Ministry of Health of the Republic of M oldova [600947]
1
Ministry of Health of the Republic of M oldova
State University of medicine and pharmacy
“N.TESTEMITEANU “
2015
Faculty of General Medicine II
DEPARTMENT OF SURGERY
Medical Thesis
Portal hypertension
Represented by: Usman Bilal VI year Group: 1644
Scientific coordinator:
TUDOR TIMIS
MD.PhD.Associated professor
2
Statement:
I hereby declare that the license thesis titled “Portal Hypertension” is written by me
and has never been submitted to another university or institution of higher
education in the country or abroad. Also that all sources used, including those on
the Internet, are given in the paper with the rules for avoiding plagiarism:
-all the fragments of text reproduced exactly , even in his own translatio n from
another language are written between quotation marks and have a detailed
reference source .
Reformulation of the texts in own words written by other authors have detailed
reference;
Summarizing the idea of the author have detailed reference to the o riginal text.
Date: Usman Bilal
3
LIST OF TABLES
Nr. Table Page
1 Location and blood vessels of collaterals between the
portal and systemic venous circulations. 23
2 Comparison of portal hypertensive gastropathy (PHG)
and gastric antral vascular ectasia (GAVE). 26
3 International ascites club grading system for ascites. 27
4 Revised diagnostic criteria of Hepatorenal syndrome. 29
5 West Haven Criteria of Severity of Hepatic
Encephalopathy 30
6 portal hypertension stages 34
7 General state of patient /classification Child -Pugh 42
8 Surgical shunts 53
9 Specific types of anastomosis 54
4
LIST OF FIGURES
Nr. Figure Page
1 Anatomy of venous system circulation 15
2 Affection with splenic repercussion 17
3 Intrahepatic causes 18
4 Posthepatic obstruction 19
5 Collateral portal circulation 21
6 Gastoesophageal varices localization 22
7 Portal hypertensive enteropathy 26
8 Portal hypertensive enteropathy 26
9 Ascites 28
10 Ascites 28
11 Hepatic hydrothorax X -Ray 32
12 Hepatic hydrothorax X -Ray 32
13 Caput medusa 35
14 Caput medusa 35
15 Hematemesis 36
16 Jaundice ( eye , skin discoloration) 37
17 Jaundice ( eye , skin discoloration) 37
18 Upper endoscopy 39
5
19 Esophageal varices 40
20 Esophageal varices 40
21 mechanism of fluid leakage in Ascites 44
22 Paracentesis 44
23 Paracentesis 45
24 Upper endoscopy 46
25 Banding procedure for varices 47
26 Sclerotherapy of esophageal varices 48
27 Blackmore sengestaken tube 48
28 Transjugular intrahepatic portosystemic shunt 50
29 Portal system presurgical shunting – end-to-side side –
to-side 55
30 Interpositional ”H” partial shunt 55
31 Distal splenorenal shunt , coronary caval shunt 56
32 Patient with liver cirrhosis prepared to a transplant
procedure 57
33 Cirrhotic liver displaced with removal of gall bladder
and anastomosis 58
34 Case 1 – moderate ascites 63
35 Case 1 – swelling of the lower limbs 63
36 Portohepatic stent application 67
6
List of abbreviations
1. (NIAAA) – National institute on alcohol abuse and alcoholism.
2. (NASH) – Nonalcoholic steatohepatitis.
3. (TNF -alpha) – Tumor necrosis factor -alpha.
4. (PH) – Portal hypertension.
5. (GOV) – Gastroesophageal varices.
6. (EV) – Esophageal varices.
7. (IGV) – Isolated gastric varices.
8. (GE) – Gastroesophageal.
9. (HVPG) – Hepatic venous pressure gradient.
10. (ECV) – Ectopic varices.
11. (GI) – Gastrointestinal.
12. (PSC) – Primary scler osing cholangitis.
13. (PHG) – Portal hypertensive gastropathy.
14. (GAVE) – Gastric antral vasculat ectasia .
15. (TIPS) – Transjugular intrahepatic portosystemic shunt.
16. (PHC) – Portal hypertensive colopathy.
17. (SBP) – Spontaneous bacterial peritonitis.
18. (SAAG) – Serum: ascites,albumin gradient.
19. (HRS) – Hepatorenal syndrome.
20. (HE) – Hepatic encephalopathy.
21. (GAB -A) – Gamma Aminobutyric Acid.
22. (HPS) – Hepatopulmonary syndrome.
23. (PPH) – Portopulmonary hypertension.
24. (PAH) – Pulmonary arterial hypertension.
25. (CBC) – Complete Bloo d Count.
26. (LFTs) – Liver function tests.
27. (AST) – Aspartate aminotransferase.
28. (ALT) – Alanine aminotransferase.
29. (FFP) – Fresh frozen plasma.
30. (PTT) – Partial thromboplastin.
31. (INR) – International normalized ratio.
32. (MELD) – Model for End -Stage Liver Disease.
33. (BUN) – Blood urea nitrogen.
34. (ABG) – Arterial blood gases.
35. (DSRS) – Distal spleno -renal shunt.
7
Contents
Part 1 : Theoretical material
1. Introduction ……………………………………………………… 8
2. Objectives of the study ………………………….…………………9
3. Review of literature ………………………………………………10
3.1. Epidemiology …………………………………………………13
3.2. Definition and Anatomy of the liver ………………………..14
3.3 .Anatomy of the portal venous system ………………………15
3.4. Etiology ………………………………………………………16
3.5. Pathogenesis …………………………………………………20
3.6. Clinical presentation ………………………………………..22
3.7. Investigations …………………………………………….…38
3.8. Treatment …………………………………………….………43
Part 2 : Clinical case ……………………………………………………60
Part 3: Conclusion …………………………………………….………69
Part 4 : Bibliography ………………………………………………….70
8
Introduction
As early as the 17th century, it was realized that structural changes in the portal circulation could
cause gastrointestinal bleeding.
In 1902, Gilbert and Carnot introduced the term "portal hypertension" to describe this condition.
Portal hypertension is a pressure in the portal venous system that is at least 5 mm Hg higher than
the pressure in the inferior vena cava. This increased pressure results from a functional
obstruction to blood flow from any point i n the portal system's origin (in the splanchnic bed)
through the hepatic veins (exit into the systemic circulation) or from an increase in blood flow in
the system.
Substantial progress has been made in understanding the pathophysiology of portal hyperten sion.
This knowledge has led to the development of new therapeutic management approaches such as
pharmacological therapies, endoscopic therapies, and Surgical and radiological shunting
procedures .
Although many advances have been made in this field, the c omplications of portal
Hypertension (gastrointestinal hemorrhage, hepatic encephalopathy, hepatorenal syndrome, and
ascites) con tinue to be the cause of significant morbidity and mortality.
Portal hypertension remains one of the most serious sequelae of chronic liver disease.
9
Objectives Of The Study
1. To study clinical and investigative profile of selective patients history of PHT.
2. To study the predictive power of noninvasive investigative parameters (clinical,
biochemical, radiological) for detection of esophageal varices in patients with PHT as
compared to invasive parameter (upper gastrointestinal endoscopy).
3. To discuss the etiopathogenesis of PHT.
4. To study the different modalities of treatment of PHT.
10
Review of Literature
The history of portal hypertension
Philip Sandblom MD PhD University of Lund, Sweden and Lausanne, Switzerland Keywords:
portal hypertension; medical history When studying the history of portal hypertension (PH)l –
one is impressed, as in all branches of medical history, by the inquisitive spirit and the intuition
of early investigators who, with simple technical means, acquired a surprising degree of
knowledge and understanding. Thus, as early as 1543, Vesalius2 drew an an atomical picture of
the portal venous system to which not much has been added. In the 1650s, only 25 years after
Harvey's discovery of the blood circulation, Glisson3 at a dissection in London, established the
portal vein as the vessel by which blood was c ollected from the gastrointestinal tract and
returned to the systemic circulation. His tool was a goose quill which he inserted into the portal
vein and through which, using a pig's bladder, he injected milk .
Vesalius's pictorial of the portal venous system liverward, observing how the liver turned pale as
the milk traversed it on its way to the vena cava and finally to the lungs.
Vesalius had already touched on the core of the pathophysiology by describing a case of
bleeding haemorrhoids and suggested that this was due to a dilatation of the portal branches. The
suspicion that gastrointestinal haemorrhage could be caused by the derangement of the portal
circulation was passed on, two centuries later, by Morgag ni4. He described a patient, observed
by his teacher Valsalva, who had died from gastrointestinal bleeding and was found to have
'polypoid concretions' in the splenic vein and dilatation of the short gastric veins. During the
nineteenth century it became i ncreasingly clear that the clinical picture of splenomegaly, ascites,
and gastrointestinal haemorrhage generally was due to obstruction to the flow in the portal
system. Cases were described by Puckelt5 in 1818 and by Cruveilhier6 in 1832.
In 1841 Racibo rski7 specified that collaterals could develop between the portal and the caval
system via the short gastric veins, haemorrhoidal veins and veins in the abdominal wall. Later
Sappey8 added oesophageal varices as another link. Ore9 commented that the portal vein often
was occluded by a thrombus in patients dying from cirrhosis. Dusausseyl0, who in 1872 wrote an
important thesis 'Studies on oesophageal varices in liver cirrhosis', believed that the obstruction
to portal flow was a consequence of liver cirrhos is. Banti's conception that the syndrome
carrying his name was caused primarily by disease of the spleen'1 was shown to be erroneous by
Warthin12 in 1910 and now the term, Banti's disease, is only of historical interest.
The term portal hypertension, now universally accepted, is a child of this century, introduced by
Gilbert13 in 1902. However, it was not until 1937 that Thompson14 could verify the increase in
portal pressure directly during laparotomy. In 1950 Davidson15, without opening the abdomen,
obtained a 'pressure close to that in the portal vein' by puncturing one of the dilated abdominal
wall veins (the Caput Medusae). Another non -invasive measurement was described in the
following year by Myers16 and by Friedman17, who found that in liver cirrho sis the portal
pressure could be estimated by occlusive catheterization of a hepatic venule. Finally, in 1953,
Lebon18 of Algeria with the knowledge from McNee19 that there is open circulation between
the splenic pulp and the splenic vein, diagnosed PH by percutaneous measurement of the
intrasplenic pressure.
11
At the same time they obtained excellent spleno -portographic images after injection of contrast
material into the spleen.
In 1900, Preble20 had collected 60 cases from the literature of liver cirrho sis where the patient
had died Journal of the Royal Society of Medicine Volume 86 September 1993 545 from
haematemesis. He found that 80% of them had oesophageal varices. It was on these that
therapeutic efforts were first concentrated since haemorrhage fr om these varices is the most
dangerous, and often fatal symptom of PH. Westphal20 was far ahead of his time when, in 1930,
he published his method of temporarily stemming the bleeding by compression of the varices
with a rubber balloon attached to a double lumen gastric tube. However, it was not until 1947
that it was introduced in the USA by Rowntree22.
More lasting results were obtained when Crafoord23 injected sclerosing solution around the
varices via oesophagoscope. Crafoord, a famous pioneer in cardi ac surgery, was also the first to
use heparin for thromboembolism. Like Glisson, Crafoord is an example of how a great spirit
can often make several imprints on developments. The method fell into oblivion for decades but
was later re -established as one of the main therapeutic tools in PH.
