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C linical S ignificance ......................................................................................................................... 159
Palliative Treatment
Palliative resection of large metastases in the liver is useful
if this can be accomplished without major lobectomy.
Otherwise, regional or systemic chemotherapy is used.
Long-term octreotide therapy provides effective symptomatic relief. There is no evidence that somatostatin
therapy shrinks the tumor.
Other Tumors
Several other rare tumors of the GEP system have been
reported, including:
1. PPoma. This tumor of the pancreas secretes PP, which
produces no symptoms. Consequently, these tumors
may be considered nonfunctional unless PP is
measured.
2. GRFoma. This tumor secretes growth hormone-releasing factor and causes acromegaly.
3. ACTHoma. This tumor secretes ACTH and causes
Cushing’s syndrome.
4. Neurotensinoma. This tumor secretes neurotensin and
causes diarrhea, hypotension, flushing, cyanosis, and
hypokalemia.
DIAGNOSTIC USES OF GI PEPTIDES
Several GI peptides are useful in the diagnosis of disease,
as adjuncts in radiology and endoscopy and in radionuclide imaging including in vivo receptor imaging.
Provocative Testing
Radioimmunoassay techniques have allowed for easier
diagnosis of peptide-secreting tumors, which often
demonstrate elevated levels of the peptide or peptides
secreted. When the diagnosis is equivocal, some GI
peptides are effectively used in provocative tests:
Secretin Test
The secretin test was described earlier as the most specific
test for ZES. A bolus intravenous administration of
secretin (2U/kg) causes paradoxical elevation in plasma
gastrin levels only when a gastrinoma is the cause
of hypergastrinemia. An elevation of 100 pg/mL over the
basal level is considered positive.
Pentagastrin Provocative Test
Pentagastrin, a synthetic analogue of gastrin, when given
by intramuscular injection (2mg/kg), causes discharge
of secretory products from carcinoid tumors. Following
pentagastrin administration, diagnostic elevation in
circulating serotonin or urinary 5-HIAA may occur. The
pentagastrin provocative test is an important diagnostic
maneuver in patients with MEN-2 syndrome, where
release of calcitonin is stimulated.
Uses in Radiology and Endoscopy
Glucagon is used to relax the duodenum for detailed contrast studies. Glucagon has replaced the use of local anesthetic to cause duodenal ileus for examination. Glucagon
is also useful in intraoperative cholangiography in order
to relax the sphincter of Oddi, allowing contrast to enter
the duodenum. When dye will not enter the duodenum,
this test distinguishes between spasm and a stone at the
terminal end of the common bile duct as the cause. The
use of glucagon also helps in cannulation of the papilla in
performing endoscopic retrograde cholangiopancreatography (ERCP).
Use in Radionuclide Imaging and
Radioreceptor Studies
125
I-octreotide, the labeled long-acting analogue of
somatostatin, helps to localize peptide-secreting tumors.
Some 50% to 60% of gastrinomas, insulinomas, VIPomas,
and carcinoids have a sufficiently high density of somatostatic receptors that they can be visualized with a gamma
camera after administration of labeled octreotide.
125
Ioctreotide could also be given immediately preoperatively,
and the pancreas and retroperitoneum can be scanned by
a hand-held gamma camera to localize peptide-secreting
tumors at operation.
125
I-octreotide binding to tissue in biopsy specimens
can provide useful information about the responsiveness
of the tumor to somatostatin therapy.
THERAPEUTIC USES OF GI PEPTIDES
The best-established peptidomimetic therapy in the GI
tract is the use of octreotide in controlling symptoms
caused by peptides secreted from apudomas. The beneficial action of octreotide arises from its ability to inhibit
both the release of peptides from tumors and their action
on target cells. A large body of experience now exists to
show that octreotide therapy is effective in controlling
diarrhea and flushing in over 80% of patients with
VIPomas and carcinoids. Octreotide is also effective in
controlling the dermatitis of glucagonoma in most
patients. It controls the symptoms of insulinoma in about
60% of patients. In all these cases, while improvement in
symptoms is accompanied by a drop in the circulating
level of peptide, improvement is greater than can be
inferred from the decrease in peptide release. This is,
of course, because somatostatin inhibits the action of
whatever peptide is released.
