surgical diseases of liver

8/11/2019 surgical diseases of liver

1/83


2/83

!EVE"#$%ENT #& 'E$T#)I"I*+ S,*E*+

Surgeons have learned to operate successfull on the liver primaril during the past three

decades. &or centuries/ the liver 0as a msterious organ 0ith comple anatom/ an

over0helming num2er of functions/ and an etraordinar capa2ilit to regenerate. Theorgan3s large si4e and a2undant 2lood suppl contri2uted to the respect paid to this organ in

most civili4ations and operating theaters. Improved understanding of anatom and

phsiolog/ com2ined 0ith a num2er of recentl developed surgical techni5ues/ led from

mth and mster to the emergence of the specialt of hepato2iliar surger.

"aparoscopic cholecstectom rivals "angen2uch3s contri2ution of the open techni5ue (he

performed the first successful cholecstectom in 1667 0ith respect to surgical

importance. Not onl has laparoscopic cholecstectom opened the field to other ne0

procedures/ laparoscopic surger has contri2uted greatl to present interest in shortened

hospital stas/ lessened costs/ and the rethinking of surgical dogma such as 0ide eposure.The development of hepato2iliar surger culminates in the rise and increased safet of

hepatic resections and liver transplantation. large num2er of hepatic resections are

performed 2 speciali4ed surgeons in ma8or centers. The mortalit of elective resection has

decreased from 79: t0o decades ago to less than 1:. This increased safet follo0s

improved technolog and understanding of the anatom and phsiolog of the liver. ;ith

improved safet has come an increased confidence in liver surger/ a 0ide epansion of the

indications for resection/ and development of other aggressive procedures such as

croa2lation and chemoem2oli4ation. The most common indication for partial liver

resection in most centers remains neoplasia.

spectacular advance in hepatic surger and hepatic therap in general has 2een the

success of liver transplantation. ;elch performed the first eperimental liver transplant in

1


3/83

surger. It is likel the net decade 0ill see consolidated educational programs for the

training of phsicians and surgeons in this field. unified International 'epato-$ancreato-

)iliar ssociation has led to the development of the merican 'epato-$ancreato-)iliar

ssociation ('$)/ 0hich promotes a union of surgeons/ gastroenterologists/

radiologists/ and other specialists 0ho 0ork 0ithin this dnamic field.

I. NT#%+ N! $'+SI#"#+

NT#%+ N! $'+SI#"#+

%odern concepts of gross hepato2iliar anatom differ considera2l from the anatom

suggested 2 the ligamentous reflections of the peritoneum/ particularl the falciform

ligament. &or centuries the right lo2e of the liver 0as defined as all the hepatic parenchma

to the right of the falciform ligament and the left lo2e as onl the su2stance to the left of

the ligament. There are no0 t0o ne0 classifications of the gross anatom that have much

more applica2ilit to surger. The first is the lo2ar sstem used most fre5uentl in the,nited States and often called the merican Sstem. The second is the &rench segmental

sstem/ 0hich has the most applica2ilit.

natomic features that ena2le the liver to 2e an important integrator 2et0een the digestive

sstem and the rest of the 2od include (1 a dual 2lood suppl/ 0ith portal 2lood from the

splanchnic sstem and the hepatic arterB (7 a specific architectural arrangement of single

cells and cell masses that facilitates echange 2et0een 2lood and hepatoctesB (@ a

specific orientation of the hepatoctes that compartmentali4es 2iliar versus 2lood

path0asB and ( an organi4ed 2iliar ecretor sstem that regulates the enterohepatic

circulation. In this section aspects of the anatomic organi4ation of the liver are considered

that are important for 2oth hepatic phsiolog and surger.

ross natom

eneral !escription

The liver lies in the right upper 5uadrant of the a2domen/ 2eneath the diaphragm and

connected to the digestive tract 2 means of the portal vein and the 2iliar drainage sstem.

The largest gland in the 2od/ it 0eighs approimatel 1=99 gm. in the adult . The liver

accounts for 7: of the 2od 0eight of the adult and a2out =: of the 2od 0eight of a

ne02orn. 'epatic etramedullar hematopoiesis produces the relativel larger liver si4e in

ne02orns. The normal adult liver resides under the protective ri2 cage. It etends in the

midclavicular line from as high as the fourth intercostal space do0n to slightl 2elo0 thecostal margin. The gall2ladder lies on the dorsal surface of the liver in a transploric plane.

peritoneal mem2rane (lisson3s capsule covers the liver and etends as fi2rous septa

into the parenchma 0ith 2lood vessels and 2ile ducts. The superior surface of the liver

conforms to the undersurface of the right diaphragm. #nl the liver to the left of the

falciform ligament contacts the left diaphragm. The inferior surface of the liver touches the

duodenum/ colon/ kidne/ adrenal gland/ esophagus/ and stomach. $eritoneum invests the

entire liver ecept for a 2are area under the diaphragm on the posterosuperior surface

ad8acent to the inferior vena cava and hepatic vein.

Normal !evelopmentThe liver primordium appears at a2out the third 0eek as a ventral thickening of the

entoderm at the distal end of the foregut (future duodenum. The ma8or portion of this


4/83

primordium produces hepatic parenchma and the main 2ile duct. secondar caudal

proliferation 0ill 2ecome the gall2ladder and cstic duct. The hepatic primordium is

formed of cellular cords/ 0hich coloni4e the ventral mesogastrium (septum transversum.

The vitelline (omphalomesenteric veins connected to the digestive tu2e consist of an

anastomotic net0ork around the duodenum and then cross the septum transversum.

