconstrictor known
|The most powerful [[vasoconstrictor]] known
|-
|-
|'''Endothelin receptor type A (EDNRA)'''
|'''[[Endothelin receptor type A|Endothelin receptor type A (EDNRA)]]'''
|131243  
|131243  
|4q31.22-q31.23
|4q31.22-q31.23
|Vasoconstriction through binding to endothelin
|[[Vasoconstriction]] through binding to [[endothelin]]
|Reduced  
|Reduced  
|Directly related to hypertension in patients
|Directly related to [[hypertension]] in patients
|-
|-
|'''Natriuretic peptide receptor 3 (NPR3)'''
|'''[[Natriuretic peptides|Natriuretic peptide receptor 3 (NPR3)]]'''
|108962  
|108962  
|5p13.3
|5p13.3
|Maintenance of:
|Maintenance of:
* Blood pressure  
* [[Blood pressure]]
* Extracellular fluid volume
* [[Extracellular fluid|Extracellular fluid volume]]
|Increased  
|Increased  
|Released from heart muscle in response to increase in wall tension
|Released from [[heart muscle]] in response to increase in wall tension
|-
|-
|'''Cluster of differentiation 44 (CD44)'''
|'''[[Cluster of differentiation|Cluster of differentiation 44 (CD44)]]'''
|107269  
|107269  
|11p13
|11p13
|
|
* Lymphocyte activation  
* [[Lymphocyte]] activation  
* Lymph node homing
* [[Lymph node]] homing
|Reduced  
|Reduced  
|
|
* Related to fibroblast growth factor (FGF)  
* Related to [[Fibroblast growth factor|fibroblast growth factor (FGF)]]
* Increased expression during collateral arteriogenesis  
* Increased expression during [[collateral]] [[arteriogenesis]]
|-
|-
|'''Transforming growth factor (TGF)-β'''
|'''[[Transforming growth factor-β|Transforming growth factor (TGF)-β]]'''
|190180  
|190180  
|19q13.2
|19q13.2
|
|
* Tissue transformation
* [[Transformation|Tissue transformation]]
* Apoptosis regulation
* [[Apoptosis]] regulation
|Reduced  
|Reduced  
|Hyper-expressed in African-American hypertensive patients
|Hyper-expressed in African-American hypertensive patients
Line 196: Line 196:
|607577  
|607577  
|8p21.3
|8p21.3
|Increasing phosphatase activity in intracellular membrane-bound nucleosides
|Increasing [[phosphatase]] activity in [[intracellular]] membrane-bound [[nucleosides]]
|Reduced  
|Reduced  
| -
| -
|-
|-
|'''ATP-binding cassette, subfamily C, member 1 (ABCC1)'''
|'''[[ABCC1|ATP-binding cassette, subfamily C, member 1 (ABCC1)]]'''
|158343
|158343
|16p13.11
|16p13.11
|Multi-drug resistance in small cell lung cancer
|[[Multidrug resistance|Multi-drug resistance]] in [[small cell lung cancer]]
|Reduced  
|Reduced  
| -
| -
Line 209: Line 209:


=== Deoxyguanosine kinase (DGUOK) gene ===
=== Deoxyguanosine kinase (DGUOK) gene ===
* Deoxyguanosine kinase (DGUOK) [[gene]] with [[OMIM]] number of 601465 is on [[chromosome]] 2p13.1.  
* [[DGUOK|Deoxyguanosine kinase (DGUOK)]] [[gene]] with [[OMIM]] number of 601465 is on [[chromosome]] 2p13.1.  
* Point mutation in deoxyguanosine kinase (DGUOK) [[gene]] causes progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids.<ref name="pmid11687800">{{cite journal |vauthors=Mandel H, Szargel R, Labay V, Elpeleg O, Saada A, Shalata A, Anbinder Y, Berkowitz D, Hartman C, Barak M, Eriksson S, Cohen N |title=The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA |journal=Nat. Genet. |volume=29 |issue=3 |pages=337–41 |year=2001 |pmid=11687800 |doi=10.1038/ng746 |url=}}</ref>
* [[Point mutation]] in [[DGUOK|deoxyguanosine kinase (DGUOK)]] [[gene]] causes progressive [[liver failure]] and [[neurologic]] abnormalities, [[hypoglycemia]], and increased [[lactate]] in [[body fluids]].<ref name="pmid11687800">{{cite journal |vauthors=Mandel H, Szargel R, Labay V, Elpeleg O, Saada A, Shalata A, Anbinder Y, Berkowitz D, Hartman C, Barak M, Eriksson S, Cohen N |title=The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA |journal=Nat. Genet. |volume=29 |issue=3 |pages=337–41 |year=2001 |pmid=11687800 |doi=10.1038/ng746 |url=}}</ref>
* Homozygous missense mutation in DGUOK gene found to be related with non-cirrhotic portal hypertension.<ref name="pmid26874653">{{cite journal |vauthors=Vilarinho S, Sari S, Yilmaz G, Stiegler AL, Boggon TJ, Jain D, Akyol G, Dalgic B, Günel M, Lifton RP |title=Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension |journal=Hepatology |volume=63 |issue=6 |pages=1977–86 |year=2016 |pmid=26874653 |pmc=4874872 |doi=10.1002/hep.28499 |url=}}</ref>
* [[Homozygous]] [[missense mutation]] in [[DGUOK]] gene found to be related with [[non-cirrhotic portal hypertension]].<ref name="pmid26874653">{{cite journal |vauthors=Vilarinho S, Sari S, Yilmaz G, Stiegler AL, Boggon TJ, Jain D, Akyol G, Dalgic B, Günel M, Lifton RP |title=Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension |journal=Hepatology |volume=63 |issue=6 |pages=1977–86 |year=2016 |pmid=26874653 |pmc=4874872 |doi=10.1002/hep.28499 |url=}}</ref>