Although somatostatin does possess antitrophic action
in vitro, its use in vivo has not been associated with
decrease in tumor size to any significant degree.
Bombesin (GRP) is a potent growth factor in small cell
lung cancer. Monoclonal antibodies to bombesin have
been used in treatment of patients with this tumor, and
significant tumor regression has been observed. Powerful
CCK and gastrin receptor antagonists have been
developed. It is likely that these may, in the future, have
therapeutic application.
CGRP is important in mediating gastric mucosal cytoprotection and in preventing stress- and NSAID-related
ulcers. These actions of CGRP are likely to be applied in
therapeutic strategies in the future.
Peptide Growth Factors in the GI Tract
Several peptides play an important role in regulating proliferation in gastrointestinal mucosa (Table 5.15). These
peptides are important in the regulation of mucosal cell
and mesenchymal cell proliferation, fetal development,
regeneration of mucosal defects or organs, and in angiogenesis. Some may also play a role as autocrine growth
factor for human colon cancer.
Depending on the proximity of their release to the
target cell, they may be autocrine (controlling the cell that
TABLE 5.15. Peptide Growth Factors of the Gastrointestinal
Tract
Peptides Growth Effects
EGF family Increased cell proliferation
EGF Increased insulin synthesis
TGF-a Increased food intake
HB-EGF Angiogenesis
TGFb Family Inhibition of cell proliferation
Production of collagen, fibronectin,
laminin
Increased insulin synthesis
IGF Family Stimulation of cell proliferation and
IGF-I mucosal growth
IGF-II Autocrine growth of human colon cancer
Fetal growth of GI tract
Autocrine growth of human colon cancer
FGF Family Neovascularity
bFGF Proliferation of fibroblasts
aFGF Post-mucosal injury repair
Hepatocyte growth Liver regeneration
factor Renal development
Epithelial and mesenchymal cell migration
Others
Hematopoietic stem Integration of leukocyte production
cell factors
PDGF Mitogen for fibroblasts and
mesenchymal cells
Trefoil peptides Regulation of mucosal proliferation
FIGURE 5.16. Simplified depiction of the actions of peptide
growth factors. Binding of growth factors to specific transmembrane proteoglycan receptors results in the release of second
messengers (cAMP, cGMP, IP3, calcium), which activate nuclear
transcription factors (jun, fos, erg, e-myc, NFKb). The nuclear
transcription factors then mediate cell growth.
produces them), paracrine (reaching the target cell by diffusing through interstitial tissue), or endocrine (reaching
the target cell via the circulation). Key to the mechanism
of their action is ligand-receptor binding. Generally, two
receptor types mediate their function: transmembrane
receptors or extracellular proteoglycan side chains of different receptors. Signaling mechanisms include adenylate
cyclase-generated cAMP, the inositol pathway and
calcium, and the products of protein kinase C. Ultimately,
they must modulate cellular proliferation through the
alteration of transcription of various genes. Figure 5.16
provides a highly simplified depiction of these processes.
All these peptides exert growth effects outside the GI
tract except the trefoil peptides, which seem to be specific
to the GI tract. Trefoil peptides have two functions: In
basal circumstances they play a role in mucus stabilization;
when an acute injury occurs, they are rapidly upgraded
and stimulate the repair process, particularly epithelial
restitution. The effects on epithelial cells are closely
integrated with effects in extracellular matrix, and each
may have a regulating effect on the other.
Recently, a novel gastric hormone, ghrelin, has been
shown to be an endogenous ligand for the growth
hormone secretagogue receptor (GHSR) that can stimulate growth hormone release. Ghrelin is somatotrophic,
orexigenic, and adipogenic and thus plays a role in the regulation of growth and energy balance.
REFERENCES
Abbreviations: aFGF, acid fibroblast growth factor; bFGF, basic fibroblast
growth factor; EGF, epidermal growth factor; HB-EGF, heparin-binding EGF;
HGF, hepatocyte growth factor; IGF, insulin growth factor; PDGF, plateletderived growth factor; TGF, transforming growth factor.
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160 ............................................. Gastrointestinal P eptides and Peptide-Secreting T umors (Apudomas)
S uggested R eadings............................................................................................................................. 161
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SELECTED READINGS
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6.