$roliferation of the entodermal cords forming the hepatic primordium fragments thevitelline veins into a vascular la2rinthD the hepatic sinusoids. The hepatoctes arrange

themselves into cords surrounding the sinusoidal capillaries.

;hen the olk sac disappears/ the vitelline veins regress almost totall and persist onl in

their mesenteric 2ranches. Caudad to the liver/ the anastomotic net0ork of vitelline veins

fuse into a single trunk/ the portal vein. In a cranial direction the vitelline veins open into

the sinus venosus. ;hen the left horn of the sinus venosus disappears/ the right vitelline

trunk receives the anastomosis of the inferior vena cava and 2ecomes the terminal segment.

Etension and proliferation of hepatoctes into the entire septum transversum result in

concurrent fragmentation of the um2ilicoallantoic veins (more lateral to the vitellineveins. The right um2ilicoallantoic vein regresses in the sith 0eek/ leaving the left one to

drain 2lood coming from the placenta to the liver. The left um2ilical vein drains into the

left portal vein and passes through a temporar/ short circuit (ductus venosus directl into

the inferior vena cava. The ductus venosus and left um2ilical vein are o2literated after 2irth

to form the ligamentum venosus and the ligamentum teres.

The hepatoctes proliferate/ and the liver protrudes from the transverse septum into the

a2domen/ 0ith the 2are area a reminder of its origin. )ile ducts differentiate from hepatic

cells and 8oin the etrahepatic 2iliar sstem/ appearing first in the hilum and then

spreading peripherall. )ile formation ma 2e evident as earl as the third month.

Topographic natom

The reflections of peritoneum that attach the liver to the a2dominal 0all/ diaphragm/ and

a2dominal viscera determine the topographic anatom of the liver. Three sets of ligaments

include the follo0ingD

1. The falciform ligament/ 0hich attaches the liver to the anterior a2dominal 0all from the

diaphragm to um2ilicus and incorporates the ligamentum teres hepaticus in its dorsal

2order. In persons 0ith portal hpertension/ the um2ilical vein recanali4es and connects the

perium2ilical superficial venous sstem 0ith the portal sstem.

7. The anterior and posterior right and left coronar ligaments/ 0hich in continuit 0ith

the falciform ligament connect the diaphragm to the liver. The lateral aspects of theanterior and posterior leaves of the coronar ligaments fuse to form the right and left

triangular ligaments. The area encompassed 2 the falciform/ coronar/ and triangular

ligaments over the inferior vena cava and under the diaphragm is the 2are area of the liver.

@. The gastrohepatic and hepatoduodenal ligaments/ 0hich consist of the anterior laer of

lesser omentum and are continuous 0ith the left triangular ligament. The hepatoduodenal

ligament contains the hepatic arteries/ portal vein/ and etrahepatic 2ile ducts. It forms the

anterior 2oundar of the epiploic foramen of ;inslo0 and the communication 2et0een the

greater and lesser peritoneal cavities.

&our lo2es of the liver are commonl descri2edD right/ left/ 5uadrate/ and caudate. Thetopographic right lo2e includes a portion of the liver to the right of the falciform ligament

and the topographic left lo2e portion to the left. The 5uadrate lo2e is a rectangular 8unction


5/83

on the inferior surface 2ounded 2 the um2ilical fissure on the left/ the gall2ladder fossa on

the right/ and the portal triad posteriorl. The posterior (transverse etension of the

falciform ligament (ligamentum venosum on the left and the impression of the inferior

vena cava on the right delineate the caudate (spigelian lo2e.

"o2ar natom (The merican Sstem

The distri2ution of the ma8or 2ranches of the veins/ arteries/ or 2ile ducts of the liver doesnot conform precisel 0ith the topographic anatom . The general relationships 2et0een

the hepatic veins and portal vein 2ranches determine the lo2ar anatom of the liver/ 0hich

is 2est demonstrated 2 direct in8ection of its 2lood suppl 0ith su2stances such as

methlene 2lue or colored celloidin. plane called the portal fissure (Cantlie3s line passes

from the left side of the gall2ladder fossa to the left side of the inferior vena cava to divide

the liver into right and left lo2es. The left lo2e consists of a medial segment/ 0hich lies to

the right of the falciform ligament and um2ilical fissure/ and a lateral segment/ 0hich lies

to the left of the falciform ligament. The right lo2e consists of an anterior and a posterior

segment. No visi2le surface marking delineates the lo2ar segmental anatom.Conventionall/ most of the topographic caudate lo2e is in the medial segment of the left

lo2e/ 2ut it etends over the plane 2et0een the gall2ladder and the inferior vena cava into

the anatomic right lo2e. The conceptual division of the liver into lo2es and segments forms

the 2asis for the four classic tpes of ma8or hepatic resection . The lo2es ma 2e further

divided into su2segments that correspond to segments in the &rench sstem/ descri2ed

net.

&rench Segmental Sstem

nother nomenclatural sstem for hepatic anatom 0as developed 2 Soupault and

Couinaud. This sstem sho0s more consideration for the hepatic venous drainage and

caudate lo2e 2ut also applies to the portal/ 2iliar/ and arterial anatom. Instead of four/

there are eight segmentsD four on the right/ three on the left/ and one corresponding to the

topographic caudate lo2e. Segment I corresponds to the caudate lo2eB segments II to IV

constitute the left lo2eB and segments V to VIII the right lo2e. The three main hepatic veins

divide the liver into four sectors. The planes containing the right/ middle/ and left hepatic

veins are called portal scissurae/ 0hile the planes containing portal pedicles are called

hepatic scissurae. The caudate lo2e is its o0n autonomous segment in the &rench sstem.

In general/ the segments descri2ed in the &rench classification correspond to the

su2segments descri2ed in the lo2ar anatomic classification.