=== Adenosine deaminase (ADA) gene ===
=== Adenosine deaminase (ADA) gene ===
*Adenosine deaminase (ADA) [[gene]] with [[OMIM]] number of 608958 is on [[chromosome]] 20q13.12. ADA [[gene]] is responsible for irreversible deamination of adenosine and deoxyadenosine in the purine catabolic pathway.
*[[Adenosine deaminase|Adenosine deaminase (ADA)]] [[gene]] with [[OMIM]] number of 608958 is on [[chromosome]] 20q13.12. ADA [[gene]] is responsible for irreversible [[deamination]] of [[adenosine]] and [[deoxyadenosine]] in the [[Purine metabolism|purine catabolic pathway]].
*It is postulated that ADA gene expression is reduced in portal hypertension.<ref name="KotaniKawabe2015">{{cite journal|last1=Kotani|first1=Kohei|last2=Kawabe|first2=Joji|last3=Morikawa|first3=Hiroyasu|last4=Akahoshi|first4=Tomohiko|last5=Hashizume|first5=Makoto|last6=Shiomi|first6=Susumu|title=Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension|journal=Mediators of Inflammation|volume=2015|year=2015|pages=1–10|issn=0962-9351|doi=10.1155/2015/349215}}</ref>
*It is postulated that [[Adenosine deaminase|ADA]] gene expression is reduced in portal hypertension.<ref name="KotaniKawabe2015">{{cite journal|last1=Kotani|first1=Kohei|last2=Kawabe|first2=Joji|last3=Morikawa|first3=Hiroyasu|last4=Akahoshi|first4=Tomohiko|last5=Hashizume|first5=Makoto|last6=Shiomi|first6=Susumu|title=Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension|journal=Mediators of Inflammation|volume=2015|year=2015|pages=1–10|issn=0962-9351|doi=10.1155/2015/349215}}</ref>
*Adenosine and adenosine signaling have some roles in modulating the tissue response to IL-13. The main effects of IL-13 are inflammation, chemokine elaboration, and fibrosis.<ref name="pmid12897202">{{cite journal |vauthors=Blackburn MR, Lee CG, Young HW, Zhu Z, Chunn JL, Kang MJ, Banerjee SK, Elias JA |title=Adenosine mediates IL-13-induced inflammation and remodeling in the lung and interacts in an IL-13-adenosine amplification pathway |journal=J. Clin. Invest. |volume=112 |issue=3 |pages=332–44 |year=2003 |pmid=12897202 |pmc=166289 |doi=10.1172/JCI16815 |url=}}</ref>
*[[Adenosine]] and [[adenosine]] signaling have some roles in modulating the tissue response to [[Interleukin 13|IL-13]]. The main effects of [[Interleukin 13|IL-13]] are [[inflammation]], [[chemokine]] elaboration, and [[fibrosis]].<ref name="pmid12897202">{{cite journal |vauthors=Blackburn MR, Lee CG, Young HW, Zhu Z, Chunn JL, Kang MJ, Banerjee SK, Elias JA |title=Adenosine mediates IL-13-induced inflammation and remodeling in the lung and interacts in an IL-13-adenosine amplification pathway |journal=J. Clin. Invest. |volume=112 |issue=3 |pages=332–44 |year=2003 |pmid=12897202 |pmc=166289 |doi=10.1172/JCI16815 |url=}}</ref>


=== Phospholipase A2 (PL2G10) gene ===
=== Phospholipase A2 (PL2G10) gene ===
* Phospholipase A2 (PL2G10) [[gene]] with [[OMIM]] number of 603603 is on [[chromosome]] 16p13.12. PL2G10 [[gene]] is responsible for catalyzing the release of fatty acids from phospholipids.
* [[Phospholipase A2|Phospholipase A2 (PL2G10)]] [[gene]] with [[OMIM]] number of 603603 is on [[chromosome]] 16p13.12. PL2G10 [[gene]] is responsible for catalyzing the release of [[Fatty acid|fatty acids]] from [[phospholipids]].
* It is postulated that PL2G10 gene expression is reduced in portal hypertension.<ref name="KotaniKawabe2015" />
* It is postulated that [[Phospholipase A2|PL2G10]] [[gene]] expression is reduced in portal hypertension.<ref name="KotaniKawabe2015" />
* Arachidonic acid (AA), prostaglandins (PG), and leukotrienes (LT) measurements in patients of portal hypertension show the level of PL2G10 expression.
* [[Arachidonic acid|Arachidonic acid (AA)]], [[Prostaglandins|prostaglandins (PG)]], and [[Leukotrienes|leukotrienes (LT)]] measurements in patients of portal hypertension show the level of [[Phospholipase A2|PL2G10]] expression.


=== Cytochrome P450, family 4, subfamily F, polypeptide 3 (CYP4F3) gene ===
=== Cytochrome P450, family 4, subfamily F, polypeptide 3 (CYP4F3) gene ===
*Cytochrome P450, family 4, subfamily F, polypeptide 3 (CYP4F3) [[gene]] with [[OMIM]] number of 601270 is on [[chromosome]] 19p13.12. CYP4F3 [[gene]] is responsible for catalyzing the omega-hydroxylation of leukotriene B4 (LTB4).
*[[CYP4F3|Cytochrome P450, family 4, subfamily F, polypeptide 3 (CYP4F3)]] [[gene]] with [[OMIM]] number of 601270 is on [[chromosome]] 19p13.12. [[CYP4F3]] [[gene]] is responsible for catalyzing the omega-[[hydroxylation]] of [[Leukotriene B4|leukotriene B4 (LTB4)]].
*It is postulated that CYP4F3 gene expression is increased in portal hypertension.<ref name="KotaniKawabe2015" />
*It is postulated that [[CYP4F3]] [[gene expression]] is increased in portal hypertension.<ref name="KotaniKawabe2015" />


=== Glutathione peroxidase 3 (GPX3) gene ===
=== Glutathione peroxidase 3 (GPX3) gene ===
*Glutathione peroxidase 3 (GPX3) [[gene]] with [[OMIM]] number of 138321 is on [[chromosome]] 5q33.1. GPX3 [[gene]] is responsible for catalyzing glutathione reduction; through which hydrogen peroxide, organic hydroperoxide, and lipid peroxides are reduced.<ref name="pmid3015592">{{cite journal |vauthors=Chambers I, Frampton J, Goldfarb P, Affara N, McBain W, Harrison PR |title=The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the 'termination' codon, TGA |journal=EMBO J. |volume=5 |issue=6 |pages=1221–7 |year=1986 |pmid=3015592 |pmc=1166931 |doi= |url=}}</ref>
*[[Glutathione peroxidase|Glutathione peroxidase 3 (GPX3)]] [[gene]] with [[OMIM]] number of 138321 is on [[chromosome]] 5q33.1. [[Glutathione peroxidase|GPX3]] [[gene]] is responsible for catalyzing [[glutathione]] reduction; through which [[hydrogen peroxide]], [[Organic peroxide|organic hydroperoxide]], and lipid [[peroxides]] are reduced.<ref name="pmid3015592">{{cite journal |vauthors=Chambers I, Frampton J, Goldfarb P, Affara N, McBain W, Harrison PR |title=The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the 'termination' codon, TGA |journal=EMBO J. |volume=5 |issue=6 |pages=1221–7 |year=1986 |pmid=3015592 |pmc=1166931 |doi= |url=}}</ref>
*It is postulated that GPX3 gene expression is increased in portal hypertension.<ref name="KotaniKawabe2015" />
*It is postulated that [[Glutathione peroxidase|GPX3]] [[gene expression]] is increased in portal hypertension.<ref name="KotaniKawabe2015" />
*Glutathione peroxidase 3 protects various organs against oxidative stress, such as liver, kidney, and breast.<ref name="pmid1339300">{{cite journal |vauthors=Chu FF, Esworthy RS, Doroshow JH, Doan K, Liu XF |title=Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents |journal=Blood |volume=79 |issue=12 |pages=3233–8 |year=1992 |pmid=1339300 |doi= |url=}}</ref>
*[[Glutathione peroxidase|Glutathione peroxidase 3]] protects various organs against [[oxidative stress]], such as [[liver]], [[kidney]], and [[breast]].<ref name="pmid1339300">{{cite journal |vauthors=Chu FF, Esworthy RS, Doroshow JH, Doan K, Liu XF |title=Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents |journal=Blood |volume=79 |issue=12 |pages=3233–8 |year=1992 |pmid=1339300 |doi= |url=}}</ref>