It was always felt that local measures were unsatisfactory as the PH persisted, exerting its
injurious effects on the splanchnic organs, causing splenomegaly, ascites, congestive gastritis,
etc. The increasing understandi ng of the chain of events (portal obstruction; PH; splenomegaly;
dilating collaterals; fatal haemorrhage) stimulated a search for a more radical approach aiming at
reduction of the portal pressure. Two roads seemed open: either reducing the bloodflow into the
system or increasing the outflow. Inflow reduction through splenectomy gave only temporary
relief and the attention was therefore directed towards ways of enhancing outflow. The healing
efforts of Nature itself have been strikingly ill -fated in this fi eld. When substituting degenerating
liver parenchyma with the usual fibrous tissue, the portal flow gets strangulated, and when she
looks for a way out, helped by the pressure gradient expanding the collaterals, the dangerous
oesophageal varices are produc ed. The risk of haemorrhage from these vulnerable varices makes
it essential for surgery to find other pathways.
The Dutch surgeon, Talma24, had observed the rich network of small collaterals in peritoneal
adhesions, connecting the portal and the caval s ystems, and suggested increasing them by sewing
the omentum to the abdominal wall. This was first tried by his pupil Lens25 in 1882. The new
collaterals turned out to be entirely inadequate and the method was soon abandoned. In Britain
the operation was kn own by the name of Talma -Morison.
During the last half of the nineteenth century it was commonly believed that animals died
promptly if their portal vein was suddenly occluded. The sturdy medical individualist Nicolai
Eck of Russia was highly skeptical o f the convictions of the day and set about proving that the
dog, at least, could survive sudden and complete portal occlusion provided portal blood flow was
simultaneously diverted into the vena cava26.
In his article, in 1877, Eck27 stated :
I am conducting these experiments with the purpose of clarifying some physiologic problems as
well as to determine whether it would be possible to treat some cases of mechanical ascites by
means of forming such a fistula. I operated on 8 dogs, one recover ed completely and lived in the
12
laboratory for 2,5 months. Because of lack of attention, he ran away. I had to postpone further
experiments because I was called to join the active army.
The Eck fistula was instead thoroughly investigated by a team in Pawl ow's laboratory28. In 1893
they wrote 'As a keen surgeon, Eck claimed that he could release the obstructed flow as the
portal blood could be diverted into the systemic circulation without danger to the organism'. The
Pawlow school showed that this was not entirely true – their most important observation
concerned a derangement of the protein metabolism, resulting in 'meat intoxication',
corresponding to the encephalopathy in liver cirrhosis.
13
Epidemiology
Population -based prevalence data for portal hypertension in the United States are not available,
but portal hypertension is a frequent manifestation of liver cirrhosis. According to the National
Institute on Alcohol Abuse and Alcoholism (NIAAA), liver cirrhosis accounted for almost
30,000 deaths in the United States in 2007, making it the 12th leading cause of US deaths.
The international incidence of portal hypertension is also not known, although it is probably
similar to that of the US, with differences primarily in the causes. In Western countries, alcoholic
and viral cirrhosis are the leading causes of portal hypertension and esophageal varices; 30% of
patients with compensated cirrhosis and 60 -70% of patients with decompensated cirrhosis have
gastroesophageal varices at the time of diagnosis. The frequency of gastroesophageal varices
directly correlates with the severity of the liver disease from 40% in Child class A to 85% in
Child class C.
The de novo rate of development of esophageal varices in US patients with chr onic liver disease
is approximately 8% per year for the first 2 years and 30% by the sixth year. The risk of bleeding
from esophageal varices is 30% in the first year after identification. Bleeding from esophageal
varices accounts for approximately 10% of episodes of upper gastrointestinal bleeding.
Hepatitis B is endemic in the Far East and Southeast Asia, particularly, as well as in South
America, North Africa, Egypt, and other countries in the Middle East. Schistosomiasis is an
important cause of portal hypertension in Egypt, Sudan, southern and sub -Saharan Africa,
Southeast Asia, Caribbean, an d South America. Nonalcoholic steatohepatitis (NASH) is
becoming a major cause of liver cirrhosis in the United States as hepatitis C is becoming a major
cause of liver cirrho sis worldwide [98].
Sex- and age -related demographics
Liver disease demonstrates a sex predilection, with males making up more than 60% of patients
with chronic liver disease and cirrhosis.
In general, alcoholic liver disease and viral hepatitis are the most common causes for esophageal
varices in both sexes. However, veno -occlusive diseases and primary biliary cirrhosis are more
common in females; and in females with esophageal varices, alcoholic liver disease, viral
hepatitis, veno -occlusive disease , and primary biliary cirrhosis are usually responsible. In males
with esophageal varices, alcoholic liver disease and viral hepatitis are usually the cause.
Portal vein thrombosis and secondary biliary cirrhosis are the most common causes of
esophageal va rices in children. Cirrhosis is the most common cause of esophageal varices in
adults.
14
What is Portal Hypertension ?
Portal hypertension is a term used to describe elevated pressures in the portal venous system
(a majo r vein that leads to the liver)
Portal hypertension may be caused by intrinsic liver disease, obstruction, or structural changes
that result in increased portal venous flow or increased hepatic resistance.
Normally, vascular Channels are smooth, but liver cirrhosis can cause them to b ecome irregular
and tortuous with accompanyin g increased resistance to flow [98].
This resistance causes increased pressure, resulting in varices or dilations of the veins and
tributaries. Pressure within the portal system is dependent upon both input from blood flow in the
Portal vein, and hepatic resistance to outflow.
Normally, portal vein pressure ranges between 1 –4 mm Hg higher than the hepatic v ein free
pressure, and not more than 6 mm Hg higher than right atrial pressure.
Pressures that exceed thes e limits define portal hypertension [98].
Anatomy of the liver
The liver is located in the right upper quadrant, from the fifth intercostal space in the
midclavicular line down to the right costal margin [99].
The liver weighs approximately1800 g in men and 1400 g in women. The surfaces of the liver
are smooth and convex in the superior, anterior, and right lateral regions.
Indentations from the colon, right kidney, duodenum, and stomach are apparent on the posterior
surface.
The line between the vena ca va and gallbladder divides the liver into right and left lobes. Each
lobe has an independent vascular and duct supply.
The liver is further divided into eight segments, each containing a pedicle of portal vessels,
ducts, and hepatic veins.
The portal venou s system extends from the intestinal capillaries to the hepa tic sinusoids [99]
[100].
This venous system carries the blood from the abdominal gastrointestinal tract, the pancreas,
gallbladder, and spleen back to the heart (coursing through the liver). The largest vessel in this
system is the portal vein, which is formed by the union of the splenic vein and superior
mesenteric veins. The left gastric and right gastric veins and the posterior superior
pancreaticoduodenal vein drain directly into the portal ve in. The portal vein runs posterior to the
pancreas, and its extrahepatic length may be anywhere from 5 –9 cm. At the porta hepatis, it
Divides into the right and left portal veins within the liver, and the cystic vein typically drain s
into the right hepatic branch [100].
15
Anatomy of the portal venous system:
The portal vein supplies 70% of the blood flow to the liver, but only 40% of the liver oxygen
supply [100].
The remainder of the blood comes from the hepatic artery, and blood from both of these vessels
mixes in the sinusoids.
The liver receives a tremendous volume of blood, on the order of 1.5 liters per minute. The dual
blood supply allows the liver to remain relatively resistant to hypoxemia. Unlike the systemic
vasculature, the hepatic vascular system is less influenced by vasodilation and vasoconstriction.
This is because the sinusoidal pressures remain relatively constant despite changes in blood flow.
A classic example is hepatic vein occlusion resulting in high sinusoidal pressure an d
extracellular extravasation of fluid [101].
To maintain a constant inflow of blood to the liver, hepatic artery blood flow is inversely related
to portal vein flow. This appears to be hormonally mediated rather than neurally mediated, since
it persists i n the transplanted liver.
Figure 1 : anatomy of venous system
https://gi.jhsps.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Cat_ID=BB532D8A -43CB -416C -9FD2 -A07AC6426961&GDL_Disease_ID=E19DBE4A -EE02 -4BDE -9FF9 -A8371834DE4A
16
Etiology
Overview :
Normal portal vein pressures range from 5 –10 mm Hg. The term portal hypertension refers to
elevated pressures in the portal venous system.
Venous pressure more than 5 mm Hg greater than the inferior vena cava pressure is defined as
portal hypertension.
Clinically it may be difficult to detect portal hypertension until pres sures are much higher.
There are many causes of portal hypertension including etiologies above the liver, within the
liver, and below the liver [100][101].
Etiology and pathogenesis :
Portal hypertension appear as one syndrome determined by obstruction of portal
circulation.
obstruction and elevated capillary resistance can be localized anywhere on portal venous
axis – prehepatic, intrahepatic and posthepatic
Classification:
Prehepatic Causes
1. Afections of venous axis :
atresia
angiomatosis
thrombosis
flebitis
2. Afections of regional organs :
biliary afections
pancreatitis
pancreatic cyst and pseudocyst
tumours
adenopathia
abcesses
17
3. Afections with splenic repercusions :
syndrome Banty
primitive splenomegalia
hemopathia
Figure 2 : Afections with splenic repercusions
http://newdesktopwallpapers.info/tag/Portal%20Vein%20Hypertension
Intrahepatic Causes :
1.Diffuse :
hepatic cirrhosis
hepatic fibrosis
hepatic degeneration
intrahepatic venous obstruction
2. Segementar :
hepatic tumours
hepatic cysts
hepatic abscesses
18
Figure 3: intrahepatic causes
http://lookfordiagnosis.com/mesh_info.php?term=hypertension%2C+portal&lang=1
Posthepatic obstructions
syndrome Budd -Chiary (obstruction of hepatic veins)
constrictive pericarditis
global cardiac failure
tricuspid insufficiency
19
Figure 4: posthepatic obstruction
http://lookfordiagnosis.com/mesh_info.php?term=hypertension%2C+portal&lang=1
Portal hypertension is considered an advanced complication of cirrhosis. Once it has developed,
the term "decompensat ed cirrhosis" is used.
Mixt obstruction:
Thrombosis of portal vein at patient with hepatic cirrhosis.
Cytokines
The mechanism of portal hypertension has been the subject of extensive research.
The pathophysiology is thought to involve vasodilators produced by the body.
Namely, cytokines such as tumor necrosis factor -alpha (TNF -alpha) and others may play a role
in stimulating endothelial vasodilators such as nitric oxide and Prostacyclin as well as non –
endothelial vasodilators like glucagon. These molecules may affect pressure and flow in the
splanchnic vasculature, leading to hypertension.
20
Pathogenesis
The pathog henetic factors include:
1. Hepatic fibrosis with compression of portal venules .
2. Compression of venules by regenerative nodules .
3. Increased arterial blood flow .
4. Fatty infiltration and acute inflammation, and in trahepatic vascular obstruction.
5. The hepatic diseases associated with portal hypertension include:
Nutritional cirrhosis, postnecrotic cirrhosis, schistosomiasis, biliary cirrhosis, hemochromatosis,
Wilson's disease ( hepatolenticular degeneration ), congenital hepatic fib rosis, and infil trative
lesions [101][102].
Physiopathology :
Important moments of development of portal hypertension:
● Portal hypertension result from existent disorder in regulation of portal blood aflux and
intrahepatic portal resistance .
● abnormal intrahepatic resistance is loca lized at the level of sinusoids.
● Intrahepatic resistance varied under the influence of physiol ogic and pharmacologic stimulus.
in course of portal hypertension blood flow to portal area is elevated;
● in normal condit ions the value of portal pressure constitute 5 -10 mm col.Hg; portal
hypertension is considered when the pressure are more than 14 mm col.Hg (200 mm H 2O) or the
porto -caval pressure gradient is more 3 mm col.Hg;
● approximately 2/3 of patients with portal hypertension develop: splenomegaly with
hypersplenism, Porto -systemic encephalopathy, portal congestive gastro -, entero -, colopatia or
ascites .