$ortal Vein

The portal vein provides a2out three fourths of the liver3s 2lood suppl. The 8unction of the

superior mesenteric and splenic veins forms the portal vein/ dorsal to the neck of the

pancreas. The portal vein then passes superiorl/ posterior to the first part of the duodenum

at the level of the second lum2ar verte2ra. This vein varies from 1 to @ cm. in diameter and

= to 6 cm. in length 2efore dividing into right and left 2ranches at the porta hepatis. In

a2out 19: of persons there appear to 2e three main trunks of the portal vein/ 0ith t0o

going to the right lo2e and one to the left lo2e. The etra trunk represents the right 2ranchof the portal vein dividing into segmental (sectoral 2ranches 2efore entering the liver. The

portal vein usuall passes 2ehind the 2ile duct and hepatic arter in the hepatoduodenal


6/83

ligament. The portal vein rarel varies. lthough the portal vein neatl divides into right

and left 2ranches/ it does not distri2ute splanchnic 2lood e5uall to the hepatic lo2es.

*adioactive phosphorus in8ected into the superior mesenteric vein preferentiall flo0s into

the right lo2e/ 0hereas splenoportograph demonstrates the t0o lo2es nonselectivel.

!espite the preferential flo0/ the t0o lo2es function similarl. 'o0ever/ the preferential

flo0 has pathologic significanceB for eample/ ame2ic a2scesses appear predominantl inthe right lo2e.

The portal trunk divides into left and right hepatic 2ranches in the portal fissure. The left

2ranch of the portal vein is longer and consists of t0o portionsD (1 the pars transversus/

0hich traverses the 2ase of segment IV/ and (7 the pars um2ilicus/ 0hich turns into the

um2ilical fissure. T0o 2ranches to the lateral segment of the left lo2e (segments II and III

usuall arise from the pars um2ilicus near the plane of the falciform ligament. )ranches

from 2oth the pars transversus and um2ilicus suppl the medial segment of the left lo2e

(segment IV. The right 2ranch of the portal vein divides into anterior and posterior

segments approimatel at the point of entr into liver parenchma. The portal veindivides into small veins and venules/ 0hich finall enter hepatic sinusoids. 2undant

vascular intercommunications eist at the sinusoidal level.

The a2sence of portal vein valves has several important implicationsD (1 pressures

o2served in portal vein tri2utaries reflect portal vein pressure/ and therefore/ during surger

for portal hpertension/ portal pressure is convenientl measured in a small mesenteric or

omental veinB (7 the intrahepatic portal vein3s lo0 resistance sustains a large amount of

flo0 despite loss of much kinetic energ to the capillar net0ork of the digestive sstemB

and (@ the speciali4ed intrahepatic architecture accommodates 2oth the high-pressure

hepatic arteries and the portal veins.

Numerous tri2utaries of the portal vein connect outside the liver 0ith the sstemic venous

sstem. ,nder normal circumstances these communications have little phsiologic

significance. 'o0ever/ if portal hpertension develops/ these rudimentar portosstemic

communications develop into large channels 0ith increased collateral flo0. The most

important natural portosstemic anastomoses include (1 the su2mucosal veins of the

proimal stomach and distal esophagus/ 0hich can receive 2lood from the coronar and

short gastric veins to drain into the a4gous veins (high 2lood flo0 through this path0a

produces gastric varices/ esophageal varices/ or 2othB (7 um2ilical and perium2ilical

veins/ recanali4ed from the o2literated um2ilical vein in the ligamentum teres hepaticus/

and 0hich ma cause spectacular phsical findings such as caput medusae or the loudCruveilhier-)aumgarten 2ruitB (@ tri2utaries of the inferior mesenteric vein/ 0hich include

the superior hemorrhoidal veins that communicate 0ith the middle and inferior

hemorrhoidal veins of the sstemic circulation and ma cause large hemorrhoidsB and (

other retroperitoneal communications/ including connections to the renal and adrenal veins.

'epatic rter

The etrahepatic arterial sstem does not parallel the portal channels/ although the

intrahepatic sstem does. #ver =9: of the population have the same anatomic pattern. The

hepatic arter arises from the celiac ais and passes along the upper part of the pancreas

to0ard the liver. $osterior and superior to the duodenum it gives off the gastroduodenalarter. The terms proper or common hepatic arteries refer to the segment proimal or distal

to the origin of the gastroduodenal arter. Note that some anatomic tet2ooks denote those


7/83

terms in reverse (properD distalB commonD proimal to the gastroduodenal arter.

Therefore/ using the entire phrase hepatic arter proimal or distal to the gastroduodenal

arterF is suggested. ;ithin the hepatoduodenal ligament the hepatic arter divides into

right and left 2ranches and su2se5uentl into smaller 2ranches corresponding to the portal

venous sstem/ segmental/ or su2segmental anatom. )ecause of a2undant collaterals/

ligation of the hepatic arter proimal to the gastroduodenal arter fails to damage theliver. "igation of the hepatic arter distal to the gastroduodenal arter can produce hepatic

necrosis and death 2ut also ma not result in serious conse5uences 2ecause of development

of a rich collateral etrinsic 2lood suppl from the celiac ais/ superior mesenteric/ and

inferior phrenic arteries. "igation of the right or left hepatic arter usuall results in

elevated en4me levels 2ut often 0ithout severe clinical manifestations. diffuse

su2capsular arterial pleus ma contri2ute significantl to the hepatic arterial collateral

circulation. #ne angiographic stud has sho0n that rich collaterals can also develop in the

liver3s suspensor ligaments.