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in controlling appetite and food intake in humans. Peptides
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119–139.
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and diagnosis: an overview. Chemotherapy 2001;47(Suppl 2):
1–29.
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2002;34:102–108.
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of gastrin receptors in human colon cancers. Cancer Res 1989;
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162 ...........................................................................................................................................................
EMBRYOLOGY
The liver, the biliary tree, and the pancreas develop from
a diverticulum of the foregut of the 3-mm embryo. This
diverticulum has three buds. The caudal bud forms the
pancreas, the cranial bud gives rise to the liver, and
the middle bud forms the gallbladder. The ventral bud
begins as a hollow tube but soon becomes a solid mass
within which biliary ducts form by a process of canalization. The hepatocytes line small biliary canaliculi, which
drain into larger ducts and then into the lobar ducts. The
lobar ducts, in turn, drain into the right and left hepatic
ducts.
SEGMENTAL ANATOMY
Traditionally, the insertion into the liver of the falciform
ligament was thought to divide the liver into a right and a
left lobe. In 1981, Couinaud provided a more accurate
description of the segmental anatomy of the liver (Figure
6.1).
1
The true division into a right and a left lobe lies in
the main lobar fissure, an oblique plane passing from the
gallbladder fossa anteriorly to the bed of the inferior vena
cava posteriorly (Cantile’s line). Thus, the portion of the
liver between the main lobar fissure and the falciform ligament represents the medial segment of the left lobe, while
the traditional left lobe is the lateral segment of the true
(i.e., anatomic) left lobe. A right segmental fissure divides
the right lobe into anterior and posterior segments.
6
Liver
SURGICAL ANATOMY
BILE DUCT ANATOMY
Each of the nine segments of the liver is drained by a segmental duct. In the right lobe, the ducts of the right anterior and right posterior segments join to form the right
hepatic duct. In the left lobe, the segmental ducts of the
medial and lateral segments unite to form the left hepatic
duct. The right and left hepatic ducts join at the hilum of
the liver to form the common hepatic duct.
BLOOD SUPPLY
The vasculature of the liver has three important components, that is, the hepatic artery, the portal vein, and the
hepatic venous system.
Hepatic Artery
The common hepatic artery is a branch of the celiac axis.
After giving off the right gastric and gastroduodenal arteries, it ascends to the liver in the hepatoduodenal segment,
where it usually lies to the left of the common bile duct
and anterior to the portal vein. In 17% of individuals, the
right hepatic artery originates not from the celiac axis but
from the superior mesenteric artery. The hepatic artery
branches into the cystic artery and, at the hilum of the
liver, divides into a left and a right hepatic artery. The
hepatic arteries carry oxygenated blood and provide 25%
of the total blood supply to the liver.
The liver is the only organ in the abdomen without which life cannot be sustained. The
liver is a master organ for its role in metabolism, excretion, and synthesis. In surgical
practice, its importance lies not only in the surgical management of treatable liver disorders
such as end-stage liver disease but also in sustaining adequate function to enable the conduct
of all anesthesia and all surgical procedures and to maintain blood coagulability and
hemostasis.
FIGURE 6.1. Segmental anatomy of the liver, based on Couinaud.
1
Portal Vein
The portal vein accounts for 75% of the blood supply of
the liver, but its blood has an oxygen saturation of only
60%. The portal vein originates from the confluence of the
superior mesenteric and splenic veins, posterior to the
neck of the pancreas. It reaches the liver in the hepatoduodenal ligament, where it lies behind the common bile
duct and hepatic artery. In the porta hepatis, the portal
vein divides into right and left branches, which continue
to their respective hepatic lobes. The portal vein possesses
no valves.
Hepatic Venous System
Knowledge of the hepatic venous system anatomy is
crucial to the performance of hepatic lobectomy. Venous
blood from hepatic lobules drains into the sinusoids and
then into the central veins. Central veins join to form
sublobular veins and then collecting veins.Collecting veins
coalesce to form three major hepatic veins (Figure 6.2):
1. The right hepatic vein, which drains all of the posterior segment and part of the anterior segment of the
right lobe.
