Gastrointestinal varices pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Overview

Varices arise from hemodynamic disturbance between the systemic and portal venous system. The majority of venous drainage of the gastrointestinal system occurs via the portal venous system. Whenever there is an interruption of drainage through the portal system (for example due to cirrhosis), the vessels contributing to the porto-caval shunts become more prominent due to increased pressure gradient. The interruption in blood flow leads to the creation collateral vessels that involve veins of the esophagus, stomach, pelvis (hemorrhoids), retroperitoneum, liver, abdominal wall, and other areas.

Pathophysiology

Varices arise from hemodynamic disturbance between the systemic and portal venous system. The majority of venous drainage of the gastrointestinal system occurs via the portal venous system. Whenever there is an interruption of drainage through the portal system (for example due to cirrhosis), the vessels contributing to the porto-caval shunts become more prominent due to increased pressure gradient. The interruption in blood flow leads to the creation collateral vessels that involve veins of the esophagus, stomach, pelvis (hemorrhoids), retroperitoneum, liver, abdominal wall, and other areas.[1][2]

Esophageal varices

Esophageal varices are a major complication of portal hypertension (increased blood pressure in the portal venous system). In order to understand the mechanism leading to the development of esophageal varices, it is important to understand the normal vascular architecture and venous drainage of the esophagus.[3]

Vascular architecture and venous drainage of esophagus

Porto-caval collaterals in esophagus

  • Portal hypertension develops due to the formation of porto-collateral circulation[9]
  • Dilatation and hypertrophy of preexisting vascular channels lead to the formation of these collateral channels[10]
  • Collaterals develop according to the increased portal pressure, and minimum threshold level of hepatic-venous portal gradient may be 10 mmHg for the development of porto-systemic collaterals and esophageal varices[11]

Role of hepatic vasodilators

(a) Nitric Oxide (NO)

(b) Glucagon

(c) Prostacyclin

Role of hepatic vasoconstrictors

(a) Endothelin

(b) Angiotensin II

(c) Norepinephrine

Role of endothelial dysfunction

Mechanism leading to variceal hemorrhage

  • The wall tension of the vessel determines if there will be rupture of the varices[35]
  • The wall tension depends upon the variceal pressure, luminal pressure and radius of the vessel[35]
  • The wall tension is calculated by using the “Laplace's law”:
    • Wall tension = (variceal pressure – luminal pressure) × radius/thickening of variceal wall.
    • The result is the force which is generated by the variceal wall opposing further dilation
  • When the wall tension overcomes the elastic limit of the varices, rupture occurs[36]

Gastric varices

Gastric varices may form secondary to chronic liver disease or splenic vein obstruction; splenic vein obstruction may be caused by pancreatitis, pancreatic pseudocysts, pancreatic carcinoma, other retroperitoneal tumors, or intrinsic thrombosis of the splenic vein

  • Vascular architecture and venous drainage of stomach

Mechanism of development of gastric varices

  • Increased pressure in two main venous pathways are responsible development of gastric varices

(a) Cardiac varices

(b) Fundic varices

Mechanism leading to variceal hemorrhage

  • The wall tension of the vessel determines if there will be rupture of the varices[35]
  • The wall tension depends upon the variceal pressure, luminal pressure and radius of the vessel[35]
  • The wall tension is calculated by using the “Laplace's law”:
    • Wall tension = (variceal pressure – luminal pressure) × radius/thickening of variceal wall.
    • The result is the force which is generated by the variceal wall opposing further dilation
  • When the wall tension over comes the elastic limit of the varices, rupture occurs[36]
  • The vessel wall of the varix is covered by a thinned out serosa and mucosa, and the varix comes to be seen through from the serosa as well as from the mucosa. When such a large varix ruptures, bleeding is profuse and difficult to manage, and the mortality rate is high

Associated Conditions

Genetics

Congenital syndromes leading to gastrointestinal varices may involve genetic mutations in the following genes:[38][39][40]

Pattern of inheritance Disease Locus Gene
Autosomal

recessive

Autosomal recessive polycystic kidney disease (ARPKD) PKHD1 PKHD1
Nephronophthisis 1 NPHP1 2 NPHP1
NPHP2 INVS
NPHP3 NPHP3
NPHP4 NPHP4
NPHP5

(SLSN5)

IQCB1
NPHP6 3

(SLSN6)

CEP290
NPHP7 GLIS2
NPHP8 4 RPGRIP1L
NPHP9 NEK8
NPHP11 TMEM67
NPHP12 TTC21B
NPHP13 WDR19
NPHP14 ZNF423
NPHP15 CEP164
NPHP16 ANKS6
Joubert syndrome and related disorders 5 JBTS1 INPP5E
JBTS2 TMEM216
JBTS3 AHI1
JBTS4 2 NPHP1
JBTS5 3 CEP290
JBTS6 6 TMEM67
JBTS7 4 RPGRIP1L
JBTS8 ARL13B
JBTS9 CC2D2A
JBTS10 OFD1
JBTS11 TTC21B
JBTS12 KIF7
JBTS13 TCTN1
JBTS14 TMEM237
JBTS15 CEP41
JBTS16 TMEM138
JBTS17 C5orf42
JBTS18 TCTN3
JBTS19 ZNF423
JBTS20 TMEM231
TCTN2
Bardet-Biedl syndrome 7 BBS1 BBS1
BBS2 BBS2
BBS3 ARL6
BBS4 BBS4
BBS5 BBS5
BBS6 MKKS
BBS7 BBS7
BBS8 TTC8
BBS9 BBS9
BBS10 BBS10
BBS11 TRIM32
BBS12 BBS12
BBS13 8 MKS1
BBS14 3 CEP290
Meckel syndrome 9 MKS1 8 MKS1
MKS2 TMEM216
MKS3 5 TMEM67
MKS4 3 CEP290
MKS5 4 RPGRIP1L
MKS6 CC2D2A
MKS7 NPHP3
MKS8 TCTN2
MKS9 B9D1
MKS10 B9D2
MKS11 TMEM231
Cranioectodermal dysplasia IFT122
Ellis-van Creveld syndrome EVC 10 EVC
EVC2
Jeune asphyxiating thoracic dystrophy JATD1 Unknown
JATD2 IFT80
Renal-hepatic-pancreatic dysplasia NPHP3
X-linked OFD1 OFD1
Autosomaldominant Autosomal dominant polycystic kidney disease (ADPKD) PKD1 PKD1
PKD2 PKD2

Gross Pathology

On gross examination, the following findings may be observed in gastrointestinal varices:

Microscopic Pathology

On microscopic examination the following findings may be observed:[41][42]

Histological findings in esophageal varices, source:Pathguy.com


References

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