● in hepatic cirrhosis the mechanism of ascites include : portal hypertension ∙ hypoalbuminemia ∙
elevated lymphatic circulation , distribution of renal blood flow, hormonal factor , retention of
water and sodium.
The ways of derivation of portal venous flow depend from localization of obstruc tion on the
spleno -portal axis. Collateral circulation from portal system to systemic venous circulation can
be visceral (II) and/or parietal (IA,B; III; IV), superficial (pure portal type, sup erior and inferior
porto -caval ) and profound (presence of esoph ageal varices and hemorrhoids)[101][102].
21
Figure 5: collateral portal circulation
source of the figure is usmf word materials
• Group IA – porto -gastro -esophageal anastomosis /v.gastrica sinistra, vv.gastrici brevis,
v.esofagealis, v.azygos, v.diaf ragmatica inferior/ – gastroesoph ageal varices – upper
gastrointestinal bleeding (lethality 50 -70% of cases);
• Group IB – rectal porto -caval anastomosis /v.hemoroidalis su perior, vv.hemoroidalis media
inferior / – secondary hemorrhoids with rectorrhagia;
• Group II – periombilical anastomosis /v.periombilicalis parietalis, vv.paraombilicalis/ – “head
of medusa”, syndrome Cruveilhier -Baumgarten;
• Group III – parieto -peritoneal anastomoses /vv.hepato -diafragmalis Sappey, vv.spleno -renalis,
vv.spleno -omentali s, vv.lombaris Retzius/;
• Group IV – splenorenal anastomosis /v.renalis sinistra, v.splenica, vv.diafragmatica,
vv.pancreatica, vv.suprarenalis/.
Cytokines
The mechanism of portal hypertension has been the subject of extensive research.
The pathophysiology is thought to involve vasodilators produced by the body.
Namely, cytokines such as tumor necrosis factor -alpha (TNF -alpha) and others may play a role
in stimulating endothelial vasodilators such as nitric oxide and Prostacyclin as well as n on-
endothelial vasodilators like glucagon. These molecules may affect pressure and flow in the
splanchnic vasculature, leading to hypertension.
22
Clinical presentation
Consequences of portal hypertension are caused by blood being forced down alternate channels
by the increased resistance to flow through the systemic venous system rather than the portal
system. They include
1. Gastrointestinal manifestation:
1.1 esophageal varices:
Approximately 5 –15% of cirrhotics per year develop varices, and it is estimated that the
majority of patients with cirrhosis will develop GE varices over their lifetime. The
presence of GE varices correlates with the severity of liver disease; while only 40% of
child A patients have varices, they are present in 85% of child C patients (Table 2)
[2].Collaterals usually exist between the portal venous system and the systemic veins. The
resistance in the portal vessels is normally lower than in the collateral circulation, and so blood
flows from the systemic bed into the portal bed. However, when PH dev elops, the portal pressure
is higher than systemic venous pressure, and this leads to reversal of flow in these collaterals. In
addition, the collateral circulatory bed also develops through angiogenesis and the development
of new blood vessels in an attem pt to decompress the portal circulation [ 3].
Table 1 : Location and blood vessels of collaterals between the portal and systemic venous
circulations.
Location Postal circulation Systemic circulation
Gastroesophageal
junction Short gastric and left gastric
(coronary) veins Azygos vein
Rectum Superior hemorrhoidal veins Middle and inferior hemorrhoidal
veins
Umbilical (caput
medusa) Left portal via a recannulated
umbilical vein Epigastric venous plexus of the
abdominal wall
Retroperitoneum Mesentric veins Intercostal, phrenic, lumbar, and
renal veins
Unfortunately these collaterals are insufficient to decompress the PH, leading to complications
including variceal bleeding.
23
Figure 6: gastroesophageal varices localization
http://www.nature.com/ajg/journal/v97/n4/full/ajg2002242a.html
http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf
GE area is the main site of formation of varices [4]. Esophageal varices (EV) form when the
HVPG exceeds 10 mm Hg [ 5]. In the lower 2 to 3 cm of the esophagus, the varices in the
submucosa are very superficial and thus have thinner wall. In addition, these varices do not
communicate with the periesophageal veins and therefore cannot easily be decompressed. These
are the reasons why EV bleeds only at this site.
Over the last decade, most practice guidelines recommend to screen known cirrhotics with
endoscopy to look for GE varices. Varices should be suspected in all patients with stigmata of
chronic liver disease such as spider nevi, jaundice, palmar erythema, spl enomegaly, ascites,
encephalopathy, and caput medusa . EV are graded as small (<5 mm) and large (>5 mm), where
5 mm is roughly the size of an open biopsy forceps [ 6].
The rate of progression of small EV to large is 8% per year [ 2]. Decomp ensated cirrhosis ,
presence of red wale marks (defined as longitudinal dilated venules resembling whip marks on
the variceal surface), and alcoholic cirrhosis at the time of baseline endoscopy are the main
factors associated with the progression from small to large EV [ 2]. EV bleeding occurs at a
yearly rate of 5% –15% [7]. The predictors of first bleeding include the size of varices, severity of
cirrhosis, variceal pressure (>12 mm Hg), and the endoscopic presence of red wale marks [ 7, 8].
Although EV bleeding stops spontaneously in up to 40% of patients, and despite improvements
in therapy ov er the last decade, the 6 weeks mortality rate is still ≥20% [ 9].
Gastroesophageal varices (GOV) are an extension of EV and are categorized based on Sarin’s
classification into 2 type s (Figure 1). The most common are Type 1 (GOV1) varices, which
extend along the lesser curvature. Type 2 GOV (GOV2) are those that extend along the fundus.
24
They are longer an d more tortuous than GOV1. Isolated gastric varices (IGV) occur in the
absence of EV and are also classified into 2 types. Type 1 (IGV1) are located in the fundus and
tend to be tortuous and complex, and type 2 (IVG2) are located in the body, antrum, or ar ound
the pylorus. When IGV1 is present, one must exclude splenic vein thrombosis. GV are less
common than EV and are present in 5% –30% of patients with PH with a reported incidence of
bleeding of about 25% in 2 years, with a higher bleeding incidence for f undal varices [ 10].
Predictors of GV bleeding include the size of fundal varices (large (>10 mm) > medium (5 –
10 mm) > small (<5 mm)), severity of cirrhosis (child class C>B>A), and e ndoscopic presence of
variceal red spots (defined as localized reddish mucosal area or spots on the mucosal surface of a
varix) [ 11].
1.2 Ectopic Varices (EcV)
EcV are best defined as large portosystemic venous collaterals occurring anywhere in the
abdomen except for the GE region [ 12]. They are an unusual cause of GI bleeding, but account
for up to 5% of all variceal bleeding [ 13]. Compared to GE varices, EcV are difficult to locate,
occur at distal sites, and when identified, the choice of therapy is unclear, therefore representing
a clinical challenge [ 12]. Furthermore, bleeding EcV may be associated with poor prognosis,
with one study quoting mortality reaching 40% [ 14]. Different areas of EcV are the duodenum,
jejunum, ileum, colon, rectum, peristomal, biliary tree, gallbladder, peritoneum, umbilicus, bare
area of the liver, ovary, vagina, and testis [ 15, 16].
The prevalence of EcV varies in the literature and seems to be related to the etiology of the PH
and the diagnostic modal ities used [ 17]. In patients with PH due to cirrhosis, duodenal varices
are seen in 40% of patients undergoing angiography [ 18]. Results of a survey for EcV conducted
over 5 years in Japan identified 57 cases of duodenal varices; they were located in the duodenal
bulb in 3.5%, the descending part in 82.5%, and the transverse part in 14.0% [ 15].
In contrast to duodenal varices, it appears that most cases of varices in other portions of the small
bowel and colonic varices are seen in patients with cirrhosis who have previously undergone
abdom inal surgery [ 12]. Using advanced endoscopic technologies, particularly capsule
endoscopy and enteroscopy, the prevalence of small bowel varices is estimated to be
approximately 69% in patients with PH [ 19]. The prevalence of colonic varices and rectal varices
has been found to be 34% to 46% [ 20, 21] and 10% to 40% [ 22], respectively, in patients with
cirrhosis undergoing colonoscopy. It is impo rtant to differentiate rectal varices from
hemorrhoids; rectal varices extend more than 4 cm above the anal verge, are dark blue in color,
collapse with digital pressure, and do not prolapse into the proctoscope on examination, whereas
hemorrhoids do not e xtend proximal to the dentate line, are purple in color, do not collapse with
digital pressure, and often prolapse into the proctoscope [ 22, 23]. Stomal varices are a
particularly common cause of EcV and can occur in patients with cirrhosis secondary to primary
sclerosing cholangitis (PSC) [ 12].
25
In the west, because the prevalence of noncirrhotic PH is low, most bleeding EcV is usually
associated with cirrhotic PH (6,8). Although EcV can occur at several sites, bleeding E cV are
most commonly found in the duodenum and at sites of previous bowel surgery including stomas.
In a review of 169 cases of bleeding EcV, 17% occurred in the duodenum, 17% in the jejunum or
ileum, 14% in the colon, 8% in the rectum, and 9% in the perit oneum. In the review, 26% bled
from stomal varices and a few from infrequent sites such as the ovary and vagina [ 24].
Portal biliopathy, which includes abnormalities (stricture and d ilatation) of both extra and
intrahepatic bile ducts and varices of the gallbladder, is associated with PH, particularly
extrahepatic portal vein obstruction [ 25, 26]. They are also seen associated with cirrhosis, non –
cirrhotic portal fibrosis, and congenital hepatic fibrosis [ 27]. While a majority of these patients
are asymptomatic, some present with a raised alkaline phosphatase level, abdominal pain, fever,
and cholangitis. Choledocholithiasis may develop as a complication and manifest as obstructive
jaundice with or without cholangitis [26]. On cholangiography, bile -duct varices may be
visualized as multiple, smooth, mural -filling defects with narrowing and irregularity resulting
from compression of the portal vein and collateral vessels. They may mimic PSC or
cholangiocarcinoma (pseudocholangiocarcinoma sign) [ 28].
1.3 Portal Hypertensive Intestinal Vasculopathies
Mucosal changes in the stomach in patients with PH include portal hypertensive gastropathy
(PHG) and gastric vascular ectasia. PHG describes the endoscopicappearance of gastric mucosa
with a characteristic mosaic, or snake -skin-like appearance with or without red spots. It is a
common f inding in patients with PH [ 29]. The prevalence of PHG parallels the severity of PH
and it is considered mild when only a mosaic -like pattern is present and severe when
superimposed discrete red spots are also seen. Bleeding (acute or chronic) from these lesions is
relatively uncommon, and rarely severe [ 30]. Patients with chronic bleeding usually present with
chroniciron deficiency anemia.
In gastric vascular ectasia, collection of ectatic vessels can be seen on endoscopy as red spots
without a mosaic -like pattern [ 31]. When the aggregate s are confined to the antrum of the
stomach, the term gastric antral vascular ectasia (GAVE) is used, and if aggregates in the antrum
are linear, the term watermelon stomach is used to describe the lesion. The prevalence of GAVE
syndrome in cirrhosis is lo w [32] and can be endoscopically difficult to differentiate from severe
PHG. Therefore, gastric biopsy may be required to differentiate them as histologically GAVE
lesions are com pletely distinct from PHG [33].
26
Table 2: Comparison of portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia
(GAVE).
