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=== Physiology ===
=== Physiology ===
* [[Ohm's law]] in vascular system defines the [[pressure gradient]] (ΔP) in [[blood vessels]] as equal to product of [[Blood flow|blood flow (Q)]] and [[Vascular resistance|vascular resistance (R)]]:<math display="block">\Delta P =P2-P1= Q\times R</math>
* [[Ohm's law]] in vascular system defines the [[pressure gradient]] (ΔP) in [[blood vessels]] as equal to product of [[Blood flow|blood flow (Q)]] and [[Vascular resistance|vascular resistance (R)]]:
<br>
<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><small>η= [[Viscosity index|Viscosity]]; L= Length of [[vessel]]; r= Radius of [[vessel]]; π=22/7</small>
* Vascular resistance (R) has to be measured through Pouseuille’s law formula:
<br>
<math display="block">R = {8 \eta L\over \pi r^4}</math><small>η= [[Viscosity index|Viscosity]]; L= Length of [[vessel]]; r= Radius of [[vessel]]; π=22/7</small>


* When the (R) measurement formula is integrated in [[Ohm's law]] it becomes as the following:
* When the (R) measurement formula is integrated in [[Ohm's law]] it becomes as the following:
<br>
<math display="block">\Delta P= P_2-P_1 = {Q\times 8 \eta L\over \pi r^4}</math>
<math display="block">\Delta P= P_2-P_1 = {Q\times 8 \eta L\over \pi r^4}</math>


Line 290: Line 295:
{| align="right"
{| align="right"
|
|
[[image:Cirrosi micronodular.1427.jpg|thumb|300px|Micronodular cirrhosis - By Amadalvarez (Own work), via Wikimedia Commons<ref><CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)></ref>]]
[[image:Cirrosi micronodular.1427.jpg|thumb|350px|Micronodular cirrhosis - By Amadalvarez (Own work), via Wikimedia Commons<ref><CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)></ref>]]
|[[image:Fig78x.jpg|thumb|300px|Macronodular cirrhosis<ref name="urlwww.meddean.luc.edu">{{cite web |url=http://www.meddean.luc.edu/lumen/MedEd/orfpath/images/fig78x.jpg |title=www.meddean.luc.edu |format= |work= |accessdate=}}</ref>]]
|[[image:Fig78x.jpg|thumb|300px|Macronodular cirrhosis<ref name="urlwww.meddean.luc.edu">{{cite web |url=http://www.meddean.luc.edu/lumen/MedEd/orfpath/images/fig78x.jpg |title=www.meddean.luc.edu |format= |work= |accessdate=}}</ref>]]
[[image:Esplenomegalia i hiperplasia linfoide folicular reactiva. IMG 2865.jpg|thumb|300px|Splenomegaly - By Amadalvarez (Own work), via Wikimedia Commons<ref>Amadalvarez - <span class="int-own-work" lang="en">Own work</span>, <"https://creativecommons.org/licenses/by-sa/4.0" title="Creative Commons Attribution-Share Alike 4.0">CC BY-SA 4.0, <"https://commons.wikimedia.org/w/index.php?curid=49669333">Link</ref>]]
[[image:Esplenomegalia i hiperplasia linfoide folicular reactiva. IMG 2865.jpg|thumb|300px|Splenomegaly - By Amadalvarez (Own work), via Wikimedia Commons<ref>Amadalvarez - <span class="int-own-work" lang="en">Own work</span>, <"https://creativecommons.org/licenses/by-sa/4.0" title="Creative Commons Attribution-Share Alike 4.0">CC BY-SA 4.0, <"https://commons.wikimedia.org/w/index.php?curid=49669333">Link</ref>]]
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==Microscopic Pathology==
==Microscopic Pathology==
{| align="right"
|
[[image:Cirrhosis.jpg|thumb|375px|Cirrhosis with bridging fibrosis (yellow arrow) and nodule (black arrow) - By Nephron, via Librepathology.org<ref name="urlFile:Cirrhosis high mag.jpg - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/File:Cirrhosis_high_mag.jpg#filelinks |title=File:Cirrhosis high mag.jpg - Libre Pathology |format= |work= |accessdate=}}</ref>]]
[[image:Amyloidosis - high mag.jpg|thumb|375px|Hepatic amyloidosis with amorphous amyloids (black arrow) and normal hepatocytes (blue arrow), via Librepathology.org<ref name="urlFile:Hepatic amyloidosis - high mag.jpg - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/File:Hepatic_amyloidosis_-_high_mag.jpg |title=File:Hepatic amyloidosis - high mag.jpg - Libre Pathology |format= |work= |accessdate=}}</ref>]]
|
[[image:Congestive hepatopathy.jpg|thumb|300x250px|Congestive hepatopathy with central vein (yellow arrowhead), inflammatory cells, Councilman body (green arrowhead), and hepatocyte with mitotic figure (red arrowhead), via Librepathology.org<ref name="urlFile:2 CEN NEC 1 680x512px.tif - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/File:2_CEN_NEC_1_680x512px.tif |title=File:2 CEN NEC 1 680x512px.tif - Libre Pathology |format= |work= |accessdate=}}</ref>]]
[[image:Eso-varices.jpg|thumb|300px|Esophageal varices with submucosal vein (black arrow), via Librepathology.org<ref name="urlEsophageal varices - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/Esophageal_varices#cite_note-3 |title=Esophageal varices - Libre Pathology |format= |work= |accessdate=}}</ref>]]
|}
*The main microscopic [[histopathological]] findings in portal hypertension are related to [[Cirrhosis (patient information)|cirrhosis]], [[esophageal varices]], [[Hepatic amyloidosis with intrahepatic cholestasis|hepatic amyloidosis]], and congestive [[hepatopathy]] due to [[heart failure]] or [[Budd-Chiari syndrome]].
*The main microscopic [[histopathological]] findings in portal hypertension are related to [[Cirrhosis (patient information)|cirrhosis]], [[esophageal varices]], [[Hepatic amyloidosis with intrahepatic cholestasis|hepatic amyloidosis]], and congestive [[hepatopathy]] due to [[heart failure]] or [[Budd-Chiari syndrome]].
 