The most important variations of the hepatic arterial sstem are a right hepatic arter and acommon hepatic arter arising from a superior mesenteric trunk (replaced hepatic arteries.

#ther anomalies include the left hepatic arter arising from the left gastric arter/ the right

hepatic arter traveling anterior rather than posterior to the 2ile duct/ and the right hepatic

arter traveling posterior to the portal vein. In addition/ the right hepatic arter often has a

curved etrahepatic course/ 0hich ma lead to inadvertent ligation during

cholecstectom. The cstic arter usuall arises from the right hepatic arter 2ut

occasionall arises from the gastroduodenal arter/ the left hepatic arter/ or the common

hepatic arter. !ou2le cstic arteries occasionall occur. ;hen significant hepatic arterial

2ranches arise from the superior mesenteric arter/ the usuall pass to the right side of and

posterior to the portal vein.

'epatic Veins

%ost of the hepatic venous effluent drains into the three ma8or hepatic veinsGright/

middle/ and left. Each has onl a short etrahepatic segment 2efore draining into the

inferior vena cava. In general/ the short etrahepatic segment makes surgical accessi2ilit

difficult/ particularl for control of traumatic 2leeding. The right hepatic vein/ the largest of

the three/ provides the principal drainage for the right lo2e of the liver. The main trunk of

the right hepatic vein follo0s an intersegmental plane 2et0een the &rench segments or the

anterior and posterior segments (merican sstem. Several small veins also normall

drain directl from the right lo2e into the vena cava. The middle hepatic vein lies in thelo2ar (portal fissure draining the medial segment of the left lo2e and a portion of the

anterior segment of the right lo2e. The middle hepatic vein 8oins the left hepatic vein in

69: of dissections. The eact site of 8uncture varies considera2l. The left hepatic vein

provides the principal venous drainage of the left lateral segment. In addition/ several small

veins from the caudate lo2e drain posteriorl directl into the vena cava. fter throm2osis

of the ma8or hepatic veins ()udd-Chiari sndrome/ these small posterior caudate veins

2ecome particularl important.

)iliar SstemThe 2iliar drainage sstem 2egins at the hepatocte level/ 0here portions of the

hepatocte mem2rane form small channels called canaliculi. )ile drains from the canaliculi


8/83

into intrahepatic ducts that follo0 the segmental anatom determined primaril 2 the

vascular suppl. The convergence of canaliculi and proimal ductal sstems is called the

canal of 'ering. The ductal pattern 2ecomes more varia2le distall. The left lo2ar duct

forms in the um2ilical fissure from the union of ducts from segments II/ III/ and IV/ then

passes to the right across the 2ase of segment IV (medial segment of the left lo2e/

topographic 5uadrate lo2e/ and unites 0ith the right lo2ar duct to form the commonhepatic duct. The right hepatic duct drains segments V and VIII and arises usuall from the

8unction of the anterior and posterior segmental (sectoral ducts. The right posterior duct

usuall follo0s almost a hori4ontal course 2efore 8oining 0ith the anterior duct/ 0here it

descends more verticall. The 8unction of the t0o main right 2iliar channels is usuall

found a2ove the right 2ranch of the portal vein.

The shorter etrahepatic right lo2ar duct 8oins the longer left duct at the 2ase of the right

lo2e. The etrahepatic portion of the left lo2ar duct characteristicall is a2out 7 cm. long.

The right and left lo2ar ducts 8oin outside the liver to 2ecome the common hepatic duct/

0hich passes anterior to the portal vein in most persons. The left hepatic duct 8oins theright hepatic duct at a much more anterior and acute angle/ 0hich is an anatomic

consistenc of importance during eploration of the common duct or cholangiograph. The

length of the common hepatic duct varies according to the location of its 8unction 0ith the

cstic duct/ 0here it 2ecomes the common 2ile duct. The hepatic duct confluence varies

considera2l 0ith respect to the union of the right and left main hepatic ducts. The 2iliar

drainage of the topographic caudate lo2e (segment I varies considera2l 2ut enters 2oth

the right and left hepatic duct sstems in a2out 69: of persons. In a2out 1=: of cases/ the

caudate lo2e drains onl into the left hepatic duct sstem/ and in a2out =: it drains onl

into the right hepatic duct.

The upper limit of normal for the diameter of the common 2ile duct is controversial. %ost

references give the upper limit as ? to 6 mm. ecept after cholecstectom/ 0hen the

common 2ile duct ma dilate to 19 to 17 mm. Intrahepatic and etrahepatic ducts usuall

lie anterior to the corresponding portal 2ranches. The etrahepatic 2ile ducts lie 0ithin the

hepatoduodenal ligament. The common hepatic arter ascending to the left of the common

2ile duct gives off the right hepatic arter/ 0hich usuall courses dorsal to the 2ile duct.

"ike the common hepatic duct/ the common 2ile duct varies in length. It passes posterior to

the first part of the duodenum and then courses through the pancreas and the 0all of the

duodenum to form the papilla of Vater on the medial duodenal 0all. The ma8or pancreatic

duct (duct of ;irsung 8oins the common duct in a2out


9/83

2lood suppl of the common 2ile duct arises from the gastroduodenal/ common hepatic/

and right hepatic arteries. pleus formed on the duct provides t0o aial vessels/ the @

o3clock and < o3clock arteries/ named for their positions relative to a cross-section of the

duct.

all2ladder. The gall2ladder/ a pear-shaped/ distensi2le appendage of the etrahepatic

2iliar sstem/ usuall holds @9 to =9 ml. of 2ile. It has a fundus/ 2od/ and neck. Thegall2ladder fills and empties through the cstic duct/ 0hich varies in length and usuall

contains spiral valves of 'eister that regulate 2ile flo0. The valves ma 2e etremel

tortuous/ complicating cannulation during intraoperative cholangiograph. Enlargement of

the neck of the gall2ladder such as from a stone ma form a pouch ('artmann3s pouch.