FEATURE PHG GAVE
Relation with PH Causal Coincidental
Distribution in stomach Mainly proximal Mainly distal
Mosaic pattern Present Absent
Red color signs Present Present
Pathology
Thrombi − +++
Spindle cell proliferation + ++
Fibrohyalinosis − +++
Treatment β-adrenergic blockers
TIPS/shunt surgery Endoscopic
Antrectomy and Billroth I
Liver transplantation
PH: portal hypertension, TIPS: transjugular intrahepatic portosystemic shunt.
Small bowel might also show mucosal changes related to PH, which is called portal hypertensive
enteropathy (PHE). The diagnosis of PHE has been limited in the past due to the difficult access
to the small bowel. With advanced endoscopic techniques such as capsule endoscopy and
enteroscopy, PHE is now thought to be a frequent finding in patients with cirrhosis, perhaps as
common as PHG, and may cause occult GI blood loss [ 34, 35]. Portal hypertensive colopathy
(PHC) refers to mucosal edema, erythema, granularity, friability, and vascular lesions of the
colon in PH. PHC may be confused with colitis [ 36, 37]. Although they are found in up to 70%
of patients with PH and are more common in patients with EV and PHG, they rarely cause
bleeding [ 38, 39].
Figure 7: PHE Figure 8: PHE
https://www.google.md/search?biw=1366&bih=667&tbm=isch&sa=1& q=esophageal+varices&oq=esophageal+varices&gs_l=img.3…24190.28575.0.28665.0.0.0.0.0.0.0.0..0.0.msedr…0…1c.1.64.img..0.0 .0.vZ –
4yuyRsCA#imgrc=nRrm8jQ4KS5n_M%253A%3BPrNE8gOxsMDIMM%3Bhttp%253A%252F%252Fwww.netikka.net%252Fhans.bjorknas%252Fyn0063.jpg%3Bh ttp%253A%252F%252Fimage.frompo.com%252Fd3c105df33c8f
5df2c3be36eaaaaff05%3B500%3B500
27
1.4 Ascites and Spontaneous Bacterial Peritonitis (SBP)
Ascites is defined as the accumulation of free fluid in the peritoneal cavity. Cirrhotic PH is the
most common cause of ascites, which accounts for approximately 75% patients with ascites.
About 60% of patients with cirrhosis develop ascites during 10 years of observation [ 40]. The
developmen t of ascites is an important event in cirrhosis as the mortality is approximately 50%
at 2 years without a liver transplantation [ 41]. The formation of ascites in cirrhosis is due to a
combination of abnormalities in both renal function and portal and splanchnic circulation. The
main pathogenic factor is sodium retention [ 42].
The main clinical symptom of patien ts with ascites is an increase in abdominal girth, often
accompanied by lower -limb edema. In some cases, the accumulation of fluid is so severe that
respiratory function and physical activity is impaired. In most cases, ascites develop insidiously
over the course of several weeks. Patients must have approximately 1500 mL of fluid for ascites
to be detected reliably by physical examination. Dyspnea in these patients can occur as a
consequence of increasing abdominal distension and/or accompanying pleural eff usions.
Increased intra -abdominal pressure might favour the development of abdominal hernias (mainly
umbilical) in patients with cirrhosis and longstanding ascites [ 43].
The current classification of ascites, as defined by the International Ascites Club, di vides patients
in three groups [44]. Patients with refractory ascites are those that do not respond to sodi um
restriction and high doses of diuretics or develop diuretic -induced side effects that preclude their
use.
Table 3: International ascites club grading system for ascites.
Grade of ascites Definition
Grade 1 ascites Mild ascites only detectable by ultrasound
Grade 2 ascites Moderate ascites evident by moderate
symmetrical distension of abdomen
Grade 3 ascites Large or gross ascites with marked abdominal distension
Ascites may not be clinically detectable when present in small volumes. In larger volumes, the
classic findings of ascites are adistended abdomen with a fluid thrill or shifting dullness. Ascites
must be differentiated from abdominal distension due to other causes such as obesity, pregnancy,
gaseous distension of bowel, bladder d istension, cysts, and tumours. Ultrasonography is used to
confirm the presence of minimal ascites and guide diagnostic paracentesis.
Successful treatment depends on an accurate diagnosis of the cause of ascites. Paracentesis with
analysis of ascitic fluid is the most rapid and cost -effective method of diagnosis. It should be
done in patients with ascites of recent onset, cirrhotic patients with ascites admitted to hospital,
or those with clinical deterioration. The most important analyses are cell count, fl uid culture, and
calculation of the serum: ascites albumin gradient (SAAG), which reflects differences in oncotic
pressures and correlates with portal venous pressure. It SAAG is greater or equal to 1.1 g/dL (or
11 g/L), ascites is ascribed to PH with appr oximately 97% accuracy [ 45].
Patients with cirrhosis and ascites are also at risk of developing infections, particularly
spontaneous bacterial peritonitis (SBP). SBP occurs in approximately 10% of hospitalized
cirrhotic patients [ 46], with an associated mortality of 20 –40% if untreated [ 47]. Many patients
are asymptomatic, but clinical signs can include abdominal pain, fever, and diarrhea. The
diagnosis of SBP is based on neutrophil count >250 cells/mm3 in the ascitic fluid.
28
Figure 9 Figure 1 0
http:// en.wikipedia.org/wiki/Ascites
2. Renal Manifestations
2.1. Hepatorenal Syndrome
Hepatorenal syndrome (HRS) is a common complication seen in patients with advanced cirrhosis
and PH [ 48]. HRS can also be seen in other types of severe chronic liver disease, alcoholic
hepatitis, or in acute liver failure . This syndrome generally predicts poor prognosis [ 48]. HRS
has been defined in the literature as a reversible functional renal impairment in the absence of
other causes of renal fai lure, tubular dysfunction, proteinuria, or morphological alterations in
histological studies. Precise and accurate diagnostic criteria have been established in order t o
clearly define this syndrome [49]. The diagnosis remains one of exclusion.
29
Table 4: Revised diagnostic criteria of Hepatorenal syndrome.
(I) Chronic or acute liver disease with advanced liver failure and portal hypertension
(II) Plasma creatinine concentration > 1.5 mg/dL (133 micromol/L)
(III) The absence of other apparent cause: shock, ongoing bacterial infection, volume
depletion, current or recent use of nephrotoxic drugs
(IV) Lack of improvement in renal function after volume expansion w ith intravenous
albumin (1 g/kg of body weight per day up to 100 g/day) for at least two days and withdrawal
of diuretics
(V) Absence of parenchymal kidney disease as indicated by proteinuria >500 mg/day,
microhematuria (>50 red blood cells per high pow er field) or ultrasonographic evidence of
obstructive uropathy or renal parenchymal disease
The reported incidence of HRS is approximately 10% among hospitalized patients with cirrhosis
and ascites. The probability of occurrence of HRS in patients with cirrhosis is around 20% after
1 year and 40% after 5 years [ 50]. The pathogenesis of HRS is not completely understood, but is
likely the result of an extreme underfilling of the peripheral arterial circulation secondary to
arterial vasodilatation in the splanchnic circulation [ 51]. In addition, recent data indicates that a
reduction in cardiac output also p lays a significant role [ 52].
HRS -associated renal failure is seen in late stages of cirrhosis and is marked by severe oliguria,
increased sodium and water retention, volume overload , hyperkalemia, and spontaneous
dilutional hyponatremia. There are two main subtypes of HRS described [ 49]. Type 1 HRS is a
rapidly progressive renal failure that is defined by doubl ing of serum creatinine >2.5 mg/dL
(>221 μmoL/L) or a decrease of 50% in creatinine clearance (<20 mL/min) in less than 2 weeks.
This form of HRS is usually precipitated by gastrointestinal bleeds, large volume paracenthesis,
acute alcoholic hepatitis and SBP [ 53]. In addition to renal failure, patients with type 1 HRS
present deterioration in the function of other organs, including the heart, brain, liver, and adrenal
glands. The med ian survival of these patients without treatment is <2 weeks, and almost all of
them die within 10 weeks after onset of HRS. Type 2 HRS is a moderate and stable renal failure
with a serum creatinine of >1.5 mg/dL (>133 μmoL/L) that remains stable over a lo nger period
and is characterized by diuretics resistant ascites [ 49,54].
30
3. Neurological Manifestations
3.1. Hepatic Encephalopathy
Hepatic encephalopathy (HE) is defined as neurologic and psychiatric dysfunction in a patient
with chronic liver disease. The exact mechanism leading to this dysfunction is still poorly
understood, but multiple factors appear to play a role in its genesis. The liver normally
metabolizes ammonia, produced by enteric bacteria [ 56] and enterocytes [ 57, 58]. In a patient
with PH, ammonia bypasses the liver through portosystemic shunt and reaches the astrocytes in
the brain. Within the astrocyte, ammo nia is metabolized into glutamine, which acts as an osmole
to attract water, thus causing cerebral edema. In addition, direct ammonia toxicity triggers
nitrosative and oxidative stress, which lead to astrocyte mitochondrial dysfunction [ 59, 60].
Another important factor is the enhancement of gamma -aminobutyric acid (GABA -A) receptors
through neuroinhibitory ster oids (i.e., allopregnanolone) [ 61] and benzodiazepine.
Benzodiazepine also contributes to astrocyte swelling through a specific receptor [ 62]. Finally,
tryptophane byproducts indole and oxindole [ 63], manganese [ 64], inflammation, hyponatremia
[65], and reduced acetylcholine through acetylcholinesterase activity [ 66] also contribute to
cerebral dysfunction.
The clinical manifestations of HE can be subtle. Minimal hepatic encephalopathy (grade 0)
(Table 7) can present with impaired driving ability [ 67], minimally impaired psychometric tests,
decreased global functioning, and increased risk of falls [ 68]. In overt hepatic encephalopathy,
diurnal sleep pattern changes will often precede neurologic symptoms. To add to the complexity,
HE can be intermittent or persistent.
Table 5: West Haven Criteria of Severity of Hepatic Encephalopathy
Grade 1 Trivial lack of awareness
Euphoria or anxiety
Shortened attention span
Impaired performance of addition
Grade 2 Lethargy or apathy
Minimal disorientation for time and place
Subtle personality change
Inappropriate behavior
Impaired performance of subtraction
Grade 3 Somnolence to semistupor, but responsive to verbal stimuli
Confusion
Gross disorientation
Grade 4 Coma (unresponsive to verbal or noxious stimuli)
The severity of presentation is usually classified using the West Haven criteria . Grade 1 hepatic
encephalopathy represents lack of awareness, anxiety or euphoria, and short attention span.
Change of personality, lethargy, and inappropriate behavior can be seen in grade 2
31
encephalopat hy. More advanced features include disorientation, stupor, confusion (grade 3), and
can even reach coma (grade 4). Focal neurologic symptoms, including hemiplegia, may also be
observed [ 69]. Physical examination may be normal, but typical signs include bradykinesia,
asterixis, hyperactive deep tendon reflexes and even decerebrate posturing [ 55].
4. Pulmonary Manifestations
4.1. Hepatopulmonary Syndrome
Hepatopulmonary syndrome (HPS) is a triad of liver disease, pulmonary vascular ectasia and
impaired oxygenation. HPS is defined in the literature as a widened alveolar -arterial oxygen
difference (A -a gradient) in room air (>15 mm Hg or >20 mm Hg in patients > 64 years of age)
with or without hypoxemia due to intrapulmonary vasodilatation in the presence of hepatic
dysfunction [ 70, 71]. This syndrome occurs mostly in those with PH (with or without cirrhosis)
and indicates poor prognosis and higher mortality. Estimates of the prevalence of HPS among
patients with chronic liver disease range from 4 to 47%, depending upon the diagnostic criteria
and methods used [ 71–73].