FIGURE 6.2. Anatomy of the hepatic venous system.
S urgical A natomy................................................................................................................................ 163
164 ................................................................................................................................................. Liver
2. The middle hepatic vein, which drains the inferior area
of the medial and anterior portions of the two lobes.
3. The left hepatic vein, which drains the entire area to
the left of the umbilical fissure.
Hepatic venous pressure is approximately 8mm Hg;
total blood flow through the hepatic veins is approximately 1500mL/min/1.73 m
2
of body surface.
LYMPHATIC DRAINAGE
A significant portion of the lymphatic drainage of the liver
collects in the subcapsular area, from which it passes in
lymphatic channels through the diaphragm and suspen-
sory ligaments of the liver into the posterior mediastinal
nodes. A smaller portion of the lymphatic drainage either
accompanies the hepatic veins or drains to the porta
hepatis along the portal venous system.
NERVE SUPPLY
The liver has a rich sympathetic nerve supply derived from
ganglia T-7 to T-10. The parasympathetic innervation is
derived from the hepatic branch of the anterior vagus
nerve and from the celiac branch of the posterior vagus
nerve. From the celiac ganglia, both sympathetic and
parasympathetic fibers travel to the liver in the adventitia
of the hepatic arteries.
The major functions of the liver include metabolism, bile
formation, inactivation and excretion, reticuloendothelial
system, and liver regeneration.
METABOLISM
The liver plays an important role in the metabolism of carbohydrates, lipids, and proteins.
Carbohydrate Metabolism
A key function of the liver is to maintain normal blood
glucose levels. Between meals, it exports 10 g of glucose per
hour. Several hepatic processes are important in carbohydrate metabolism:
1. Glycogen storage. All hexose sugars that do not enter
the glycolytic pathway are converted into glycogen and
stored. Insulin promotes glucose storage as glycogen.
2. Glycogenolysis. In times of hypoglycemia, glycogen
is converted into glucose by the action of catecholamines
and/or glucagon to rapidly restore blood glucose. This
requires the enzyme glucose-6-phosphatase. Absence of
the enzyme causes glycogen storage diseases.
3. Glycolysis. This is the process by which glucose is
phosphorated to enter Krebs cycle, which generates highenergy phosphates and lactate.
4. Gluconeogenesis. This is the reverse of glycolysis, by
which glucose is synthesized from lactate/pyruvate and
amino acids.
Lipid Metabolism
Lipoprotein complexes absorbed from the gut are captured by the cathrin-coated pits of hepatocytes and inter-
nalized. The lipid thus taken up into the hepatocyte may
be used for one of two purposes:
1. Secretion into the space of Disse as very low density
lipoprotein (VLDL) or low density lipoprotein (LDL)
or
2. Generation of fatty acids and acetyl-coenzyme A
(acetyl CoA).
Protein Synthesis
Most plasma proteins except immunoglobulins are synthesized by the hepatocyte. These plasma proteins include
albumin, transferrin, and lipoproteins.Also synthesized by
the hepatocytes is the group of peptides involved in the
coagulation cascade. These include Factors II, VII, IX, and
X. Only Factor VIII, the anti-hemophiliac factor, is produced not by hepatocytes but in vascular endothelium.
The liver also produces fibrinogen and antiplasmin. Thus,
liver failure can lead to hypoprothrombinemia, which,
when severe, can lead to fibrinolysis and disseminated
intravascular coagulopathy (DIC).
BILE FORMATION
Albumin-bound bilirubin is carried into the hepatocyte,
where it is made water soluble by the addition of glucuronide, and catalyzed by uridine diphosphonucleotide
glucuronyl transferase (UDPGT). The soluble bilirubin is
transported into the bile canaliculus. The hepatocyte
also oxidizes cholesterol to form cholic acid and chenodeoxycholic acid, two primary bile acids that are important in micelle formation. The rate of formation of these
bile acids is governed by the enterohepatic circulation,
with the return of bile salts acutely stimulating the
PHYSIOLOGY OF THE LIVER
production of bile, that is, bile salt-dependent bile secretion. Cholesterol and lecithin are also secreted in the bile.