The triangle 2ounded 2 the cstic duct/ common hepatic duct/ and inferior 2order of the

liver is the triangle of Calot. The gall2ladder receives its 2lood suppl from the cstic

arter/ 0hich originates from the right hepatic arter/ usuall after the latter passes 2eneath

the common hepatic duct. Venous drainage of the gall2ladder enters principall into the

portal vein. The lmphatics drain into cstic duct nodes near the superior aspect of thecstic duct. Venous and lmphatic channels also enter into the liver parenchma.

)iliar Sstem Variants. Variations in the gall2ladder and related anatom are important

during surger/ 2ecause failure to recogni4e variants can produce iatrogenic in8ur . Small

accessor ducts (ducts of "uschka 2et0een the liver and gall2ladder easil escape

detection. "o0 etrahepatic right segmental duct insertions can also 8oin the cstic duct.

The latter in8ur has 2een recogni4ed since the use of laparoscopic cholecstectom.

#ccasionall/ liver parenchma is partiall em2edded in the gall2ladder/ and rarel one

ma encounter a completel intrahepatic gall2ladder. The length of the cstic duct varies/

and it occasionall passes for several centimeters ensheathed 0ith the common hepatic

duct. $assage of the cstic duct posterior and around the common hepatic duct to form a

left-sided 8unction (spiral union occurs in less than =: of persons. The cstic duct ma

also 8oin the right or left hepatic duct or 2e a2sent. *arel/ ma8or hepatic ducts drain

separatel into the gall2ladder.

Common variations in the anatom of the hepatic arter of relevance to this 2iliar

anatom include a 2end in the course of the hepatic arter/ 0hich can mimic the cstic

arter origin/ a short cstic arter takeoff from the right hepatic arter/ dual cstic arteries/

or an arter that courses anterior to the hepatic ductal sstem.

Nerves

The portal and pericapsular regions har2or a distinct/ comple sstem of nerves ofunkno0n clinical importance. n anterior neural pleus consists primaril of smpathetic

fi2ers derived 2ilaterall from ganglia TA to T19 and snapsing in the celiac pleus or of

fi2ers from the right and left vagus and right phrenic nerves. The anterior pleus surrounds

the hepatic arteries. posterior pleus that intercommunicates 0ith the anterior pleus lies

around the portal vein and 2ile ducts. The smpathetic nerves innervate the hepatic arteries.

!istention of the liver capsule or gall2ladder causes pain referred to the right shoulder or

scapula 2 means of the third and fourth cervical nerves. Interruption of the anterior neural

pleus ma have various phsiologic effects/ such as on the composition of secreted 2ile

and the accumulation of fat in the liver. The significance of these findings is not kno0n.

"mphatics


10/83

'epatic lmph forms in the perisinusoidal spaces of !isse and in the clefts of %all to drain

into larger lmphatics in the porta hepatis/ su2se5uentl into the cisterna chli/ and

eventuall into the thoracic duct. "mphatic vessels also lie near the hepatic vein in

lisson3s capsule and around the 2ile ducts. "mphatics also pass through the diaphragm

into the thoracic duct. 'epatic lmph nodes are found in the porta hepatis/ celiac region/

and near the inferior vena cava. Cirrhosis/ veno-occlusive disease/ and glcogenosisproduce lmph vessel dilation. lterations in the permea2ilit of sinusoidal epithelial cells

can alter lmph flo0 and protein content/ an o2servation important in the pathogenesis of

ascites. In8ection of de into the 2ile duct under supraphsiologic pressure reveals

communication 0ith the hepatic lmph vessels/ 2ut the importance of these

communications under phsiologic conditions is unkno0n.

nomalous !evelopment of the "iver

Incomplete or maldevelopment of the hepato2iliar sstem can cause a num2er of

anomalies that are encountered clinicall. Complete a2sence of the liver is rare and not

reported after 2irth. 2sence of the left lo2e has 2een seen. 'epatic transposition has 2eenreported 0ith situs inversus. #ccasionall/ a tongue of liver tissue etends inferiorl from

the right lo2e (*iedel3s lo2eB more fre5uentl encountered in the female/ this condition

usuall causes no smptoms/ although it ma 2e associated 0ith colonic or ploric

o2struction. 'eterotopic liver tissue has 2een seen in the gall2ladder/ pancreas/ adrenals/

spleen/ or 0ithin an omphalocele. &our cases of supradiaphragmatic liver have 2een

reported in the a2sence of a hernia sac.

lthough 2iliar variants are etremel common/ true anomalies are not. )iliar atresia

and choledochocele are the most common serious 2iliar pro2lems seen after 2irth. #ther

a2normalities include congenital a2sence of gall2ladder/ intrahepatic or left-sided

gall2ladder/ multiple gall2ladders/ and a2normalities in the shape of the gall2ladder. The

definition of multiple gall2ladders is determined 2 the presence of more than one cstic

duct. #ther gall2ladder anomalies include septation/ 2ilo2ation/ and duplication of the

cstic duct. #ccasionall the gall2ladder has a long mesenter predisposing to torsion.

$ortal vascular a2normalities include portal agenesis/ congenital portocaval shunt/ a

preduodenal portal vein/ and anomalous pulmonar veins that traverse the diaphragm and

enter the portal sstem.