HPS results in hypoxemia through pulmonary microvascular vasodilatation and intrapulmonary
arteriovenous shunting resulting in ventilation -perfusion mismatch [ 74], and can occur even with
mild liver disease [ 75]. Clinically, patients with HPS complain of progressive dyspnea on
exertion, at rest, or both. Severe hypoxemia (PaO 2 < 60 mm Hg) is often seen and stron gly
suggests HPS [ 70, 71]. A classical finding in HPS is orthodeoxia defined as a decreased arterial
oxygen tension by more than 4 mm Hg or arterial oxyhemoglobin desaturation by more than 5%
with changing position from supine to standing. It is associated with platypnea defined as
dyspnea worsened by upright position [ 70, 71]. Platypnea -orthodeoxia is caused by the
worsening of diffusion -perfusion matching and increased shunting at the lung bases in the
upright posit ion. There are no hallmark signs on physical exam; however, cyanosis, clubbing,
and cutaneous telangiectasia (spider nevi) are commonly noted. Furthermore, systemic
arterioembolisation may cause stroke, cerebral hemorrhage, or brain abscess, and can presen t
with neurological deficits.
4.2. Portopulmonary Hypertension
Portopulmonary hypertension (PPH), a well -recognized complication of chronic liver disease,
refers to pulmonary arterial hypertension (PAH) associated with PH when no alternative causes
exist. It is defined by the presence of elevated pulmonary arterial pressure (mean pressure
>25 mm Hg at rest and 30 mm Hg on exertion) elevated pulmonary vascular resistance
(>240 dyne s−1 cm−5) in the presence of a pulmonary capillary wedge pressure <15 mm Hg [ 76].
The prevalence of PPH depends on the patient population studies and severity of the liver
disease, 0.7 –2% and 3.5 –16.1% in cirrhotics and patients undergoing liver transplantation,
respectively. The development of PPH is independent of the cause of PH, and it is often seen in
cirrhosis. It is however, also described in those with PH due to nonhepatic pathologies such as
portal venous thrombosis [ 71, 77]. PH seems to be the driving force of PAH. The pathogenesis
of PPH is not completely understood; however, several theories have been offer ed. The most
widely accepted theory is that a humoral vasoactive substances (e.g., serotonin, endothelin -1,
32
interleukin -1, thromboxane B2, and secretin), normally metabolized by the liver, is able to reach
the pulmonary circulation via portosystemic shunts , resulting in PPH [ 71, 78, 79].
Clinically, most patients with PPH present with evidence of both PAH and PH. Typically
manifestations of PH precede those of PAH. The most common presenting symptom is
progressive dyspnea on exertion [ 80] and less frequently fatigue, palpitations, syncope,
hemoptysis, orthopnea, and chest pain. On physical exam, classical features include edema, an
accentuated P2 and a systolic murmur, indicating tricuspid regurgitation [ 71, 77, 80]. In severe
cases, signs and symptom s of right -heart failure can be noted.
4.3. Hepatic Hydrothorax
Hepatic hydrothorax is an uncommon complication of end -stage liver disease. It is defined as a
pleural effusion greater than 500 mL in patients with cirrhosis in absence of primary cardiac,
pulmon ary, or pleural disease [ 81]. The underlying pathogenesis of hepatic hydrothorax is
incompletely understood. Patients with cirrhosis and PH have abnormal extracellular fluid
volume regulation resulting in passage of ascites from the peritoneal space to the pleural cavity
via diaphragmatic defects generally in the tendinous portion of the diaphragm [ 82]. Negativ e
intrathoracic pressure during inspiration pulls the fluid from the intra -abdominal cavity into the
pleural cavity. Hydrothorax develops when the pleural absorptive capacity is surpassed, leading
to accumulation of fluid in the pleural space. Multiple stu dies have shown the passage of fluid
from the intra -abdominal space to the pleural space via 99mTc -human albumin or 99mTc –
sulphur colloid [ 81].
Clinical manifestations of hepatic hyd rothorax include shortness of breath, cough, hypoxemia,
and chest discomfort [ 81]. Ascites may not always be present. Hepatic hydrothorax should
always be suspected in patients with cirrhosis or PH and undiagnosed pleural effusion, regardless
of the presence of ascites. Serious complications include acute tension hydrothorax with
dyspnoea and hypotension [ 83] and spontaneous bacterial empyema [ 84].
Figure 1 1 Figure 1 2
http://www.mypacs.net/mpv4/hss/medcase?page=42
33
5. Other Organs Manifestations
5.1. Cirrhotic Cardiomyopathy
Cirrhotic cardiomyopathy is defined as a chronic cardiac dysfunction in patients with cirrhosis. It
occurs in up to 50% of patients with advanced cirrhosis. It is characterized by impaired
contractile response and/or altered diastolic relaxation in the absence of other cardiac diseases.
The pathophysiology of this condition is complex, and seemingly related to PH and cirrhosis. In
advanced liver disease, splanchnic vasodilatation leads to a resting hyperdynamic state [ 85].
Plasma volume expands, leading to a relative c entral volume decrease [ 86]. In cirrhosis, the
arterial vessel wall thickness and tone decreases, leading to reduced arterial compliance [ 87, 88].
Autonomic dysfunction may also contribute to blunted cardiac response [ 89]. Ultimately, these
factors lead to systolic and diastolic dysfunction.
Symptoms associated with cirrhotic cardiomyopathy include dyspnea with exertion, impaired
exercise capacity, paroxysmal nocturnal dyspnea, peripheral edema, and orthopnea. Less –
frequent presentations include long QT on electrocardiography, arrhythmia, and sudden death
[90].
5.2. Hepatic Osteody strophy
Hepatic osteodystrophy is defined as bone disease (osteomalacia, osteoporosis, and osteopenia)
associated with liver disease. Osteomalacia and osteoporosis are frequently seen in cirrhotic
patients and can predispose to pathologic fractures. The p athophysiology of osteoporosis in liver
disease is relatively complex. The leading hypothesis suggests that it is related to the uncoupling
of osteoblastic and osteoclastic activity. Osteoclastogenic proinflammatory cytokines
(interleukin 1(Il -1) and tumor necrosis factor α (TNFα)) are increased in hepatic fibrosis.
Moreover, TNFα is increased in a rat model of PH [ 91]. Decreased osteoblastic activity has also
been linked with insulin -like growth factor 1 in a rat model (IGF -1). Increasing IGF -1 levels are
associated with liver disease severity [ 92]. Finally, vitamin K mediates the carboxylation of
glutamyl residues on osteocalcin, stimulating osteoclastic activity [ 93].
Patients with osteoporosis are usually asymptomatic. They may present with pain following a
nontraumatic fracture of the axial skeleton or bone deformity, including pronounced cervical
kyphosis. Osteomalacia presentation is similar and includes proximal muscle weakness [ 94].
.
5.3. Hypersplenism
Hypersplenism is a common complication of massive congestive splenomegaly in patients with
cirrhosis and PH. In this condition, splenomegaly is associated with thrombocytopenia,
leucopenia, or anemia or a combination of any the three [ 95, 96]. Severe hypersplenism is
present in about 1/3 of patients with cirrhosis being assessed for liver tran splantation. Most
patients have no symptoms related to hypersplenism, however severe thrombocytopenia may
increase the risk of bleeding, especially after invasive procedures.
34
Classification of hypersplenism:
1. Grade I – thrombocytopenia.
2. Grade II – thromboc ytopenia and leucocytopenia.
3. Grade III – thrombocytopenia, leucocytopenia and anemia.
6. Conclusion
Portal hypertension secondary to cirrhosis has multisystem effects and complications. Once a
patient develops such complications, they are considered to have decompensated disease with the
high morbidity and mortality. The quality of life and survival of patients with cirrhosis can be
improved by the prevention and treatment of these complications.
In dependency of hemodynamic disorders, gravity of clinical picture, severity of hepatic failure,
portal hypertension are divided in some evolutive stages:
Table 6: portal hypertension stages
Compensated
Decompensated Subcompensated Stage 0 Without clinical and pathomorphological hepati c
lesions; splenomegaly, hypersplenism .
Stage I Pathomorphological hepatic lesions; hepatic
functional tests moderate alterated; splenomegaly
with hypersplenism .
Stage II A Alterated hepatic functional tests; splenomegaly
gastroesofageal varic es.
Stage II B Alterated hepatic functional tests; splenomegaly
gastroesofageal varic es with episodes of bleeding .
Stage III Jaundice, asc ytes, severe hemorrhagia, precoma and
hepatic coma, portal encephalopathia
35
Caput medusa:
Also known as palm tree sign , is the appearance of distended and
engorged paraumbilical veins , which are seen radiating from the umbilicus across the
abdomen to join systemic veins .
The umbilical vein carries oxygenated blo od from mother to fetus in uters , and normally
closes within one week of birth, in portal hypertension , the umbilical vein can become re –
canalized.
Figure 1 3
http:// jaundicepictures.com/Pictures -Of-Jaundice.php http:// piximggif.com/caput -medusa
Figure 1 4
http:// jaundicepictures.com/Pictures -Of-Jaundice.php http:// piximggif.com/caput -medusa
36
Hematem esis
Hematemesis or haematemesis is the vomiting of blood . The source is generally the
upper gastrointestinal tract , typically above the suspenso ry muscle of duodenum . Patients can
easily confuse it with hemoptysis (coughing up blood), although the latter is more common.
Hematemesis "is always an important sign".Vomited blood v olumes in excess of 5.5 l itres could
be life -threatening .
Figure 1 5
http://www.thegastrosurgeon.com/hematemesis/
Melena:
Melena refers to the black, "tarry" feces that are associated with upper gastrointestinal bleeding
The black color is caused by the hemoglobin in the blood being altered by digestive ch emicals
and intestinal bacteria .
37
Jaundice:
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over
the sclerae (whites of the eyes), and other mucous membranes caused by high blood bilirubin
levels .
This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellula r
fluid . Concentration of bilirubin in blood plasma is normally below 1.2 mg/dL(<25 µmol /L). A
concentration higher than approx. 3 mg/dL (>50µmol/L) leads to jaundice.
The term jaundice comes from the French word jaune , meaning yellow .
Figure1 6: scleral discoloration Figure 1 7
http:// jaundicepictures.com/Pictures -Of-Jaundice.php http:// piximggif.com/caput -medusa
38
Diagnosis
Overview
Portal hypertension can be diagnosed in several ways. Clinical diagnosis can be made in the
setting of end -stage liver disease and in the presence of ascites and/or varices.
Subclinical portal hypertension is much more difficul t to diagnose, but low platelet levels, a large
portal vein, and splenic enl argement on imaging studies are suggestive .
Direct or indirect measurements of the portal vein may be accomplished using wedged hepatic
vein pressure or splenic p ulp pressure, but these methods are relatively invasive.
1. Imaging Studies
Imaging studies of patients with portal hypertension are helpful to make a diagnosis and t o
define portal venous anatomy.
Dupl ex Doppler ultrasonography is a noninvasive, low -cost me thod of diagnosis that provides
sophisticated information. It is often the initial procedure performed and p rovides specifics
regarding the direction and velocity of portal flow. Findings of increased hepatic echogenicity,
splenomegaly, portal vein dilatio n, thrombotic occlusio n, collaterals, and gallbladder wall
thickening are in dicative of portal hypertension.
MRI (magnetic resonance imaging) and computed tomography (CT) are not particularly useful
in making a diagnosis, but are capable of providi ng some of the same information.