Bile acids and lecithin form micelles, which carry cholesterol in micellar core, thus solubilizing it and preventing
its deposition as stone. An additional substance released
into the bile by the hepatocytes is immunoglobulin A. The
bile delivered by the hepatocyte into the bile canaliculi is
isotonic. The epithelium of the bile ductules adds bicarbonate to the bile under the influence of secretin and VIP.
INACTIVATION AND EXCRETION
The liver is an important organ for inactivating drugs and
toxins, which are then excreted into the bile. Because the
liver is also important for drug metabolism, dosage of any
drug must be adjusted in treating liver disease. In addition,
some drugs may inhibit the hepatic enzymes needed to
metabolize other drugs, a problem that may cause dangerous drug interactions. An example is the combination
of Coumadin® and the H
2
-receptor antagonist cimetidine.
Cimetidine inhibits P-450 and, in turn, inhibits the degradation of Coumadin®. This can precipitate hemorrhage.
RETICULOENDOTHELIAL
SYSTEM FUNCTION
The reticuloendothelial system (RES) of the liver is
thought to function as an important filtration system,
removing bacteria and endotoxin that may be translocated
from the gut. Kupffer cells are thought to remove as
much as 99% of bacteria from portal blood. The RES also
inactivates small gastrointestinal peptides and amines,
thus protecting the systemic circulation. The carcinoid
syndrome develops when this hepatic degradation of
amines is bypassed, allowing them to enter the systemic
circulation.
HEPATIC REGENERATION
The liver has remarkable regenerative capacity, as evidenced after major liver resection or hepatocyte destruction by toxins or viral hepatitis. The capacity of the liver
to regenerate permits the use of the right lobe for liver
transplantation. The major hepatic growth factors important in regeneration include epidermal growth factor
(EGF), transforming growth factor-a (TGF-a) and the
hepatocyte growth factor (HGF). For these growth factors
to initiate growth, a certain amount of liver must be
resected (70% in rats) or a certain number of hepatocytes
must be destroyed. Once this condition is present, TGF-a
or HGF induce the crucial transcription factors of c-jun
and NFK-b.
CIRRHOSIS
Liver injury from several causes may lead to hepatic fibrosis and cirrhosis. The process has been studied best in
alcoholic liver disease. Approximately 10% of alcoholic
patients will develop cirrhosis. The central mechanism of
fibrosis involves stimulation of the perisinusoidal or stellate cells, which reside in the space of Disse. The stellate
cell becomes actively proliferative and changes into a
myofibroblast-like cell that produces collagen. Collagen
deposition causes perisinusoidal fibrosis. The known stimulants for the stellate cell include acetaldehyde, products
of lipid peroxidation, and TGF-b. Once stellate cells are
activated, they produce TGF-b.
Other types of cirrhosis include: (1) postnecrotic cirrhosis, which may follow liver destruction by viral infection or toxins; (2) biliary cirrhosis, which results from
prolonged biliary obstruction; (3) cirrhosis associated
with hemochromatosis, due to iron load; and (4) cirrhosis associated with Wilson’s disease, due to abnormal
copper metabolism.
In all types of cirrhosis, it is necessary to have criteria
for assessing hepatic functional reserve, the most common
of which are those promulgated by Child (Table 6.1).
FULMINANT LIVER FAILURE
Fulminant liver failure is an emergency characterized by
rapid development of severe hepatocellular dysfunction,
PATHOPHYSIOLOGY
TABLE 6.1. Child’s Classification of Hepatic Functional Reserve
Level of Function Class A Class B Class C
Serum bilirubin <2 2–3 >3
(mg/dL)
Serum albumin (g/dL) >3–5 3–3.5 <3
Ascites None Medically Poorly
controlled controlled
Neurological signs None Minimal Severe or coma
Nutrition Excellent Good Poor
P athophysiology ................................................................................................................................. 165
166 ................................................................................................................................................. Liver
encephalopathy, cerebral edema, and coma. Jaundice and
coagulopathy are important manifestations. The most
common causes are drugs and hepatotropic viruses. The
drug that most commonly causes liver failure is acetaminophen in doses of 4 g or more per day. Other associated drugs include halothane, sulfonamides, phenytoin,
isoniazid, and valproic acid. The most important viral
causes are hepatitis A and B. Fulminant liver failure can
also be caused by acute ischemia and primary graft nonfunction during liver transplantation.