<br>
=== Cirrhosis ===
=== Cirrhosis ===
Robbins definition of microscopic [[histopathological]] findings in cirrhosis includes (all three is needed for diagnosis):<ref>{{cite book | last = Mitchell | first = Richard | title = Pocket companion to Robbins and Cotran pathologic basis of disease | publisher = Elsevier Saunders | location = Philadelphia, PA | year = 2012 | isbn = 978-1416054542 }}</ref>
Robbins definition of microscopic [[histopathological]] findings in cirrhosis includes (all three is needed for diagnosis):<ref>{{cite book | last = Mitchell | first = Richard | title = Pocket companion to Robbins and Cotran pathologic basis of disease | publisher = Elsevier Saunders | location = Philadelphia, PA | year = 2012 | isbn = 978-1416054542 }}</ref>
Line 325: Line 338:
* [[Nodule]] formation
* [[Nodule]] formation
* Disruption of the [[hepatic]] architecture
* Disruption of the [[hepatic]] architecture
 
<br>
=== Esophageal varices ===
=== Esophageal varices ===
The main microscopic [[histopathological]] findings in [[esophageal varices]] are:
The main microscopic [[histopathological]] findings in [[esophageal varices]] are:
Line 331: Line 344:
* [[Blood]] (fresh)
* [[Blood]] (fresh)
* [[Hemosiderin]]-laden [[macrophages]].
* [[Hemosiderin]]-laden [[macrophages]].
 
<br>
=== Hepatic amyloidosis ===
=== Hepatic amyloidosis ===
The main microscopic [[histopathological]] findings in [[Hepatic amyloidosis with intrahepatic cholestasis|hepatic amyloidosis]] is amorphous extracellular pink stuff on H&E staining.
The main microscopic [[histopathological]] findings in [[Hepatic amyloidosis with intrahepatic cholestasis|hepatic amyloidosis]] is amorphous extracellular pink stuff on H&E staining.
 