2. Pressure Measurement Studies
Portal pressure measurement is not generally indicated. It is most often performed in setting of
therapeutic or hemodynamic research studies. Clinically it is used to assess the efficacy of
pharmacological agents or shunting procedures.
Most approaches to portal pressure measurement are relatively invasive, with the exception of
Newer endoscopic techniques.
The most commonly used and preferred method for measuring the portal pressure is by
indirectly calculating this pressure after occlusion of the hepatic vein. This is an invasive
procedure, typically performed by interventional radiologists.
3. Endoscopic Diagnosis
Endoscopy is the standard diagnostic approach in patients with acute gastroint estinal hemorrha ge
after initial resuscitation.
In most patients wit h cirrhosis (60 –80%) bleeding is related to esophageal varices. In addition to
making a definitive diagnosis, endoscopic therapy may be indicated for b leeding. Endoscopic
examination may r equire endotracheal intubation in patients who have significant alteration in
mental status as a result of severe hepatic decompensation.
Gastrointestinal endoscopy allows the physician to visualize and biopsy the mucosa of the upper
gastrointestinal tract includ ing the esophagus, stomach, and duodenum. The enteroscope allows
visualization of at least 50% of the small intestine, including most of the jejunum and different
degrees of the ileum.
During endoscopic procedures, a pharyngeal topical anesthetic may be administered to help
prevent gagging. Pain medication and a sedative may also be given prior to the procedure.
39
The patient is placed in the left lateral position .
Figure 1 8: upper endoscopy
http://drbcshah.com/understanding -upper -endoscopy/
The endoscope — a thin, flexible, lighted tube — is passed through the mouth and pharynx, and
into the esophagus.
The endoscope transmits images of the
Esophagus , stomach, and duodenum to a mon itor, visible to the physician.
Air may be introduced into the stomach to expand the folds of tissue and enhance the
examination.
40
Esophageal varices :
Are extremely dilated sub -mucosal veins in the lower third of the esophagus.
They are most often a consequence of portal hypertens ion, commonly due to cirrhosis,
patients with esophageal varices have a stro ng tendency to develop bleeding.
The gold standard method of evaluation of the varices are made through the endoscopy
which visualize the exact position and morphology of this cond ition.
Figure 1 9: different localization of varices Figure 20: esophageal varices
http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf
41
Laboratory Studies
Laboratory studies are directed towards investigating the etiologies of cirrhosis, which is the
most common cause of portal hypertension. The rate and volume of bleeding in the patient
should be assessed .
Gain venous access and obtain blood for immediate hematocrit measurement. Obtain a type and
cross -match for possible blood product transfusion. Measure the platelet count and prothrombin
time (PT), send blood for renal and liver function tests (LFTs), and measure serum electrolyte
levels.
Complete blood count (CBC)
The presence of anemia , leukopeni a, and thrombocytopenia may be present in patients with
cirrhosis. Anemia may be secondary to bleeding, nutritional deficiencies, or bone marrow
suppression secondary to alcoh olism. Pancytopenia can result from hypersplenism, a common
complication in patients with portal hypertension. Serial monitoring of the hemoglobin and
hematocrit value is useful in patients with suspected ongoing gastrointestinal bleeding.
Liver function t ests
Abnormal liver function can be approached as a transaminitis (an elevation of the plasma activity
of aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) or cholestasis (an
elevation of bilirubin, especially conjugated bilirubin, with or without increased alkaline
phosphatase [ALP] activity), both of which may occur in cirrhosis. However, normal LFTs do
not exclude liver disease, as a "burned out" liver (ie, one that loses features of disease activity)
may not give ri se to aminotransfer ase activity.
Type and cross -match
Transfusion with packed red blood cells (RBCs) and fresh frozen plasma (FFP) are usually
required in patients with massive variceal bleeding.
Coagulation tests
Coagulation studies include PT, partial thromboplastin time ( PTT), and international normalized
ratio (INR). Because the synthetic function of the liver is impaired in cirrhotic patients,
coagulopathy with prolonged PT and PTT is expected; INR is also used to assess the severity and
prognosis of the liver disease th rough Model for End -Stage Liver Disease (MELD) score
calculation (see the MELD Score calculator ). See also the Medscape Reference
articles Cirrhosis and Liver Transplantation .
Blood urea nitrogen, creatinine, and electrolytes
Blood urea nitrogen (BUN) and creatinine levels may be elevated in patients with esophageal
bleeding; BUN is also used in calculating the Blatchford bleeding score in the initial evaluation,
and serum creatinine results are used in calculating the MELD score.
Arterial blood g as (ABG) and pH measurements
42
A high anion gap may suggest hyperlactatemia or hyperammonemia.
Hepatic and viral hepatitis serologies
Obtain viral hepatitis serologies, particularly hepatitis B and C. These may help in assessi ng the
cause of liver cirrhosis.
Other laboratory tests may include the following:
Albumin levels – Hypoalbuminemia is commonly found owing to the liver's impaired synthetic
function
Antinuclear antibody, antimitochondrial antibody, antismooth muscle antibody
Iron indices
Alpha1 -antitrypsin deficiency
Ceruloplasmin, 24 -hour urinary copper – Consider this test only in individuals aged 3 -40 years
who have unexplained hepatic, neurologic, or psychiatric disease .
Therapeutic tactics in portal hypertension depend of numerous factors:
Table 7: General state of patient /classification Child -Pugh
Classification Child -Pugh
A or I B or II C or III
Bilirubinemia (mmol/l) <35 35-50 >50
Albuminemia (g/l)
>35 28-35 <28
Protrombinemia (%) >70 40-70 < 40
Ascytes Absent easy to controlled difficult to controlled
Encephalopathia Absent Minimal coma
Surgical risk 10% 31% 76%
every parameter is apreciated by 1 -3 points; sum of these 5 parameters
between 5 -15 permit repartization of patients in 3 groups (classes): group
A or I (rating 5 -6); group B or II (rating 7 -9); group B or III (rating 10 –
15).
43
Treatment
Overview
Treatment of portal hypertension is aimed at prevention of complications. The main goal of
therapy is to decrease portal pressures. This is generally difficult to achieve and adequately
maintain [98].
Indications for surgery in portal hypertension
1. correction of portal hypertension when isn’t severe morpho -functional hepato -lienal
changes, ascites , encephalopathy , serum bilirudinum < 35 mmol/l, serum albuminum >
35 g/l;
2. variceal digestive bleeding which can’t be controlled therapeutically and endoscopically;
3. frequent recidives of variceal digestive bleeding;
4. giant splenomegaly with compression of regional organs and anatomical formati ons;
5. Ascites refractory to medical therapy.
Ascites
Ascites is the presence of excess fluid in the peritoneal cavity. Ascites frequently develops in
patients with chronic liver disease, bu t may be due to a wide range of c auses.
Clinically, patients may be asymptomatic or may have a variety of complaints including early
satiety, increase in abdominal girth, o r respiratory distress (depending upon the amount of fluid
accumulation in the abdomen. Patient with ascites often have abdominal distention, tympanic of
the top, bulging flanks, puddle sign, fluid wave, or shifting dullness on physical examination.
The most important aspect in treating ascites is to restrict sodium to less than 2 g per day.
More restrictive regimens are difficult to accomplish in the ou tpatient setting. Water restriction is
generally not necessary unles s patients develop hyponatremia.
In this setting, fluid restriction to less than 1.5 liters per day is generally adequate. Diuretic
therapy, to reduce sodium retention by the kidneys, is generally required. This is a chieved
through blocking the effects of the salt -regulatory hormone, aldosterone. Loop diuretics function
at the ascending limb of the loop of Henle. Generally, a combination of spironolactone or other
potassium -sparing diuretic along with a loop diuretic is required for complete diuresis.
Patients need to be monitored c losely for side effec ts, which include hyponatremia,
hyperkalemia, hypokalemia, dehydra tion, hypotension, and azotemia.
Mechanism of ascites in portal hypertensio n; S=stomach; C=colon; I=intestine.
Large -volume paracentesis may still be required in patients with difficult -to-control ascites, or in
patients who do not tolerate diuretic therapy. Abdominal paracentesis may be used to
therapeutically remove ascites and is useful in relieving respiratory difficulties, acute oliguria or
pain. Paracentesis is performed at the bedside. After sterilization of the abdominal wall, a local
anesthetic is administered. A sterile needed is inserted by the physician into the abdomen and the
ascetic fluid aspirated .
Infusion of intravenous albumin after large -volume (greater than 5 liters) paracentesis is
preferred.
Ascetic fluid being drained from abdomen to bottle [98].
44
Figure 21: mechanism of leakage in ascites
Mechanism of ascites in portal hypertension; S=stomach; C=colon; I=intestine.
http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/li ver/portal_hypertension.pdf
Large -volume paracentesis may still be required in patients with difficult -to-control ascites, or in
patients who do not tolerate diuretic therapy. Abdominal paracentesis may be used to
therapeutically remove ascites and is use ful in relieving respiratory difficulties, acute oliguria or
pain. Paracentesis is performed at the bedside. After sterilization of the abdominal wall, a local
anesthetic is administered. A sterile need le is inserted by the physician into the abdomen and t he
ascetic fluid aspirated .
Infusion of intravenous albumin after large -volume (greater than 5 liters) paracentesis is
preferred.
Ascitic fluid being drained from abdomen to the medical drainage . [98].
Figure 22: paracentesis
http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf
45
Figure 23: paracentesis
http:// www.escfflorida.com/ESCF_page/paracentesis.htm
Varices
Varices are varicose veins, visible on endoscopy, an upper GI series or other imaging studies,
that occur in the esophagus or sto mach as a result of portal hypertension . Cirrhosis causes severe
scarring of the liver and impedes the normal circulation of blood. Varices develop when portal
blood is rerouted to the systemic circulation, through collateral vessels, because of increased
resistance to blood flow to or through the liver. Obstructions may occur in the hepatic veins,
sinusoids, or portal veins. The pressure within these irregular vessels is great and they have the
potential to rupture .
Acute bleeding from varices or nonvarice al sites in patients with portal hypertension requires
prompt and appropriate measures to control bleeding and prevent recurrent episodes. Therapy is
aimed at the prevention of recurrent episodes of variceal bleeding by lowering portal p ressure
and eliminating varices [99].
46
Medical Therapy
Medical management of bleeding esophageal or gastric varices may be instituted once the cause
of the hemorrhage is documented to be variceal in origin. Drug treatment is aimed at reducing
portal inflow, or collateral or intrahepatic resistance. When the hepatic venous pressure gradient
is below 12 mm Hg, the danger of variceal bleeding is relatively low. Use of beta -blockers has
been shown to decrease portal pressures, but side effects of the drugs are somet imes prohibitive.
Propranolol is a nonselective beta -blocker that has been extensively studied and is effective in
decreasing portal pressures. It decreases the risk of variceal bleeding both as a primary
prophylaxis and after an initial bleeding episode. The dose needs to be titrated to decrease resting
heart rate by 25%. Unfortunately, in patients with cirrhosis and no varices, the side -effects
outweigh the benefits of beta -blockers therefore these medications should not be used for the
prevention of vari ceal development. There are no other medical therapies that can be
recommended to prevent variceal bleeding [100] .
Use of vasopressin in the acutely bleeding patient is effective and works by decreasing
splanchnic blood flow. Vasopressin therapy should be instituted in an intensive care unit through
a central venous access line. The use of this drug is associated with side effects of
vasoconstriction in other vascular beds, including cardiac vessels. Vasopressin should be
administered with sublingual nitrog lycerin. Somatostatin is currently the preferred drug for acute
variceal bleeding. It also acts as a vasoconstrictor, but works only on the splanchnic bed, and
therefore has fewer side effects. It is given as an intravenous bolus at 50 micrograms, followed
by a constant infusion of 50 micrograms per hour.