Major complications of fulminant liver failure include
hypoglycemia, cerebral edema, sepsis, hemorrhage from
coagulopathy or stress ulceration, hypotension, and respiratory and renal failure. Renal failure may occur as a result
of hypovolemia, hepatorenal syndrome, or acute tubular
necrosis.
Management includes:
1. Blood glucose and intracranial pressure monitoring
and treatment.
2. Surveillance for infection and immediate antibiotic
therapy when detected.
3. Avoidance of benzodiazepines and sedatives.
4. H
2
-receptor antagonist therapy.
5. Monitoring of coagulation and administration of
vitamin K, platelets, and fresh frozen plasma; monitoring and normalizing hemodynamic parameters.
6. Mechanical ventilation and hemofiltration or renal
dialysis when necessary.
With intensive medical care, the high mortality rate of
fulminant liver failure has improved modestly. Only liver
transplantation, however, has allowed the salvage of
patients with irreversible fulminant hepatic failure. As a
bridge to recovery or liver transplantation, other devices
have been used, including bioartificial liver devices, nonhuman liver, and hepatocyte transplantation. All of these
bridge treatments are now experimental.
HEPATORENAL SYNDROME
Hepatorenal syndrome (HRS), defined as renal failure in
the setting of cirrhosis or severe liver disease but in the
absence of intrinsic renal disease, is characterized by
intense vasoconstriction in the renal cortex. The incidence
of HRS in cirrhosis with ascites has been reported to range
from 18% to 35%.
2
The pathogenesis of HRS is believed to be peripheral
arterial vasodilatation due to nitric oxide, glucagon, substance P, CGRP, and insulin; it leads to reduction of effective circulating volume. Decreased renal perfusion leads to
increased renal vascular resistance as well as sodium
and water retention involving the renin-angiotensinaldosterone mechanism, the sympathetic nervous system,
vasopressin, endothelin, and leukotriene E
2
.
PORTAL HYPERTENSION
Portal hypertension arises when portal venous pressure
exceeds hepatic venous pressure by 8 mm Hg. Normal
portal vein pressure is 7 to 10mm Hg. In portal hypertension, portal pressure averages about 20 mm Hg but can
occasionally rise to 50mm Hg or greater. The portal vein
has no valves; therefore, any increase in portal pressure is
reflected back to the tributaries, causing varices at all sites
of portasystemic anastomosis. The essentials of portal
hypertension are summarized in Table 6.2.
Pathogenesis of Portal Hypertension
Portal pressure can rise due to: (1) increased resistance
within the portal circulation and (2) increased portal
blood flow. Worldwide, the most common cause of portal
hypertension is schistosomiasis, with the exception of
North America, where alcoholic cirrhosis is the most
common cause. Causative factors are classified and listed
in Table 6.3.
TABLE 6.2. Essentials: Portal Hypertension
Primary Location Disorder
Causes
Prehepatic Portal vein thrombosis
Intrahepatic Cirrhosis
Posthepatic Hepatic vein/IVC
thrombosis
Primary Disorder Treatment Options
Complications
Acute variceal Endoscopic sclerotherapy
hemorrhage or ligation
Pharmacologic (pitressin,
somatostatin)
Balloon tamponade
TIPS
Emergency portocaval
shunt
Recurrent variceal Endoscopic obliteration
hemorrhage of varices
Portocaval shunt
Distal splenorenal shunt
Mesocaval shunt
TIPS and liver
transplantation
Ascites Medical therapy (low
sodium diet,
spironolactone)
Peritoneovenous shunt
TIPS
Side-to-side portocaval
shunt
Liver transplantation
Abbreviations: IVC, inferior vena cava; TIPS, transjugular intrahepatic
portasystemic shunt.