=== Leukotriene B4 (LTB4) gene ===
=== Leukotriene B4 (LTB4) gene ===
* Leukotriene B4 (LTB4) [[gene]] with [[OMIM]] number of 601531 is on [[chromosome]] 14q12. LTB4 [[gene]] is responsible for increasing intra-cellular calcium, elevation of inositol 3-phosphate (IP3) concentration, and inhibition of adenylyl cyclase.<ref name="pmid9177352">{{cite journal |vauthors=Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T |title=A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis |journal=Nature |volume=387 |issue=6633 |pages=620–4 |year=1997 |pmid=9177352 |doi=10.1038/42506 |url=}}</ref>
* [[Leukotriene B4|Leukotriene B4 (LTB4)]] [[gene]] with [[OMIM]] number of 601531 is on [[chromosome]] 14q12. [[Leukotriene B4|LTB4]] [[gene]] is responsible for increasing intra-cellular [[calcium]], elevation of [[Inositol triphosphate|inositol 3-phosphate (IP3)]] concentration, and inhibition of [[adenylyl cyclase]].<ref name="pmid9177352">{{cite journal |vauthors=Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T |title=A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis |journal=Nature |volume=387 |issue=6633 |pages=620–4 |year=1997 |pmid=9177352 |doi=10.1038/42506 |url=}}</ref>
* LTB4 treatment for smooth muscle cells makes the blood flow to target tissue (esp. heart) about 4 times more. LTB4 also increase the smooth muscle cells migration in response to chemotaxis.<ref name="pmid16293697">{{cite journal |vauthors=Bäck M, Bu DX, Bränström R, Sheikine Y, Yan ZQ, Hansson GK |title=Leukotriene B4 signaling through NF-kappaB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=102 |issue=48 |pages=17501–6 |year=2005 |pmid=16293697 |pmc=1297663 |doi=10.1073/pnas.0505845102 |url=}}</ref>
* [[Leukotriene B4|LTB4]] treatment for [[smooth muscle cells]] makes the [[blood flow]] to target tissue (esp. [[heart]]) about 4 times more. [[Leukotriene B4|LTB4]] also increase the [[smooth muscle cells]] migration in response to [[chemotaxis]].<ref name="pmid16293697">{{cite journal |vauthors=Bäck M, Bu DX, Bränström R, Sheikine Y, Yan ZQ, Hansson GK |title=Leukotriene B4 signaling through NF-kappaB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=102 |issue=48 |pages=17501–6 |year=2005 |pmid=16293697 |pmc=1297663 |doi=10.1073/pnas.0505845102 |url=}}</ref>


=== Prostaglandin E receptor 2 (PTGER2) gene ===
=== Prostaglandin E receptor 2 (PTGER2) gene ===
*Prostaglandin E receptor 2 (PTGER2) [[gene]] with [[OMIM]] number of 176804 is on [[chromosome]] 14q22.1. PTGER2 [[gene]] is responsible for various biological activities in diverse tissues.
*[[Prostaglandin E2 receptor|Prostaglandin E receptor 2 (PTGER2)]] [[gene]] with [[OMIM]] number of 176804 is on [[chromosome]] 14q22.1. [[Prostaglandin E2 receptor|PTGER2]] [[gene]] is responsible for various biological activities in diverse [[tissues]].
*It is postulated that PTGER2 gene expression is reduced in portal hypertension.<ref name="KotaniKawabe2015" />
*It is postulated that [[PTGER2]] [[gene expression]] is reduced in portal hypertension.<ref name="KotaniKawabe2015" />


=== Endothelin (EDN1) gene ===
=== Endothelin (EDN1) gene ===
*Endothelin (EDN1) [[gene]] with [[OMIM]] number of 131240 is on [[chromosome]] 6p24.1. EDN1 [[gene]] is responsible for vasoconstriction and is secreted from endothelium.
*[[Endothelin|Endothelin (EDN1)]] [[gene]] with [[OMIM]] number of 131240 is on [[chromosome]] 6p24.1. [[Endothelin 1|EDN1]] [[gene]] is responsible for [[vasoconstriction]] and is secreted from [[endothelium]].
*Endothelin is the most powerful vasoconstrictor known.<ref name="pmid2670930">{{cite journal |vauthors=Inoue A, Yanagisawa M, Takuwa Y, Mitsui Y, Kobayashi M, Masaki T |title=The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression |journal=J. Biol. Chem. |volume=264 |issue=25 |pages=14954–9 |year=1989 |pmid=2670930 |doi= |url=}}</ref>
*[[Endothelin]] is the most powerful [[vasoconstrictor]] known.<ref name="pmid2670930">{{cite journal |vauthors=Inoue A, Yanagisawa M, Takuwa Y, Mitsui Y, Kobayashi M, Masaki T |title=The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression |journal=J. Biol. Chem. |volume=264 |issue=25 |pages=14954–9 |year=1989 |pmid=2670930 |doi= |url=}}</ref>
*Increased expression of EDN1 is directly related to hypertension in patients.<ref name="pmid15148269">{{cite journal |vauthors=Campia U, Cardillo C, Panza JA |title=Ethnic differences in the vasoconstrictor activity of endogenous endothelin-1 in hypertensive patients |journal=Circulation |volume=109 |issue=25 |pages=3191–5 |year=2004 |pmid=15148269 |doi=10.1161/01.CIR.0000130590.24107.D3 |url=}}</ref>
*Increased [[Gene expression|expression]] of [[EDN1]] is directly related to [[hypertension]] in patients.<ref name="pmid15148269">{{cite journal |vauthors=Campia U, Cardillo C, Panza JA |title=Ethnic differences in the vasoconstrictor activity of endogenous endothelin-1 in hypertensive patients |journal=Circulation |volume=109 |issue=25 |pages=3191–5 |year=2004 |pmid=15148269 |doi=10.1161/01.CIR.0000130590.24107.D3 |url=}}</ref>


=== Endothelin receptor type A (EDNRA) gene ===
=== Endothelin receptor type A (EDNRA) gene ===
*Endothelin receptor type A (EDNRA) [[gene]] with [[OMIM]] number of 131243 is on [[chromosome]] 4q31.22-q31.23. EDNRA [[gene]] is responsible for vasoconstriction through binding to endothelin.  
*[[Endothelin receptor type A|Endothelin receptor type A (EDNRA)]] [[gene]] with [[OMIM]] number of 131243 is on [[chromosome]] 4q31.22-q31.23. [[Endothelin receptor type A|EDNRA]] [[gene]] is responsible for [[vasoconstriction]] through binding to [[endothelin]].  
*It is postulated that EDNRA gene expression is reduced in portal hypertension.<ref name="KotaniKawabe2015" />  
*It is postulated that [[Endothelin receptor type A|EDNRA]] [[gene]] expression is reduced in portal hypertension.<ref name="KotaniKawabe2015" />  
*Increased expression of EDNRA is directly related to hypertension in patients.<ref name="pmid15148269" />  
*Decreased [[Gene expression|expression]] of [[Endothelin receptor type A|EDNRA]] is directly related to [[hypertension]] in patients.<ref name="pmid15148269" />  