<br>
=== Congestive hepatopathy ===
=== Congestive hepatopathy ===
The main microscopic [[histopathological]] findings in congestive [[hepatopathy]] (due to [[heart failure]] or [[Budd-Chiari syndrome]]) are:
The main microscopic [[histopathological]] findings in congestive [[hepatopathy]] (due to [[heart failure]] or [[Budd-Chiari syndrome]]) are:

Revision as of 13:47, 27 October 2017

Portal Hypertension Microchapters

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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

Physiology


<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; 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

 
 
 
 
 
 
 
 
 
 
Portal Hypertension
associated conditions
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunological disorders
 
Infections
 
Medication and toxins
 
Genetic disorders
 
Prothrombotic conditions
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Common variable immunodeficiency syndrome[32]
• Connective tissue diseases[33]
• Crohn’s disease[34]
• Solid organ transplant
•• Renal transplantation[35]
•• Liver transplantation[36]
• Hashimoto's thyroiditis[37]
• Autoimmune disease[38]
 
• Bacterial intestinal infections
• Recurrent E.coli infection[39]
• Human immunodeficiency virus (HIV) infection[40]
• Antiretroviral therapy[41]
 
• Thiopurine derivatives
•• Didanosine
•• Azathioprine[42]
•• Cis-thioguanine[43]
• Arsenicals[44]
• Vitamin A[45]
 
• Adams-Olivier syndrome[46]
• Turner syndrome[47]
• Phosphomannose isomerase deficiency[48]
• Familial cases[49]
 
• Inherited thrombophilias [50]
• Myeloproliferative neoplasm[50]
• Antiphospholipid syndrome[50]
• Sickle cell disease[51]
 
 

Gross Pathology

Micronodular cirrhosis - By Amadalvarez (Own work), via Wikimedia Commons[52]
Macronodular cirrhosis[53]
Splenomegaly - By Amadalvarez (Own work), via Wikimedia Commons[54]
Esophageal varices[55]



Cirrhosis

On gross pathology there are two types of cirrhosis:



Splenomegaly

On gross pathology, diffuse enlargement and congestion of the spleen are characteristic findings of splenomegaly.


Esophageal Varices

On gross pathology, prominent, congested, and tortoise veins in the lower parts of esophagus are characteristic findings of esophageal varices.


Microscopic Pathology

Cirrhosis with bridging fibrosis (yellow arrow) and nodule (black arrow) - By Nephron, via Librepathology.org[56]
Hepatic amyloidosis with amorphous amyloids (black arrow) and normal hepatocytes (blue arrow), via Librepathology.org[57]
Congestive hepatopathy with central vein (yellow arrowhead), inflammatory cells, Councilman body (green arrowhead), and hepatocyte with mitotic figure (red arrowhead), via Librepathology.org[58]
Esophageal varices with submucosal vein (black arrow), via Librepathology.org[59]


Cirrhosis

Robbins definition of microscopic histopathological findings in cirrhosis includes (all three is needed for diagnosis):[60]


Esophageal varices

The main microscopic histopathological findings in esophageal varices are:


Hepatic amyloidosis

The main microscopic histopathological findings in hepatic amyloidosis is amorphous extracellular pink stuff on H&E staining.

Congestive hepatopathy

The main microscopic histopathological findings in congestive hepatopathy (due to heart failure or Budd-Chiari syndrome) are:

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.
  52. ↑ <CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)>
  53. ↑ "www.meddean.luc.edu".
  54. ↑ Amadalvarez - Own work, <"https://creativecommons.org/licenses/by-sa/4.0" title="Creative Commons Attribution-Share Alike 4.0">CC BY-SA 4.0, <"https://commons.wikimedia.org/w/index.php?curid=49669333">Link
  55. ↑ <http://wellcomeimages.org/indexplus/obf_images/29/b4/13f38971164f946a97f9d32ddd93.jpg>Gallery: <"http://wellcomeimages.org/indexplus/image/L0074357.html"><"http://creativecommons.org/licenses/by/4.0> CC BY 4.0, <"https://commons.wikimedia.org/w/index.php?curid=36297209">
  56. ↑ "File:Cirrhosis high mag.jpg - Libre Pathology".
  57. ↑ "File:Hepatic amyloidosis - high mag.jpg - Libre Pathology".
  58. ↑ "File:2 CEN NEC 1 680x512px.tif - Libre Pathology".
  59. ↑ "Esophageal varices - Libre Pathology".
  60. ↑ Mitchell, Richard (2012). Pocket companion to Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Elsevier Saunders. ISBN 978-1416054542.

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