The short -term (7 days) administration of antibiotics to patients with cirrhosis and acute variceal
hemorrhage is the standard of practice. In these patients, antibiotics have been shown to reduce
the rate of re -bleeding and increase overall survival. Antibiotics should be administered
irrespective of the presence of ascites. It is preferred to select an antibiotic to target gram
negative bacteria [100] .
Endoscopic Therapy
Endoscopy plays a critical role in the diagnosis and treatment of gastrointestinal hemorrhage.
Treatment options include sclerotherapy, banding of esophageal varices and balloon tamponade
to control bleeding.
Figure 24
https://gi.jhsps.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Cat_ID=551CDCA7 -A3C1 -49E5 -B6A0 -C19DE1F94871&GDL_Disease_ID=46159D68 -6ED3 -4F76 -895B -99D8BBBB46EF
47
Banding
Acute variceal hemorrhage is ideally managed by variceal ligation with elastic rings, commonly
called banding .
Figure 25: A, Endoscope with band ligatures on tip; B, banded esophageal
varices; C, corresponding endoscopic image.
http://www.hopkinsmedicine.org/gastro enterology_hepatology/_pdfs/liver/portal_hypertension.pdf
This method is performed endoscopically, and is safe and effective. This technique employs the
use of small elastic rings that are placed over a suctioned varix.
When a patient with suspected acut e variceal hemorrhage is admitted to the hospital, treatment
should be immediately initiated with the aforementioned pharmacologic therapies (somatostatin
analogue). Then, upper endoscopy with variceal ligation should be attempted within twelve
hours. Band ing has fewer side effects and complications than sclerotherapy [100].
Sclerotherapy
The use of sclerotherapy, or injection of a sclerosing agent directly into and around the varices,
has been well studied. The technique consists of injecting 1 –10 mL of sclerosing agent (sodium
morrhuate, sodium tetradecyl sulfate, ethanolamine oleate, or absolute alcohol) into the varix
beginning at the gastroesophageal junction and circumferentially into all columns. There is
considerable variation in the type and volu me of the agent used, as well as the site of injection.
Comparison studies of various techniques and solutions have not shown significant advantages
of any one method. In the setting of acute variceal hemorrhage, sclerotherapy should be reserved
for patients in whom band ligation is not technically feasible. After the initial sclerotherapy
session,
Subsequent sessions are scheduled with the intent to completely obliterate the varices. Common
side effects include tachycardia, chest pain, fever, and ulcer ation at the injection site [100] .
48
Figure 26: Sclerotherapy for esophageal varices.
http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf
Balloon Tamponade
Balloon tamponade is useful to control variceal
bleeding through compression. Use of one of
three commercially available balloons to
tamponade bleeding esophageal or gastric
varices can be employed when medical
management has not been successful, and
endoscopic management has failed or is
unavailable .
Although quite effective as a temporary
measure, there is a high risk of complications ,
especially aspiration. Only experienced
physicians should perform the tube placement,
and the patient should be carefully and
continuously monitored . [100] .
Figure 27: blakemore sengstaken tube
http://www.forumenfermagem.org/comunicacao/reportagens/item/3510 -encontro -de-enfermagem -na-urgencia -a-vida-por-um-fio
49
Portal hypertensive gastropathy
Refers to changes in the mucosa of the stomach in patients with portal hypertension; by far the
most common cause of this is cirrhosis of the liver. These changes in the mucosa include
friability of the mucosa and the presence of ectatic blood vessels at the surface. Patients with
portal hypertensive gastropathy may experience bleeding from the stoma ch, which may
uncommonly manifest itself in vomiting blood or melena; however, portal hypertension may
cause several other more common sources of upper gastrointestinal bleeding, such as esophageal
varices and gastric varices. On endoscopic evaluation of t he stomach, this condition shows a
characteristic mosaic or "snake -skin" appearance to the mucosa of the stomach [101] .
Treatment
Argon plasma coagulation, seen here to treat gastric antral vascular ectasia , has also been used to
treat bleeding from portal hypertensive gastropathy
Medications
Several treatment options have been developed for portal hypertensive gastropathy. The first is
the use of beta-blockers , which reduce portal pressures. Non -selective beta blockers (such
as propranolol and nadolol ) have been used to decrease the pressure of the portal vein in patients
with esophageal var ices, and have been shown to regress portal hypertensive gastropathy that has
been worsened by medical treatment of varices. Propranolol has also been evaluated in patients
with chro nic cirrhosis and portal hypertensive gastropathy Other medications that primarily treat
bleeding, including anti -fibrinolytic medications such as tranexamic acid have also been used in
case reports of patients with portal hypertensive gastropathy. These medications work by
stabilizing deposits of fibrin at sites that ordinarily would bleed.
Finally, octreotide , an analogue of somatostatin that leads to vasoconstriction of the portal
circulation, can be used for active bleeding due to portal hypertensive gastropathy. Sucralfate , a
coating medication has also been used, but evidence is from animal models [101] .
Procedural
Portal hypertensive gastropathy can also be treated with endoscopic treatment delivered through a fibre –
optic camera into the stomach. Argon plasma coagulation and electrocaute ry have both been used to stop
bleeding from ectatic vessels, and to attempt to obliterate the vessels, but have limited utility if the disease
is diffuse.
Transjugular intrahepatic portosystemic shunt procedures, or TIPS involve decompressing the portal vein
by shunting a portal venule to a lower pressure systemic venule, under guidance with fluoroscopy . Since
it treats the root cause of portal hypertension gastropathy, it has been putatively used for the condition.
The literature reports suggest both regression of portal hypertensive gastropath y on endoscopic images
and improvement in bleeding after TIPS.
Finally, cryotherapy involves the use of pressur ized carbon dioxide administered through the endoscope
to freeze and destroy tissue in a focal area. It is being studied for the treatment of portal hypertensive
gastropathy [101].
50
Control of hepatic encephalopathy
A standard treatment plan may involve lactulose , bowel enemas, and use of oral antibiotics such
as rifaximin, neomycin, metronidazole, vancomycin, and the quinolones. Previously, restriction
of dietary protein was recommended but this is now refuted by a clinical trial which showed no
benefit. Instead, the maintenance of adequate nutrition is now advocated [102] .
Shunting Procedures
Nonsurgical Transjugular Intrahepatic Portal -Systemic Shunt (TIPSS)
Transjugular intrahepatic portal -systemic shunting is a radiologic procedure that has become
very popular as an alternative method of controlling acute bleeding, especially if gastric varices
are pres ent. It is also indicated in patients who have had recurrent bleeding despite medical or
endoscopic management.
Contraindications to TIPSS placement include severe liver dysfunction, renal failure, and heart
failure.
The procedure itself requires a high le vel of expertise, and is performed under fluoroscopic
guidance using intravenous sedation. First, access to the hepatic vein is obtained through the
right internal jugular vein. A needle is passed through the liver parenchyma into the portal vein,
followed by dilation of the tract , and subsequent placement of a metal stent. The stent is then
dilated to achieve a portal to hepatic vein gradient of less than 10 mm Hg [102] .
Figure 28
Transjugular intrahepatic portal systemic shunt; A, B, shunt placement and
balloon inflation.
A’B’, x -ray showing balloon and stent in place; C, expandable mental stent;
C’, x -ray showing expandable metal stent in place.
http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf
51
Success is over 90% in experienced hands. The long -term utility of the stent is limited by a high
occlusion rate from thrombosis or stenosis. The main side effect is worsening hepatic
encephalopathy, which can be severe in a minority of patients. The patency of the stent can be
checked by Doppler ultrasound .
Stenosed stents can generally be revised.
.
What Tests Might Be Performed Before the TIPS and DSRS Procedures?
Before receiving either of these procedures for portal hypertension, the following tests may be
performed to determine the extent and severity of your condition:
Evaluation of your medical history
A physical exam
Blood tests
Angiogram (an X -ray test that takes pictures of the blood flow within a particular artery)
Ultrasound
Endoscopy
Before either the TIPS or DSRS procedure, your doctor may ask you to have other tests, which
may include an electrocardiogram (EKG) (a test that records the electrical activity of your heart),
chest X -ray, or additional blood tests. If your doctor thinks you will need additional blood
products (such as plasma), they will be ordered at this time [103].
What Happens During the TIPS Procedure?
During the TIPS procedure, a radiologist makes a tunnel through the liver with a needle,
connecting the portal vein to one of the hepatic veins (veins connected to the liver). A metal stent
is placed in this tunnel to keep it open.
The procedure reroutes blood flow in the liver and re duces pressure in abnormal veins, not only
in the stomach and esophagus, but also in the bowel and the liver.
This is not surgery. The radiologist performs the procedure within the vessels under X -ray
guidance. The process lasts one to three hours, but you should expect to stay in the hospital
overnight after the procedure [103] .
52
How Successful Is the TIPS Procedure?
The TIPS procedure controls bleeding immediately in more than 90% of patients with portal
hypertension. However, in about 20% of patients, the shunt may narrow, causing varices to re –
bleed at a later time. .[103].
What Complications Are Associated With TIPS?
Shunt narrowing or blockage can occur within the first year after the TIPS procedure. Follow -up
ultrasound exams are performed frequent ly after the TIPS procedure to detect these
complications. The signs of a blockage include increased ascites (accumulation of fluid in the
abdomen) and re -bleeding. This condition can be treated by a radiologist who re -expands the
shunt with a balloon or r epeats the procedure to place a new stent.
Encephalopathy, or abnormal functioning of the brain, can occur with severe liver disease.
Hepatic encephalopathy can become worse when blood flow to the liver is reduced by TIPS,
which may result in toxic substan ces reaching the brain without being metabolized first by the
liver. This condition can be treated with medications, diet, or by making the shunt inaccessible.
.[103].
53
Surgical Shunts
The aim of surgical shunting in portal hypertension is threefold:
1) To reduce portal venous pressure.
2) To maintain hepatic and portal blood flow .
3) To try to reduce or not complicate he patic encephalopathy .
Currently, there is no procedure that reliably and consistently fulfills all of these criteria.
The operative mortality in shunting procedures is about 5% in patients who are good surgical
risks, and about 50% in those who are poor surgical risks. Surgical shunts are often very
effective in patients with mild liver disease but have severe portal hypert ension, such as in the
case of acute hepatic vein occlusion (Budd -Chiari syndrome).
Table 8: Surgical shunts:
Shunts effectiveness complications
Total portal -systemic
Portocaval shunt
Mesocaval shunt
Central spleno -renal shunt Control of variceal bleeding;
side-to-side has advantage
over end -to-side anastomosis
for control of ascites. Can worsen liver function;
encephalopathy; high
incidence of thrombosis in
meocaval and central spleno –
renal; 10% operative
mortality.
Partial portal -systemic
Interp ositional shunt
8mm diameter Good if shunt size remains
constant. Difficult keeping shunt
systemic: constant size .
Selective shunt
Distal spleno -renal shunt
Coronary caval shunt Control of varices, does not
relieve portal hypertension
centrally. 6% oper ative mortality may
worsen encephalopathy.
Portocaval anastomosis
A portacaval anastomosis (also known as Porto -systemic anastomosis or portal caval system) is a
specific type of anastomosis that occurs between the veins of portal circulation and those
of systemic circulation . The inferior end of esophagus and the inferior part of the rectum are
some of the most important sites of portal systemic anastomosis .
In portal hypertension , as in the case of cirrhosis of liver , the anastomoses become congested and
form venous dilatations. Such dilatation can lead to esophageal varices and
rectal hemorrhoids . Caput medusa can also result .