%icroscopic natom

The cinar ,nit

The smallest functional unit of the liver is the acinus/ a structure first named 2*appaport . In an acinar unit/ the portal venule is accompanied 2 a hepatic arteriole/ a 2ile

ductule/ lmphatics/ and nerves. )lood flo0s from the terminal portal venules into the

sinusoids and comes in contact 0ith hepatoctes in the unit. The 2lood drains into the

terminal hepatic venule. The solutes are removed 2 the hepatoctes/ and their

concentration decreases as the 2lood flo0s to0ard the terminal hepatic venule. The

hepatoctes around the portal venule ais are divided ar2itraril into three 4ones. In 4one 1/

the area immediatel ad8acent to the portal venule/ the sinusoids are smaller in diameter

and more anastomotic than in 4ones 7 and @/ 0hich are farther a0a from the portal

venule. This concept eplains centrilo2ular necrosis that occurs 0ith hpotensionB 4one 1cells are the first to receive 2lood and ogen and the last to eperience hpoia.

%icrocirculation


11/83

The terminal 2ranches of the ma8or inflo0 sstem (the portal vein and the ma8or outflo0

sstem (the hepatic vein do not meet 2ut are regularl interspersed 0ith space 2et0een

them filled 0ith hepatic cell plates and sinusoids. The portal veins and their 2ranches

2ecome progressivel smaller as the penetrate the liver su2stance/ 0hile the terminal

hepatic veins connect 0ith the sinusoidal 2ed/ piercing through closel applied cell plates.

This anatom is clearl a result of the em2rologic development of the liver. &lo0 of portal2lood in the sinusoids is partiall regulated via the peripher of the cell plates.

The 2ranches of the hepatic arter similarl decrease in cali2er as the penetrate the

parenchma/ and their si4e and composition change accordingl. In the terminal 2ranches/

the form a general pleus/ 0hich eventuall terminates in the sinusoids. special

capillar pleus encompasses the 2ile ductsB this net0ork also terminates in the sinusoids.

The peri2iliar pleus appears to pla an important role in ductular 2ile secretion and

a2sorption. Cuffs of smooth muscle surrounding the terminal arterioles help regulate the

flo0 into the sinusoids .

The hepatic sinusoids are A to 1= mm. 0ide/ 2ut the 0idth ma increase to 169 mm. underphsiologic conditions. $ressure 0ithin the sinusoids is onl 7 to @ mm. 'g/ making this an

etremel lo0 resistance sstem. Three anatomic features characteri4e this lo0 resistance

sstemD

1. The sinusoids are lined 2 >upffer3s and endothelial cells/ 0hich overlap loosel and

are not attached to one another. The stellate >upffer3s cell cannot 2e distinguished from

endothelial cells 2 light microscop. 'o0ever/ the former are much larger/ and have

irregular surfaces 0ith folds and microvilli.

7. The endothelial cells are flat and fenestrated/ 0ith openings varing from 9.1 to 7 mm.

in diameter.

@. 'epatocte and mem2rane microvilli pro8ect through the fenestrations of the endothelial

cells and therefore facilitate and maimi4e hepatocte eposure to sinusoidal contents.

The space 2et0een the endothelial lining of the sinusoid and the hepatocte is the

perisinusoidal space of !isse. Important cells located in the perisinusoidal space of !isse

include fi2ro2lasts/ Ito cells (lipoctes/ and neurons. Sinusoids are freel permea2le to

lo0- and high-molecular-0eight su2stances in solution. The sinusoids empt into terminal

hepatic venules/ 0hich in turn empt into hepatic veins of increasing cali2er. The space of

!isse is the primar site for the formation of hepatic lmph.

'epatoctes and Sites of )ile &ormation

'epatoctes represent approimatel ?9: of the cells of the adult human liver and 69: ofthe ctoplasmic mass. These diameters var 2et0een 1@ and @9 mm. The cells have 2oth a

microvillar and smooth surface/ 0ith the microvillar surface lining the perisinusoidal

space. The smooth surface is capa2le of forming microvilli/ particularl during

regeneration and cholestasis. The microvilli of the hepatoctes are not as etensive as the

microvilli of the intestinal epithelial lining/ increasing the surface area 1.?-fold compared

0ith 7-fold for the latter. pproimatel 1=: of the plasma mem2rane encompasses 2ile

canaliculi that remain separated from the pericellular space 2 tight 8unctions and

desmosomes. The main source of canalicular 2ile is across the canalicular mem2rane/

although some paracellular flo0 of small solutes also occurs. The canaliculi measureapproimatel 1 mm. in diameter. The epithelial ductular or ductular lining cells measure

19 mm. in diameter and have a distinct 2asement mem2rane/ in contrast to hepatoctes.


12/83

'epatocte ,ltrastructure

The organi4ation and structure of the hepatocte organelles permit the liver to carr out its

meta2olic functions. %itochondria occup approimatel 16: of the liver cell 2 volume

and participate in oidative phosphorlation and the oidation of fatt acids. "sosomes

cata2oli4e endogenous su2stances as 0ell as some eogenous 0astes. %ultivesicular

2odies contain large amounts of protein derived from plasma. %icrotu2ules and associatedmechanotransducers ma regulate the direction of vesicular transport in the cell. The liver

is uni5ue in that 2oth the smooth and rough endoplasmic reticulum are 0ell developed. s

man as =9 olgi complees occup a hepatocte. The smooth and rough endoplasmic

reticulum and olgi complees are collectivel kno0n as the liver microsomal fraction.

The liver microsomes are kno0n to participate in glcogenolsisB snthesis of cholesterol

and 2ile saltsB esterification of free fatt acids to triglceridesB snthesis of al2umin/

fi2rinogen/ and other proteins destined for eport to the plasmaB and glucuronidation of

2iliru2in/ drugs/ and 2ile salts.