=== Natriuretic peptide receptor 3 (NPR3) gene ===
=== Natriuretic peptide receptor 3 (NPR3) gene ===
*Natriuretic peptide receptor 3 (NPR3) [[gene]] with [[OMIM]] number of 108962 is on [[chromosome]] 5p13.3. NPR3 [[gene]] is responsible for maintenance of blood pressure and extracellular fluid volume.  
*[[Natriuretic peptides|Natriuretic peptide receptor 3 (NPR3)]] [[gene]] with [[OMIM]] number of 108962 is on [[chromosome]] 5p13.3. NPR3 [[gene]] is responsible for maintenance of [[blood pressure]] and [[Extracellular fluid|extracellular fluid volume]].  
*It is postulated that NPR3 gene expression is elevated in portal hypertension.<ref name="KotaniKawabe2015" />  
*It is postulated that NPR3 [[gene expression]] is elevated in portal hypertension.<ref name="KotaniKawabe2015" />  
*Atrial natriuretic peptide (ANP) released from heart muscle in response to increase in wall tension. When ANP binds to NPR3, it can modulate blood pressure.<ref name="pmid7477288">{{cite journal |vauthors=Lopez MJ, Wong SK, Kishimoto I, Dubois S, Mach V, Friesen J, Garbers DL, Beuve A |title=Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide |journal=Nature |volume=378 |issue=6552 |pages=65–8 |year=1995 |pmid=7477288 |doi=10.1038/378065a0 |url=}}</ref>  
*[[Atrial natriuretic peptide|Atrial natriuretic peptide (ANP)]] released from [[heart muscle]] in response to increase in wall tension. When [[Atrial natriuretic peptide|ANP]] binds to NPR3, it can modulate [[blood pressure]].<ref name="pmid7477288">{{cite journal |vauthors=Lopez MJ, Wong SK, Kishimoto I, Dubois S, Mach V, Friesen J, Garbers DL, Beuve A |title=Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide |journal=Nature |volume=378 |issue=6552 |pages=65–8 |year=1995 |pmid=7477288 |doi=10.1038/378065a0 |url=}}</ref>  


=== Cluster of differentiation 44 (CD44) gene ===
=== Cluster of differentiation 44 (CD44) gene ===
*Cluster of differentiation 44 (CD44) [[gene]] with [[OMIM]] number of 107269 is on [[chromosome]] 11p13. CD44 [[gene]] is responsible for lymphocyte activation and lymph node homing.<ref name="pmid1694723">{{cite journal |vauthors=Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B |title=CD44 is the principal cell surface receptor for hyaluronate |journal=Cell |volume=61 |issue=7 |pages=1303–13 |year=1990 |pmid=1694723 |doi= |url=}}</ref>
*[[Cluster of differentiation|Cluster of differentiation 44 (CD44)]] [[gene]] with [[OMIM]] number of 107269 is on [[chromosome]] 11p13. [[CD44]] [[gene]] is responsible for [[lymphocyte]] activation and [[lymph node]] homing.<ref name="pmid1694723">{{cite journal |vauthors=Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B |title=CD44 is the principal cell surface receptor for hyaluronate |journal=Cell |volume=61 |issue=7 |pages=1303–13 |year=1990 |pmid=1694723 |doi= |url=}}</ref>
*It is postulated that CD44 gene expression is reduced in portal hypertension.<ref name="KotaniKawabe2015" />
*It is postulated that [[CD44]] [[gene expression]] is reduced in portal hypertension.<ref name="KotaniKawabe2015" />
*It is thought that CD44 is related to fibroblast growth factor (FGF) and can lead to fibrosis in various tissue.<ref name="pmid12697740">{{cite journal |vauthors=Nedvetzki S, Golan I, Assayag N, Gonen E, Caspi D, Gladnikoff M, Yayon A, Naor D |title=A mutation in a CD44 variant of inflammatory cells enhances the mitogenic interaction of FGF with its receptor |journal=J. Clin. Invest. |volume=111 |issue=8 |pages=1211–20 |year=2003 |pmid=12697740 |doi=10.1172/JCI17100 |url=}}</ref>
*It is thought that [[CD44]] is related to [[Fibroblast growth factor|fibroblast growth factor (FGF)]] and can lead to [[fibrosis]] in various [[tissue]].<ref name="pmid12697740">{{cite journal |vauthors=Nedvetzki S, Golan I, Assayag N, Gonen E, Caspi D, Gladnikoff M, Yayon A, Naor D |title=A mutation in a CD44 variant of inflammatory cells enhances the mitogenic interaction of FGF with its receptor |journal=J. Clin. Invest. |volume=111 |issue=8 |pages=1211–20 |year=2003 |pmid=12697740 |doi=10.1172/JCI17100 |url=}}</ref>
*CD44 expression is increased during collateral arteriogenesis in mice.<ref name="pmid15023889">{{cite journal |vauthors=van Royen N, Voskuil M, Hoefer I, Jost M, de Graaf S, Hedwig F, Andert JP, Wormhoudt TA, Hua J, Hartmann S, Bode C, Buschmann I, Schaper W, van der Neut R, Piek JJ, Pals ST |title=CD44 regulates arteriogenesis in mice and is differentially expressed in patients with poor and good collateralization |journal=Circulation |volume=109 |issue=13 |pages=1647–52 |year=2004 |pmid=15023889 |doi=10.1161/01.CIR.0000124066.35200.18 |url=}}</ref>
*[[CD44]] [[Gene expression|expression]] is increased during [[collateral]] [[arteriogenesis]] in mice.<ref name="pmid15023889">{{cite journal |vauthors=van Royen N, Voskuil M, Hoefer I, Jost M, de Graaf S, Hedwig F, Andert JP, Wormhoudt TA, Hua J, Hartmann S, Bode C, Buschmann I, Schaper W, van der Neut R, Piek JJ, Pals ST |title=CD44 regulates arteriogenesis in mice and is differentially expressed in patients with poor and good collateralization |journal=Circulation |volume=109 |issue=13 |pages=1647–52 |year=2004 |pmid=15023889 |doi=10.1161/01.CIR.0000124066.35200.18 |url=}}</ref>


=== Transforming growth factor (TGF)-β gene ===
=== Transforming growth factor (TGF)-β gene ===
*Transforming growth factor (TGF)-β [[gene]] with [[OMIM]] number of 190180 is on [[chromosome]] 19q13.2. TGF-β [[gene]] is responsible for tissue transformation and its dysregulation may lead to apoptosis.<ref name="pmid11586292">{{cite journal |vauthors=Derynck R, Akhurst RJ, Balmain A |title=TGF-beta signaling in tumor suppression and cancer progression |journal=Nat. Genet. |volume=29 |issue=2 |pages=117–29 |year=2001 |pmid=11586292 |doi=10.1038/ng1001-117 |url=}}</ref>
*[[Transforming growth factor-β|Transforming growth factor (TGF)-β]] [[gene]] with [[OMIM]] number of 190180 is on [[chromosome]] 19q13.2. [[TGF-β]] [[gene]] is responsible for tissue [[transformation]] and its dysregulation may lead to [[apoptosis]].<ref name="pmid11586292">{{cite journal |vauthors=Derynck R, Akhurst RJ, Balmain A |title=TGF-beta signaling in tumor suppression and cancer progression |journal=Nat. Genet. |volume=29 |issue=2 |pages=117–29 |year=2001 |pmid=11586292 |doi=10.1038/ng1001-117 |url=}}</ref>
*It is postulated that TGF-β gene expression is reduced in portal hypertension.<ref name="KotaniKawabe2015" />
*It is postulated that [[TGF-β]] [[gene expression]] is reduced in portal hypertension.<ref name="KotaniKawabe2015" />
*TGF-β is hyper-expressed in African-American hypertensive patients.<ref name="pmid10725360">{{cite journal |vauthors=Suthanthiran M, Li B, Song JO, Ding R, Sharma VK, Schwartz JE, August P |title=Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue=7 |pages=3479–84 |year=2000 |pmid=10725360 |pmc=16265 |doi=10.1073/pnas.050420897 |url=}}</ref>
*[[TGF-β]] is hyper-expressed in African-American [[Hypertension|hypertensive]] patients.<ref name="pmid10725360">{{cite journal |vauthors=Suthanthiran M, Li B, Song JO, Ding R, Sharma VK, Schwartz JE, August P |title=Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue=7 |pages=3479–84 |year=2000 |pmid=10725360 |pmc=16265 |doi=10.1073/pnas.050420897 |url=}}</ref>