54
Table 9: Specific types of anastomosis
Region Name of
clinical
condition Portal circulation Systemic circulation
Esophageal Esophageal
varices Esophageal branch of left
gastric vein Esophageal branches of Azygos
vein
Rectal Rectal Varices Superior rectal vein Middle rectal veins and inferior
rectal veins
Paraumbilical Caput medusa Paraumbilical veins Superficial epigastric vein
Retroperitoneal (no clinical name) Right colic vein , middle
colic vein , left colic vein Renal vein , suprarenal
vein, paravertebral vein ,
and gonadal vein
Intrahepatic Patent ductus
venosus Left branch of portal vein Inferior vena cava
It can be one of the conditions caused by portal hypertension . A useful mnemonic is that portal
hypertension causes problems in the butt, the gut, and caput. A dilated inferior mesenteric vein
may o r may not be related to portal hypertension.
55
Figure 2 9: A, Portal system, presurgical shunting; B, end -to-side portocaval
shunt; C, side -to-side portocaval shunt; D, mesocaval “C” shunt; E, central
splenorenal shunt.
http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf
Figure 30 :Interpositional “H” shunt (partial shunt).
http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf
56
Figure 3 1: A, Distal splenorenal shunt; B, coronary caval shunt
. http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf
What Happens in the DSRS Procedure?
The DSRS is a surgical procedure during which the vein from the spleen (called the splenic vein)
is detached from the portal vein and attached to the left kidney (renal) vein. This surgery
selectively reduces the pressure in the varice s and controls the bleeding associated with portal
hypertension. It is usually performed only in patients with good liver function.
A general anesthetic is given before the surgery, which lasts about four hours. You should expect
to stay in the hospital f rom seven to 10 days following surgery [103] .
How Successful Is the DSRS Surgery?
The DSRS procedure provides good long -term control of bleeding in many people with portal
hypertension. DSRS controls bleeding in more than 90% of patients, with the highest risk of any
re-bleeding occurring in the first month.
57
What Complications Are Associated With DSRS Surgery?
Ascites, an accumulation of fluid in the abdomen, can occur with DSRS surgery. This can be
treated with diuretics and by restricting sodium in the diet [103] .
Liver Transplantation
Liver transplantation is the only effecti ve treatment for end -stage liver disease. This option offers
excellent patient survival and rehabilitation. Challenges of liver transplantation include a scarcity
of human cadaver donors, rejection, and the limited financial resources of most patients. Liv er
transplantation is a long and complex surgery that involves the removal and the replacement of
the body's largest solid organ. It requires surgical expertise in biliary and vascular reconstruction.
Variceal bleeding alone is not an indication for transplantation; refractory bleeding can elevate
the listing status of patients awaiting transplant .
Figure 32: Patient with liver cirrhosis prepared to a transplant procedure.
http://iahealth.net/liver -transplants -and-alcoholics/
58
Figure 33: cirrhotic liver displaced with gallbladder removal and anastomosis
Lifestyle Changes Should Be Made for Portal Hypertension?
http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf
Maintaining good nutritional habits and keeping a he althy lifestyle may help you avoid portal
hypertension. Some of the things you can do to improve the function of your liver include the
following:
Do not use alcohol or street drugs.
Do not take any over -the-counter or prescription drugs or herbalmedicines without first
consulting your doctor or nurse. (Some medications may make liver disease worse.)
Follow the dietary guidelines given by your health care provider, including eating a low -sodium
(salt) diet. You will probably be required to consume no more t han 2 grams of sodium per day.
Reduced protein intake may be required if confusion is a symptom. A dietitian can create a meal
plan for you.
59
What is the prognosis for portal hypertension?
Portal hypertension is a complication of an underlying liver disease. It is a disease that can be
controlled but requires patients to be compliant with dietary restrictions and to abstain from
alcohol and drugs. Survival rates can be quite high as long as some liver function is maintained.
The worse the liver function, the worse the prognosis .
60
Clinical case
Age:37 yrs
weight: 50kg
Sex: Male
Reasons for Admission :
Vomiting since 5 days (3 -4 episodes per day) and one episode of
hematemesis
Yellowish discoloration of eyes from 10 days
Dark yellow colored urine since 10 days
Swelling of both lower limbs since 10 days
Abdominal distension since 15 days
Feeling so much drowsy and giddiness since 2 days
1. Patient medical history PMHx : nothing significant.
2. Social history:
Known Alcoholic since 16 years.
(Drinks approximately 180ml of whisky per day.)
Known Smoker since 15 years (smokes one packet of Beedies per day) .
Day 1:
BP: 120/80 mmHg Pulse: 80 BPM Weight: 50 kg
• O/E
• Alcohol smell on breath+
• Pedal edema+
• Abdominal distension + (88 cm)
• Icterus+
• Splenomegaly+
• Hepatomegaly+
• Platinychia+
61
The patient is advised for:
• Complete Haemogram
• Blood urea and Serum creatinine
• ECG
• LFT, Upper GI Endoscopy, USG abdomen
• Strict I/O chart and weight monitoring
Provisional Diagnosis
• Alcoholic liver disease
• Portal Hypertension?!
Drug Dose Route Frequency
DNS with MVI 1 pint IV 75 ml/hour
T.thiamine propyl
disulphide 75 mg Po 0-1-0
inj.pantoprazole 40 mg IV 1-0-0
Inj.odansetron 4 mg IV 1-1-1
Tab.propranolol 10 mg Po 1-1-1
Tab. Toresemide +
spironolactone 10 mg +100mg Po 1-1-0
Syp. lactulose 15 ml Po 1-1-1
Tab.Amoxacillin +
Clavulanic acid 625 mg + 500 mg Po 1-0-1
Those medication is received by the patient.
Day 2:
Hematology: Biochemistry :
Hb:8.8 g% RBS:92 mg/dl
WBC:6800 Cells/Cumm Urea:20 mg/dl
DLC: N: 90%(40-75) Secr:0.8 mg/dl
E:02% AST: 170(0-40)
L:08% (20-25) ALT: 83(0-40)
62
M:00% ALP: 203(37-147)
ESR: 35 mm/hr Total Protein: 6.9 mg/dl
PLT: 75000 (1.5-5) Albumin: 3.0(3.4 -4.5)mg/dl
PCV: 32.4% (45+_7) A/G Ratio: 0.8 (1.2-2.5)
MCV: 66fl(77-93)
Bilirubin:T: 5.64(0.1.1)
MCH: 26pg (27-32) D: 3.85(0-0.2)
MCHC: 27 % (31-35) ECG : Within normal limit
Impression :Microcytic anemia with blood loss with relative Neutrophilia and
thrombocytopenia
Stool examination: Occult blood : Positive
• BP: 120/70 mmHg Pulse : 74 BPM Weight: 49 kg
• No fresh complaints. V omiting subsided
• Icterus+
• Platinychia+
• Hepatosplenomegaly +
USG Abdomen :
Cirrhosis of liver, Mild to moderate ascites, splenomegaly
Upper G I Endoscopy: Portal hypertension, Grade II esophageal varices
Advice to : Stop DNS with MVI
Inj.Ondansetron was made sos
Inj.Pantoprazole stopped and T.Pantoprazole started
Ascitic fluid examination and continue the same treatment
63
Figure 34: patient with moderate ascites
Figure 35: swelling of lower limbs (edema)
64
Day 3:
BP: 100/70 mmHg Pulse: 80Bpm Weight: 49 kg
O/E
No fresh complaints
Icterus + , Fine tremors
Edema+, Platinychia+
Ascitic Fluid Analysis:
Morphology : 2.5 ml of straw colored fluid, containing 350 cells/mm3
of PMNs, few
macrophages, No meningial cells
Biochemistry:
Glucose: 128 (40-70mg/dl)
Protein: 2.2 (20-45mg/dl)
Chloride: 108( 116-122mg/dl)
Advice to : T.Chlordiazepoxide 25mg PO 0 -0-1
Repeat Platelet
Day 4 :
B.P:120/70 mmHg Pulse:88 BPM Weight: 46 kg
O/E:
Icterus+, hepatomegaly+,
Weakness, Decreased appetite.
Advise :
Discharge.
Inj.Vitamin K and inj ondansetron stopped.
Prothrombin time: 13 sec
Follow up at OPD after 1 week.
65
Discharge Medications
T.Torosemide+spiranolactone 10 mg + 100 mg PO 1 -0-0 X 4 days
T.Propranolol 10mg PO 1 -0-1 X 7 days
T.Chlordiazepoxide 25 mg PO 0 -0-1 X 1 week
T.Amoxicillin+Clavulanicacid 625 mg PO 1 -0-1 X 2 days
T.L-Ornithine -l-aspartate 500mg PO 1 -0-1 X 1 week
T.Pantoprazole 40 mg PO 1 -0-0 X 1 week
Pharmaceutical Care Plan
Subjective
Vomiting
Hepatomegaly
Splenomegaly
Abdominal distension
Pedal edema
Objective
Elevated: Bilirubin
AST
ALT
ALP
Decreased Albumin
• USG Abdomen
• Upper G I Endoscopy
Final Diagnosis:
Cirrhosis with Portal Hypertension, Ascites and Hepatic Encephalopathy .
66
Goals of therapy:
Identify and eliminate cause of cirrhosis.
Improve the signs and symptoms.
Prevention of further complications.
To maintain health related quality of life.
Treatment options:
1. Management of Portal Hypertension & Varices
Primary Prophylaxis
Non selective Beta blocker : Propranolol , Nadolol , Nitrates.
2. Treatment of Variceal bleeding : Somatostatin , Octero tide
EIS: Ethanolamine, sodium tetradecyl sulfate, sodium morrhuate
EBL
3. Prevention of re -bleeding : Propranolol, Nadolol
4. Management of Ascites:
5. Diuretic therapy : Spiranolactone, furosemide
6. Liver transplantations
7. Spontaneous Bacterial Peritonites : Cefotaxi me, Oral ofloxacin, Amoxicillin
8. Hepatic Encephalopathy Lactulose Metronidazole, Neomycin
67
Figure 36: portohepatic stent application
http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf
Goals Achieved :
Signs and symptoms were relieved
Patient was convinced to stop alcohol
Monitoring Parameters :
Liver function tests
Complete haemogram & Serum electrolytes
USG Abdomen
Ascitic fluid examination
G I Endoscopy
Renal Functions
Problems Identified :
• Untreated indication: Anemia
• Input output chart was not maintained
Patient Counseling
About Diseases :
• About signs and symptoms
• About complications
About medications :
• Medication adherence
• About missed dose
68
• Don’t take any OTC medication.
About Life style modifications :
• Stop taking Alcohol and smoking cessation
• Take nutritious diet (Restrict Protein diet)
• Restrict salt and water intake
69
Conclusion
The most common cause of portal hypertension is alcoholic cirrhosis.
Liver disease demonstrates a sex predilection, with males making up more than 60% of
patients with chronic liver disease and cirrhosis.
The most common initial symptom is hematemesis due to esophageal varices.
Portal hypertension can be diagnosed in sev eral ways. Clinical diagnosis can be made in
the setting of end -stage liver disease and in the presence of ascites and/or varices.
The main treatment is symptomatic , varices ( endoscopic therapy ), ascites (paracentesis)
, shunts to avoid further complica tions and worsening of the patient’s condition.
Portal hypertension is a complication of an underlying liver disease. It is a disease that
can be controlled but requires patients to be compliant with dietary restrictions and to
abstain from alcohol and dru gs. Survival rates can be quite high as long as some liver
function is maintained. The worse the liver function, the worse the prognosis.
70
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