&,NCTI#NThe liver has an etraordinar spectrum of functions. The organ regulates a massive

amount of energB stores/ distri2utes/ and disposes of various nutrientsB and snthesi4es/

transforms/ and meta2oli4es man endogenous su2strates and pollutants. #ver the past =

ears/ ma8or advances have occurred in molecular and cellular 2iolog and

immuno2iolog/ including increased kno0ledge of mechanisms of signal transduction/

gro0th control and cell death/ and mem2rane phsiolog. This section capsuli4es some of

this fundamental 2iolog and practical kno0ledge that influences our understanding of

liver function and surgical disease.

Energ

%ost of the 2od3s meta2olic needs are regulated in some 0a 2 the liver. To accomplish

this/ the liver epends approimatel 79: of the 2od3s energ and consumes 79: to 7=:

of the total utili4ed ogen/ despite constituting onl : to =: of the total 2od 0eight.

The liver architecture seems specific for these demands. The 2lood suppl includes the

portal sstem 2et0een the intestinal and hepatic capillar 2ed/ 0hich helps esta2lish a

remarka2l efficient etrahepatic circulation. The acinar unit permits each cell to 2e 2athed

2 sinusoidal 2lood and at the same time separates a 2iliar compartment 0ithin a portion

of its mem2rane to ensure an ecretor path0a. The hepatocellular organelles in plasma

mem2ranes permit specific functions and/ at the same time/ interrelate 0ith an etracellular

matri/ 0hich facilitates meta2olic echange 2et0een 2lood and hepatoctes.The liver not onl conducts a large num2er of functions 2ut also manufactures a large

num2er of su2stances/ such as plasma proteins/ carnitine/ and creatine/ 0hich service

solel other organs or tissues. The liver collects and transforms such su2strates to meet the

fuel re5uirements of other tissues in response to various meta2olic signals. It is the onl

organ that produces acetoacetate for use 2 muscle/ 2rain/ and kidne 2ut not itself. The

liver also uses little glucose for its o0n re5uirements and epends little of the energ

generated 2 degradation of glcogen. It uses fatt acids that originate from the diet and

fat/ 2ut also easil makes fatt acids as triaclglcerols and phospholipids/ 0hich are

eported. The liver has a special capacit for gluconeogenesis from alanine arising inmuscle 2ut has little capacit for transamination of leucine/ isoleucine/ and valine.


13/83

The energ-related functions of the liver are remarka2l regulated 2 hormones/ other

agonists/ and su2strates coming to and from the liver. No dou2t there are man other

signals that regulate these echanges. The contri2ution of this energ meta2olism to the

2od3s overall acid-2ase 2alance must 2e great/ 2ut surprisingl undiscovered are the

signaling responses so important in this regulation.

&unctional 'eterogeneit and Sinusoidal %em2rane Traffic,nder light microscop/ liver cells look 2asicall the same. 'o0ever/ the cells from

different acinar 4ones 2ehave differentl. In fact/ man of the markers on the cell surfaces

are different depending on the 4one/ or even depth 0ithin a segment. >re2s ccle en4mes

are found highest in concentration in 4one 1/ 0hereas glutamine snthetase is highest in

4one @. The drug-meta2oli4ing $-=9 en4mes are concentrated in 4one @/ particularl after

en4me induction 2 pheno2ar2ital. The hepatoctes in 4one 1/ as epected/ are more

important for 2ile saltHdependent 2ile formation/ 2ecause the are the first to come into

contact 0ith and readil a2sor2 the detergents. In contrast/ the hepatoctes in 4one @ are

more important to 2ile saltHindependent 2ile formation. The differences relate not onl to2lood flo0 2ut also to gene transcription rates.

*eceptor-mediated endoctosis is responsi2le for the transfer of large molecules/ such as

gro0th factors and carrier proteins. ;hen the 2ecome occupied/ the receptors on the

sinusoidal mem2rane cluster into a pit 0hen endoctosis 2egins. Sinusoidal plasma

mem2rane is particularl receptor rich and meta2olicall important. lateral domain/

important in cell-cell interaction/ separates it from the 2ile canaliculus. Endothelial cells

and perisinusoidal cells patrol the sinusoids and have an increasingl recogni4ed diverse

set of functions/ including protection/ immune surveillance/ and regulation of some ma8or

hepatic processes/ including regeneration. $erisinusoidal cells consist of the >upffer3s cells

so important in phagoctosis and antigen presentation/ the fat-storing cells/ or Ito cells/

important in collagen meta2olism and storage of vitamin / and the rare pit cells that have

natural killer cell and neuroendocrine activities. The sinusoidal cells also appear to 2e

important in the production of gro0th-regulating molecules.

)lood &lo0

The liver receives 2lood from the arterial and portal circulationB processes nutrients and

meta2oli4es toins and 0astesB and stores/ transforms/ and distri2utes them to the vascular/

2iliar/ or lmphatic circulations. %ean total hepatic 2lood flo0 has 2een estimated to 2e

199 to 1@9 ml. per kg. per minute. Sevent per cent to A=: of total hepatic 2lood flo0

comes from the portal vein/ 0hile the remainder comes from the hepatic arter. There is areciprocal increase in hepatic arterial flo0 in response to a reduction in the portal flo0/ 2ut

the converse does not occurB portocaval shunt or ligation of the superior mesenteric arter

results in an almost 199: increase in hepatic arterial flo0. The compensation is not

complete/ ho0ever/ so total hepatic flo0 does not return to normal. *efle neural control

and autoregulation appears to 2e an important regulator factor for hepatic arterial flo0 2ut

not for portal venous flo0. To a large etent/ portal venous flo0 into the liver is regulated

2 etrahepatic factors such as the rate of flo0 from the intestines and spleen. &ood/ 2ile

salts/ secretin/ cholecstokinin/ pentagastrin/ epinephrine/ vasoactive intestinal peptide/

glucagon/ and isoproterenol all increase portal 2lood flo0. lthough it is conceiva2le thatflo0 0ould increase 2ased on nutritional status/ 2ecause of hepatic arterial flo0 regulation

the total flo0 does not var 0ith meta2olic state of the organism.