=== Ectonucleoside triphosphate diphosphohydrolase 4 (ENTPD4) gene ===
=== Ectonucleoside triphosphate diphosphohydrolase 4 (ENTPD4) gene ===
* Ectonucleoside triphosphate diphosphohydrolase 4 (ENTPD4) [[gene]] with [[OMIM]] number of 607577 is on [[chromosome]] 8p21.3. ENTPD4 [[gene]] is responsible for increasing phosphatase activity in intracellular membrane-bound nucleosides.
* Ectonucleoside triphosphate diphosphohydrolase 4 (ENTPD4) [[gene]] with [[OMIM]] number of 607577 is on [[chromosome]] 8p21.3. [[ENTPD6|ENTPD4]] [[gene]] is responsible for increasing [[phosphatase]] activity in [[intracellular]] membrane-bound [[nucleosides]].
* It is postulated that TGF-β gene expression is reduced in portal hypertension.<ref name="KotaniKawabe2015" />
* It is postulated that [[TGF-β]] [[gene expression]] is reduced in portal hypertension.<ref name="KotaniKawabe2015" />


=== ATP-binding cassette, subfamily C, member 1 (ABCC1) gene ===
=== ATP-binding cassette, subfamily C, member 1 (ABCC1) gene ===
* ATP-binding cassette, subfamily C, member 1 (ABCC1) [[gene]] with [[OMIM]] number of 158343 is on [[chromosome]] 16p13.11. ABCC1 [[gene]] is responsible for multi-drug resistance in small cell lung cancer.<ref name="pmid1360704">{{cite journal |vauthors=Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG |title=Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line |journal=Science |volume=258 |issue=5088 |pages=1650–4 |year=1992 |pmid=1360704 |doi= |url=}}</ref>
* [[ABCC1|ATP-binding cassette, subfamily C, member 1 (ABCC1)]] [[gene]] with [[OMIM]] number of 158343 is on [[chromosome]] 16p13.11. [[ABCC1]] [[gene]] is responsible for [[Multidrug resistance|multi-drug resistance]] in [[small cell lung cancer]].<ref name="pmid1360704">{{cite journal |vauthors=Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG |title=Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line |journal=Science |volume=258 |issue=5088 |pages=1650–4 |year=1992 |pmid=1360704 |doi= |url=}}</ref>
* It is postulated that ABCC1 gene expression is reduced in portal hypertension.<ref name="KotaniKawabe2015" />
* It is postulated that [[ABCC1]] [[gene expression]] is reduced in portal hypertension.<ref name="KotaniKawabe2015" />