TABLE 6.3. Causative Factors of Portal Hypertension
Increased resistance to flow
Prehepatic
䊏
Portal vein thrombosis
䊏
Splenic vein thrombosis
䊏
Cavernous transformation of portal vein
䊏
Congenital atresia of portal vein
Hepatic
䊏
Cirrhosis
Alcoholic
Postnecrotic
Biliary
Hemochromatosis
䊏
Schistosomiasis
䊏
Acute alcoholic liver disease
Posthepatic
䊏
Budd-Chiari syndrome
Hepatic vein thrombosis
Inferior vena cava thrombosis
䊏
Constrictive pericarditis
Increased portal blood flow
䊏
Traumatic arterioportal venous fistula
䊏
Splanchnic arteriovenous fistula
Increased Resistance
EPATIC CAUSES Cirrhosis and schistosomiasis are the
H
primary causes. Resistance to flow is caused by intrahepatic
obstruction, which may be predominantly presinusoidal,
sinusoidal or postsinusoidal (Figure 6.3). Obstruction
often occurs at more than one level. Presinusoidal obstruction, which takes place at the presinusoidal level, causes
increased portal pressure proximal to the sinusoids and
normal or decreased sinusoidal pressure. When the block
is postsinusoidal, however, both sinusoidal and presinusoidal (portal) pressures rise. Increased sinusoidal pressure
leads to the formation of large amounts of lymph, causing
ascites. Thus, ascites is not a major feature of presinusoidal
block—or even of sinusoidal block—but is prominent
when the obstruction is either postsinusoidal or in the
hepatic vein.
Schistosomiasis causes predominantly presinusoidal
block, but alcoholic and postnecrotic cirrhosis cause both
sinusoidal and postsinusoidal block.
OSTHEPATIC CAUSES Budd–Chiari syndrome is a rare
P
disorder resulting in hepatic vein thrombosis. In some
patients the cause is unknown. In many patients, however,
there is associated polycythemia vera or a history of oral
contraceptive use. Constrictive pericarditis (e.g., tuberculosis) can also cause the syndrome.
Increased resistance may be caused by prehepatic, hepatic,
or posthepatic factors.
REHEPATIC CAUSES Portal vein thrombosis is
P
common in children due to umbilical vein sepsis. In adults
it is rare but may be caused by malignancy, pancreatitis,
or as a consequence of pylephlebitis. While portal vein
thrombosis may cause portal hypertension, liver function
is usually maintained and ascites is uncommon. Splenic
vein thrombosis occurs in the course of pancreatitis or is
caused by neoplasms. The resulting hypertension is located
in the venous bed drained by the splenic vein (left-sided
portal hypertension), which leads predominately to gastric
varices.
Increased Portal Blood Flow
The primary cause of increased hepatopetal flow resulting
in elevated portal pressure is the formation of arteriovenous fistulas between the hepatic artery and portal vein or
between the splenic artery and splenic vein. The main
cause of arteriovenous fistula formation is trauma, including operative trauma. Another cause of increased
hepatopetal flow is increased splenic blood flow due to
Banti’s syndrome or other conditions associated with
splenomegaly.
FIGURE 6.3. Hepatic causes of portal hypertension and ascites.
P athophysiology ................................................................................................................................. 167
FIGURE 6.4. The major sites of portasystemic anastomosis, where varices can develop as collaterals
between the portal and systemic circulations.
Consequences of Portal Hypertension
Clinically significant consequences of portal hypertension
include varices, splenomegaly, ascites, encephalopathy, and
hepatic coma.
Collateral formation is different in prehepatic and
hepatic portal hypertension. In prehepatic hypertension,
collaterals form in the diaphragm and in the hepatogastric
and hepatocolic ligaments. They form to bypass the
obstruction in the portal vein and carry blood to the liver;
in other words, they are hepatopetal. In hepatic causes of
Formation of Varices
Varices develop as collaterals between the portal and systemic circulations (Figure 6.4). The major sites of portasystemic anastomosis include the lower end of the
esophagus (esophageal varices), the umbilical vein (caput
medusa), the hemorrhoidal plexus (hemorrhoids),
and retroperitoneal collaterals through lumbar veins
portal hypertension, however, the collaterals serve to
decompress the liver by carrying blood away from it, that
is, they are hepatofugal. Hepatofugal flow tends to create
esophageal and gastric varices. Bleeding from esophageal
varices is a major complication of portal hypertension. Less commonly, bleeding can also occur from
hemorrhoids.
(retroperitoneal varices).
168 ................................................................................................................................................. Liver
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