==Associated Conditions==
==Associated Conditions==
=== Immunological disorders ===
* [[Common variable immunodeficiency|Common variable immunodeficiency syndrome]]<ref name="pmid23420139">{{cite journal |vauthors=Fuss IJ, Friend J, Yang Z, He JP, Hooda L, Boyer J, Xi L, Raffeld M, Kleiner DE, Heller T, Strober W |title=Nodular regenerative hyperplasia in common variable immunodeficiency |journal=J. Clin. Immunol. |volume=33 |issue=4 |pages=748–58 |year=2013 |pmid=23420139 |pmc=3731765 |doi=10.1007/s10875-013-9873-6 |url=}}</ref>
* [[Connective tissue disease|Connective tissue diseases]]<ref name="pmid21393872">{{cite journal |vauthors=Vaiphei K, Bhatia A, Sinha SK |title=Liver pathology in collagen vascular disorders highlighting the vascular changes within portal tracts |journal=Indian J Pathol Microbiol |volume=54 |issue=1 |pages=25–31 |year=2011 |pmid=21393872 |doi=10.4103/0377-4929.77319 |url=}}</ref>
* [[Crohn’s disease]]<ref name="pmid18415755">{{cite journal |vauthors=De Boer NK, Tuynman H, Bloemena E, Westerga J, Van Der Peet DL, Mulder CJ, Cuesta MA, Meuwissen SG, Van Nieuwkerk CM, Van Bodegraven AA |title=Histopathology of liver biopsies from a thiopurine-naïve inflammatory bowel disease cohort: prevalence of nodular regenerative hyperplasia |journal=Scand. J. Gastroenterol. |volume=43 |issue=5 |pages=604–8 |year=2008 |pmid=18415755 |doi=10.1080/00365520701800266 |url=}}</ref>
* [[Organ transplant|Solid organ transplant]]
** [[Renal transplantation]]<ref name="pmid1438671">{{cite journal |vauthors=Allison MC, Mowat A, McCruden EA, McGregor E, Burt AD, Briggs JD, Junor BJ, Follett EA, MacSween RN, Mills PR |title=The spectrum of chronic liver disease in renal transplant recipients |journal=Q. J. Med. |volume=83 |issue=301 |pages=355–67 |year=1992 |pmid=1438671 |doi= |url=}}</ref>
** [[Liver transplantation]]<ref name="pmid8020909">{{cite journal |vauthors=Gane E, Portmann B, Saxena R, Wong P, Ramage J, Williams R |title=Nodular regenerative hyperplasia of the liver graft after liver transplantation |journal=Hepatology |volume=20 |issue=1 Pt 1 |pages=88–94 |year=1994 |pmid=8020909 |doi= |url=}}</ref>
* [[Hashimoto's thyroiditis]]<ref name="pmid2944377">{{cite journal |vauthors=Imai Y, Minami Y, Miyoshi S, Kawata S, Saito R, Noda S, Tamura S, Nishikawa M, Tajima K, Tarui S |title=Idiopathic portal hypertension associated with Hashimoto's disease: report of three cases |journal=Am. J. Gastroenterol. |volume=81 |issue=9 |pages=791–5 |year=1986 |pmid=2944377 |doi= |url=}}</ref>
* [[Autoimmune disease]]<ref name="pmid11831999">{{cite journal |vauthors=Li X, Gao W, Chen J, Tang W |title=[Non-cirrhotic portal hypertension associated with autoimmune disease] |language=Chinese |journal=Zhonghua Wai Ke Za Zhi |volume=38 |issue=2 |pages=101–3 |year=2000 |pmid=11831999 |doi= |url=}}</ref>
=== Infections ===
* [[Bacterial]] intestinal [[Infection|infections]]
** Recurrent [[Escherichia coli|E.coli]] infection<ref name="pmid3276575">{{cite journal |vauthors=Kono K, Ohnishi K, Omata M, Saito M, Nakayama T, Hatano H, Nakajima Y, Sugita S, Okuda K |title=Experimental portal fibrosis produced by intraportal injection of killed nonpathogenic Escherichia coli in rabbits |journal=Gastroenterology |volume=94 |issue=3 |pages=787–96 |year=1988 |pmid=3276575 |doi= |url=}}</ref>
* [[Human Immunodeficiency Virus (HIV)|Human immunodeficiency virus (HIV) infection]]<ref name="pmid24155091">{{cite journal |vauthors=Siramolpiwat S, Seijo S, Miquel R, Berzigotti A, Garcia-Criado A, Darnell A, Turon F, Hernandez-Gea V, Bosch J, Garcia-Pagán JC |title=Idiopathic portal hypertension: natural history and long-term outcome |journal=Hepatology |volume=59 |issue=6 |pages=2276–85 |year=2014 |pmid=24155091 |doi=10.1002/hep.26904 |url=}}</ref>
* [[AIDS antiretroviral drugs|Antiretroviral therapy]]<ref name="pmid18389904">{{cite journal |vauthors=Maida I, Garcia-Gasco P, Sotgiu G, Rios MJ, Vispo ME, Martin-Carbonero L, Barreiro P, Mura MS, Babudieri S, Albertos S, Garcia-Samaniego J, Soriano V |title=Antiretroviral-associated portal hypertension: a new clinical condition? Prevalence, predictors and outcome |journal=Antivir. Ther. (Lond.) |volume=13 |issue=1 |pages=103–7 |year=2008 |pmid=18389904 |doi= |url=}}</ref>
=== Medication and toxins ===
* [[Thiopurine|Thiopurine derivatives]]
** [[Didanosine]]
** [[Azathioprine]]<ref name="pmid17504943">{{cite journal |vauthors=Vernier-Massouille G, Cosnes J, Lemann M, Marteau P, Reinisch W, Laharie D, Cadiot G, Bouhnik Y, De Vos M, Boureille A, Duclos B, Seksik P, Mary JY, Colombel JF |title=Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine |journal=Gut |volume=56 |issue=10 |pages=1404–9 |year=2007 |pmid=17504943 |pmc=2000290 |doi=10.1136/gut.2006.114363 |url=}}</ref>
** [[Thioguanine|Cis-thioguanine]]<ref name="pmid21272804">{{cite journal |vauthors=Calabrese E, Hanauer SB |title=Assessment of non-cirrhotic portal hypertension associated with thiopurine therapy in inflammatory bowel disease |journal=J Crohns Colitis |volume=5 |issue=1 |pages=48–53 |year=2011 |pmid=21272804 |doi=10.1016/j.crohns.2010.08.007 |url=}}</ref>
* [[Arsenicals]]<ref name="pmid2398270">{{cite journal |vauthors=Nevens F, Fevery J, Van Steenbergen W, Sciot R, Desmet V, De Groote J |title=Arsenic and non-cirrhotic portal hypertension. A report of eight cases |journal=J. Hepatol. |volume=11 |issue=1 |pages=80–5 |year=1990 |pmid=2398270 |doi= |url=}}</ref>
* [[Vitamin A]]<ref name="pmid2019375">{{cite journal |vauthors=Geubel AP, De Galocsy C, Alves N, Rahier J, Dive C |title=Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases |journal=Gastroenterology |volume=100 |issue=6 |pages=1701–9 |year=1991 |pmid=2019375 |doi= |url=}}</ref>
=== Genetic disorders ===
* Adams-Olivier syndrome<ref name="pmid15832360">{{cite journal |vauthors=Girard M, Amiel J, Fabre M, Pariente D, Lyonnet S, Jacquemin E |title=Adams-Oliver syndrome and hepatoportal sclerosis: occasional association or common mechanism? |journal=Am. J. Med. Genet. A |volume=135 |issue=2 |pages=186–9 |year=2005 |pmid=15832360 |doi=10.1002/ajmg.a.30724 |url=}}</ref>
* [[Turner syndrome]]<ref name="pmid23121401">{{cite journal |vauthors=Roulot D |title=Liver involvement in Turner syndrome |journal=Liver Int. |volume=33 |issue=1 |pages=24–30 |year=2013 |pmid=23121401 |doi=10.1111/liv.12007 |url=}}</ref>
* Phosphomannose isomerase deficiency<ref name="pmid19101627">{{cite journal |vauthors=de Lonlay P, Seta N |title=The clinical spectrum of phosphomannose isomerase deficiency, with an evaluation of mannose treatment for CDG-Ib |journal=Biochim. Biophys. Acta |volume=1792 |issue=9 |pages=841–3 |year=2009 |pmid=19101627 |doi=10.1016/j.bbadis.2008.11.012 |url=}}</ref>
* Familial cases<ref name="pmid3499813">{{cite journal |vauthors=Sarin SK, Mehra NK, Agarwal A, Malhotra V, Anand BS, Taneja V |title=Familial aggregation in noncirrhotic portal fibrosis: a report of four families |journal=Am. J. Gastroenterol. |volume=82 |issue=11 |pages=1130–3 |year=1987 |pmid=3499813 |doi= |url=}}</ref>
=== Prothrombotic conditions ===
* [[Inherited thrombophilia|Inherited thrombophilias]] <ref name="pmid18685811">{{cite journal |vauthors=Bayan K, Tüzün Y, Yilmaz S, Canoruc N, Dursun M |title=Analysis of inherited thrombophilic mutations and natural anticoagulant deficiency in patients with idiopathic portal hypertension |journal=J. Thromb. Thrombolysis |volume=28 |issue=1 |pages=57–62 |year=2009 |pmid=18685811 |doi=10.1007/s11239-008-0244-8 |url=}}</ref>
* [[Myeloproliferative neoplasm]]<ref name="pmid18685811" />
* [[Antiphospholipid syndrome]]<ref name="pmid18685811" />
* [[Sickle cell disease]]<ref name="pmid17558079">{{cite journal |vauthors=Kumar S, Joshi R, Jain AP |title=Portal hypertension associated with sickle cell disease |journal=Indian J Gastroenterol |volume=26 |issue=2 |pages=94 |year=2007 |pmid=17558079 |doi= |url=}}</ref>
==Gross Pathology==
==Gross Pathology==
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Revision as of 14:12, 26 October 2017

Portal Hypertension Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Portal Hypertension from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Echocardiography and Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Portal hypertension pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Portal hypertension pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Portal hypertension pathophysiology

CDC on Portal hypertension pathophysiology

Portal hypertension pathophysiology in the news

Blogs on Portal hypertension pathophysiology

Directions to Hospitals Treating Portal hypertension

Risk calculators and risk factors for Portal hypertension pathophysiology

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

Physiology

  • 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; π=22/7
  • 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>



 
 
• 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

Hyperdynamic circulation in portal hypertension

Genetics

Gene OMIM number Chromosome Function Gene expression in portal hypertension Notes
Deoxyguanosine kinase (DGUOK) 601465 2p13.1 DNA replication Point mutation Mutation leads to:
Adenosine deaminase (ADA) 608958 20q13.12 Irreversible deamination of adenosine and deoxyadenosine Reduced Some roles in modulating tissue response to IL-13

The main effects of IL-13 are:

Phospholipase A2 (PL2G10) 603603 16p13.12 Catalyzing the release of fatty acids from phospholipids Reduced Identifier of PL2G10 expression:
Cytochrome P450, family 4, subfamily F, polypeptide 3 (CYP4F3) 601270 19p13.12 Catalyzing the omega-hydroxylation of leukotriene B4 (LTB4) Increased -
Glutathione peroxidase 3 (GPX3) 138321 5q33.1 Glutathione reduction which reduce: Increased Protects various organs against oxidative stress:
Leukotriene B4 (LTB4) 601531 14q12 Mutated Increase blood flow to target tissue (esp. heart) about 4 times more.
Prostaglandin E receptor 2 (PTGER2) 176804 14q22.1 Various biological activities in diverse tissues Reduced -
Endothelin (EDN1) 131240 6p24.1 Vasoconstriction Increased The most powerful vasoconstrictor known
Endothelin receptor type A (EDNRA) 131243 4q31.22-q31.23 Vasoconstriction through binding to endothelin Reduced Directly related to hypertension in patients
Natriuretic peptide receptor 3 (NPR3) 108962 5p13.3 Maintenance of: Increased Released from heart muscle in response to increase in wall tension
Cluster of differentiation 44 (CD44) 107269 11p13 Reduced
Transforming growth factor (TGF)-β 190180 19q13.2 Reduced Hyper-expressed in African-American hypertensive patients
Ectonucleoside triphosphate diphosphohydrolase 4 (ENTPD4) 607577 8p21.3 Increasing phosphatase activity in intracellular membrane-bound nucleosides Reduced -
ATP-binding cassette, subfamily C, member 1 (ABCC1) 158343 16p13.11 Multi-drug resistance in small cell lung cancer Reduced -

Deoxyguanosine kinase (DGUOK) gene

Adenosine deaminase (ADA) gene

Phospholipase A2 (PL2G10) gene

Cytochrome P450, family 4, subfamily F, polypeptide 3 (CYP4F3) gene

Glutathione peroxidase 3 (GPX3) gene

Leukotriene B4 (LTB4) gene

Prostaglandin E receptor 2 (PTGER2) gene

Endothelin (EDN1) gene

Endothelin receptor type A (EDNRA) gene

Natriuretic peptide receptor 3 (NPR3) gene

Cluster of differentiation 44 (CD44) gene

Transforming growth factor (TGF)-β gene

Ectonucleoside triphosphate diphosphohydrolase 4 (ENTPD4) gene

ATP-binding cassette, subfamily C, member 1 (ABCC1) gene

Associated Conditions

Immunological disorders

Infections

Medication and toxins

Genetic disorders

Prothrombotic 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

  1. ↑ Greenway CV, Stark RD (1971). "Hepatic vascular bed". Physiol. Rev. 51 (1): 23–65. PMID 5543903.
  2. ↑ Schiff, Eugene (2012). Schiff's diseases of the liver. Chichester, West Sussex, UK: John Wiley & Sons. ISBN 9780470654682.
  3. ↑ 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.
  4. ↑ SCHAFFNER F, POPER H (1963). "Capillarization of hepatic sinusoids in man". Gastroenterology. 44: 239–42. PMID 13976646.
  5. ↑ Reynolds TB, Hidemura R, Michel H, Peters R (1969). "Portal hypertension without cirrhosis in alcoholic liver disease". Ann. Intern. Med. 70 (3): 497–506. PMID 5775031.
  6. ↑ Rubanyi GM (1991). "Endothelium-derived relaxing and contracting factors". J. Cell. Biochem. 46 (1): 27–36. doi:10.1002/jcb.240460106. PMID 1874796.
  7. ↑ Epstein, Franklin H.; Vane, John R.; Änggård, Erik E.; Botting, Regina M. (1990). "Regulatory Functions of the Vascular Endothelium". New England Journal of Medicine. 323 (1): 27–36. doi:10.1056/NEJM199007053230106. ISSN 0028-4793.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ Colombato LA, Albillos A, Groszmann RJ (1992). "Temporal relationship of peripheral vasodilatation, plasma volume expansion and the hyperdynamic circulatory state in portal-hypertensive rats". Hepatology. 15 (2): 323–8. PMID 1735537.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ Mandel H, Szargel R, Labay V, Elpeleg O, Saada A, Shalata A, Anbinder Y, Berkowitz D, Hartman C, Barak M, Eriksson S, Cohen N (2001). "The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA". Nat. Genet. 29 (3): 337–41. doi:10.1038/ng746. PMID 11687800.
  16. ↑ Vilarinho S, Sari S, Yilmaz G, Stiegler AL, Boggon TJ, Jain D, Akyol G, Dalgic B, Günel M, Lifton RP (2016). "Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension". Hepatology. 63 (6): 1977–86. doi:10.1002/hep.28499. PMC 4874872. PMID 26874653.
  17. ↑ 17.00 17.01 17.02 17.03 17.04 17.05 17.06 17.07 17.08 17.09 17.10 Kotani, Kohei; Kawabe, Joji; Morikawa, Hiroyasu; Akahoshi, Tomohiko; Hashizume, Makoto; Shiomi, Susumu (2015). "Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension". Mediators of Inflammation. 2015: 1–10. doi:10.1155/2015/349215. ISSN 0962-9351.
  18. ↑ Blackburn MR, Lee CG, Young HW, Zhu Z, Chunn JL, Kang MJ, Banerjee SK, Elias JA (2003). "Adenosine mediates IL-13-induced inflammation and remodeling in the lung and interacts in an IL-13-adenosine amplification pathway". J. Clin. Invest. 112 (3): 332–44. doi:10.1172/JCI16815. PMC 166289. PMID 12897202.
  19. ↑ Chambers I, Frampton J, Goldfarb P, Affara N, McBain W, Harrison PR (1986). "The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the 'termination' codon, TGA". EMBO J. 5 (6): 1221–7. PMC 1166931. PMID 3015592.
  20. ↑ Chu FF, Esworthy RS, Doroshow JH, Doan K, Liu XF (1992). "Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents". Blood. 79 (12): 3233–8. PMID 1339300.
  21. ↑ Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T (1997). "A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis". Nature. 387 (6633): 620–4. doi:10.1038/42506. PMID 9177352.
  22. ↑ Bäck M, Bu DX, Bränström R, Sheikine Y, Yan ZQ, Hansson GK (2005). "Leukotriene B4 signaling through NF-kappaB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia". Proc. Natl. Acad. Sci. U.S.A. 102 (48): 17501–6. doi:10.1073/pnas.0505845102. PMC 1297663. PMID 16293697.
  23. ↑ Inoue A, Yanagisawa M, Takuwa Y, Mitsui Y, Kobayashi M, Masaki T (1989). "The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression". J. Biol. Chem. 264 (25): 14954–9. PMID 2670930.
  24. ↑ 24.0 24.1 Campia U, Cardillo C, Panza JA (2004). "Ethnic differences in the vasoconstrictor activity of endogenous endothelin-1 in hypertensive patients". Circulation. 109 (25): 3191–5. doi:10.1161/01.CIR.0000130590.24107.D3. PMID 15148269.
  25. ↑ Lopez MJ, Wong SK, Kishimoto I, Dubois S, Mach V, Friesen J, Garbers DL, Beuve A (1995). "Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide". Nature. 378 (6552): 65–8. doi:10.1038/378065a0. PMID 7477288.
  26. ↑ Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B (1990). "CD44 is the principal cell surface receptor for hyaluronate". Cell. 61 (7): 1303–13. PMID 1694723.
  27. ↑ Nedvetzki S, Golan I, Assayag N, Gonen E, Caspi D, Gladnikoff M, Yayon A, Naor D (2003). "A mutation in a CD44 variant of inflammatory cells enhances the mitogenic interaction of FGF with its receptor". J. Clin. Invest. 111 (8): 1211–20. doi:10.1172/JCI17100. PMID 12697740.
  28. ↑ van Royen N, Voskuil M, Hoefer I, Jost M, de Graaf S, Hedwig F, Andert JP, Wormhoudt TA, Hua J, Hartmann S, Bode C, Buschmann I, Schaper W, van der Neut R, Piek JJ, Pals ST (2004). "CD44 regulates arteriogenesis in mice and is differentially expressed in patients with poor and good collateralization". Circulation. 109 (13): 1647–52. doi:10.1161/01.CIR.0000124066.35200.18. PMID 15023889.
  29. ↑ Derynck R, Akhurst RJ, Balmain A (2001). "TGF-beta signaling in tumor suppression and cancer progression". Nat. Genet. 29 (2): 117–29. doi:10.1038/ng1001-117. PMID 11586292.
  30. ↑ Suthanthiran M, Li B, Song JO, Ding R, Sharma VK, Schwartz JE, August P (2000). "Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3479–84. doi:10.1073/pnas.050420897. PMC 16265. PMID 10725360.
  31. ↑ Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG (1992). "Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line". Science. 258 (5088): 1650–4. PMID 1360704.
  32. ↑ Fuss IJ, Friend J, Yang Z, He JP, Hooda L, Boyer J, Xi L, Raffeld M, Kleiner DE, Heller T, Strober W (2013). "Nodular regenerative hyperplasia in common variable immunodeficiency". J. Clin. Immunol. 33 (4): 748–58. doi:10.1007/s10875-013-9873-6. PMC 3731765. PMID 23420139.
  33. ↑ Vaiphei K, Bhatia A, Sinha SK (2011). "Liver pathology in collagen vascular disorders highlighting the vascular changes within portal tracts". Indian J Pathol Microbiol. 54 (1): 25–31. doi:10.4103/0377-4929.77319. PMID 21393872.
  34. ↑ De Boer NK, Tuynman H, Bloemena E, Westerga J, Van Der Peet DL, Mulder CJ, Cuesta MA, Meuwissen SG, Van Nieuwkerk CM, Van Bodegraven AA (2008). "Histopathology of liver biopsies from a thiopurine-naïve inflammatory bowel disease cohort: prevalence of nodular regenerative hyperplasia". Scand. J. Gastroenterol. 43 (5): 604–8. doi:10.1080/00365520701800266. PMID 18415755.
  35. ↑ Allison MC, Mowat A, McCruden EA, McGregor E, Burt AD, Briggs JD, Junor BJ, Follett EA, MacSween RN, Mills PR (1992). "The spectrum of chronic liver disease in renal transplant recipients". Q. J. Med. 83 (301): 355–67. PMID 1438671.
  36. ↑ Gane E, Portmann B, Saxena R, Wong P, Ramage J, Williams R (1994). "Nodular regenerative hyperplasia of the liver graft after liver transplantation". Hepatology. 20 (1 Pt 1): 88–94. PMID 8020909.
  37. ↑ Imai Y, Minami Y, Miyoshi S, Kawata S, Saito R, Noda S, Tamura S, Nishikawa M, Tajima K, Tarui S (1986). "Idiopathic portal hypertension associated with Hashimoto's disease: report of three cases". Am. J. Gastroenterol. 81 (9): 791–5. PMID 2944377.
  38. ↑ Li X, Gao W, Chen J, Tang W (2000). "[Non-cirrhotic portal hypertension associated with autoimmune disease]". Zhonghua Wai Ke Za Zhi (in Chinese). 38 (2): 101–3. PMID 11831999.
  39. ↑ Kono K, Ohnishi K, Omata M, Saito M, Nakayama T, Hatano H, Nakajima Y, Sugita S, Okuda K (1988). "Experimental portal fibrosis produced by intraportal injection of killed nonpathogenic Escherichia coli in rabbits". Gastroenterology. 94 (3): 787–96. PMID 3276575.
  40. ↑ Siramolpiwat S, Seijo S, Miquel R, Berzigotti A, Garcia-Criado A, Darnell A, Turon F, Hernandez-Gea V, Bosch J, Garcia-Pagán JC (2014). "Idiopathic portal hypertension: natural history and long-term outcome". Hepatology. 59 (6): 2276–85. doi:10.1002/hep.26904. PMID 24155091.
  41. ↑ Maida I, Garcia-Gasco P, Sotgiu G, Rios MJ, Vispo ME, Martin-Carbonero L, Barreiro P, Mura MS, Babudieri S, Albertos S, Garcia-Samaniego J, Soriano V (2008). "Antiretroviral-associated portal hypertension: a new clinical condition? Prevalence, predictors and outcome". Antivir. Ther. (Lond.). 13 (1): 103–7. PMID 18389904.
  42. ↑ Vernier-Massouille G, Cosnes J, Lemann M, Marteau P, Reinisch W, Laharie D, Cadiot G, Bouhnik Y, De Vos M, Boureille A, Duclos B, Seksik P, Mary JY, Colombel JF (2007). "Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine". Gut. 56 (10): 1404–9. doi:10.1136/gut.2006.114363. PMC 2000290. PMID 17504943.
  43. ↑ Calabrese E, Hanauer SB (2011). "Assessment of non-cirrhotic portal hypertension associated with thiopurine therapy in inflammatory bowel disease". J Crohns Colitis. 5 (1): 48–53. doi:10.1016/j.crohns.2010.08.007. PMID 21272804.
  44. ↑ Nevens F, Fevery J, Van Steenbergen W, Sciot R, Desmet V, De Groote J (1990). "Arsenic and non-cirrhotic portal hypertension. A report of eight cases". J. Hepatol. 11 (1): 80–5. PMID 2398270.
  45. ↑ Geubel AP, De Galocsy C, Alves N, Rahier J, Dive C (1991). "Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases". Gastroenterology. 100 (6): 1701–9. PMID 2019375.
  46. ↑ Girard M, Amiel J, Fabre M, Pariente D, Lyonnet S, Jacquemin E (2005). "Adams-Oliver syndrome and hepatoportal sclerosis: occasional association or common mechanism?". Am. J. Med. Genet. A. 135 (2): 186–9. doi:10.1002/ajmg.a.30724. PMID 15832360.
  47. ↑ Roulot D (2013). "Liver involvement in Turner syndrome". Liver Int. 33 (1): 24–30. doi:10.1111/liv.12007. PMID 23121401.
  48. ↑ de Lonlay P, Seta N (2009). "The clinical spectrum of phosphomannose isomerase deficiency, with an evaluation of mannose treatment for CDG-Ib". Biochim. Biophys. Acta. 1792 (9): 841–3. doi:10.1016/j.bbadis.2008.11.012. PMID 19101627.
  49. ↑ Sarin SK, Mehra NK, Agarwal A, Malhotra V, Anand BS, Taneja V (1987). "Familial aggregation in noncirrhotic portal fibrosis: a report of four families". Am. J. Gastroenterol. 82 (11): 1130–3. PMID 3499813.
  50. ↑ 50.0 50.1 50.2 Bayan K, Tüzün Y, Yilmaz S, Canoruc N, Dursun M (2009). "Analysis of inherited thrombophilic mutations and natural anticoagulant deficiency in patients with idiopathic portal hypertension". J. Thromb. Thrombolysis. 28 (1): 57–62. doi:10.1007/s11239-008-0244-8. PMID 18685811.
  51. ↑ Kumar S, Joshi R, Jain AP (2007). "Portal hypertension associated with sickle cell disease". Indian J Gastroenterol. 26 (2): 94. PMID 17558079.

Template:WS Template:WH

Retrieved from "https://www.wikidoc.org/index.php?title=Portal_hypertension_pathophysiology&oldid=1379994"