14/83

)oth intrinsic and etrinsic factors appear to 2e important in controlling the varia2le

arterial 2lood flo0. Intrinsic flo0 regulation occurs through arterial autoregulation 2ased

on the local concentration of adenosine surrounding the hepatic arteriole and portal venule.

denosine is a potent arteriolar dilatorB an increase in portal flo0 0ashes out perivascular

adenosine and results in constriction of the hepatic arteriole/ there2 maintaining a constant

level of hepatic 2lood flo0. "ess is kno0n a2out the etrinsic control mechanisms.$ossi2le humoral regulators of etrinsic regulation include gastrin/ glucagon/ secretin/ and

2ile salts. The hepatic arter is also densel innervated 2 smpathetic nerves and

constricts in response to alpha-adrenergic receptor stimulation. 'epatic arterial flo0 and

pressures reflect the sstemic sstem.

$ortal 2lood flo0 appears to 2e controlled 2 resistance across a distinct hepatic venousH

like 4one. In normal liver there is no resistance attri2uta2le to either the portal venule or

sinusoid. In eperimental models/ hepatic venous sphincters appear to contract in response

to histamine/ norepinephrine/ and angiotensin. $ortal venous pressures range from A to 19

mm. 'g/ 0hile sinusoidal pressures are 7 to mm. 'g a2ove the pressure in the inferiorvena cava.

Intrinsic liver flo0 is to a degree compara2le to a sponge/ 2ut 0ith various methods of

regulation. The microvasculature is regulated 2 a series of sinusoidal inlet and outlet

sphincters. 'epatic inflo0 increases 0ith epiration and decreases 0ith inspiration/ 0hich

is opposite to the phasic flo0 in the vena cava. !uring vigorous eercise/ total hepatic

2lood flo0 is decreased 2ecause of shunting of 2lood to muscle and the 2rain. The liver

serves as a phsiologic reservoir of 2loodD 7=: to @9: of its volume is composed of

2lood/ and during acute 2lood losses/ @99 ml. or more can 2e released into the sstemic

circulation 0ithout adverse effects on liver function. Conversel/ in the face of right-sided

heart failure/ up to 1999 ml. of 2lood can 2e stored in the liver 0ithout affecting liver

function.

)ile &ormation

)ile secretion is an active process/ relativel independent of total liver 2lood flo0/ ecept

in conditions of shock. )ile is formed at t0o sitesD (1 the canalicular mem2rane of the

hepatocte and (7 the 2ile ductules or ducts . Total unstimulated 2ile flo0 in a A9-kg. man

has 2een estimated to 2e 9.1 to 9.@ ml. per minute. Eight percent of the total dail

production of 2ile (1=99 ml. is secreted 2 hepatoctes and 79: is secreted 2 the 2ile

duct epithelial cells. The principal organic compounds in 2ile are the con8ugated 2ile acids/

cholesterol/ phospholipids/ and protein. )ecause of the ecellent correlation 2et0een 2ileacid output and 2ile flo0/ the term 2ile acidHdependent flo0 is used to descri2e this

fraction of 2ile formationD 2ile flo0 is linearl related to 2ile acid output. Secretion of

cholesterol and phospholipid is closel linked to the output of 2ile acids/ ecept under

certain conditions such as insulin or glucagon stimulation.

The 2ile canaliculus is a long narro0 channel that 2egins as a space of approimatel 1

mm. in diameter/ 2ounded 2 t0o or three hepatocte canalicular mem2ranes. It has no

0all of its o0n/ 2ut the mem2rane has numerous microvilli. Canalicular flo0 ma 2e

generated in near a2sence of 2ile acids or during sta2ili4ed 2ile acidHdependent flo0/ and

this is termed the 2ile acidHindependent canalicular fraction. 2undant evidence eistsno0/ suggesting that this independent fraction of 2ile ma actuall 2e controlled 2 hepatic

2ile production.


15/83

s 2ile passes through the 2iliar ductules or ducts it is modified 2 secretion or a2sorption

of epithelial cells. The highest cells in the 2iliar ductules have functions and architecture

in common 0ith 2oth hepatoctes and ductular cells and so are called cholangioctes.

Secretion from 2iliar epithelial cells (canalicular 2ile appears to 2e dependent on chloride

channel stimulation. The 2est characteri4ed hormone stimulator is secretin. Etracellular

signaling molecules ma control ion channels on the apical surface of the 2ile ductepithelial cells. The presence of such signals suggests an origin upstream of the canalicular

mem2rane. These molecules ma provide alternate methods to stimulate canalicular 2ile

flo0 in conditions such as 2ile stasis or secretin-associated chloride channel defects (such

as cstic fi2rosis. Cholangioctes contain receptors for epidermal gro0th factor/ secretin/

and somatostatin.

The onl kno0n function of the gall2ladder is to concentrate and store 2ile during fasting.

pproimatel


16/83

per da/ and this 5uantit is replaced 0ith ne0l snthesi4ed 2ile acids. Therefore/ 79 to 9

times more 2ile acid than is normall snthesi4ed is delivered into the intestine/

underscoring the importance of this circulation. ,nder normal circumstances/ serum 2ile

acid levels are lo0 (= mmol. 2ecause of the a of 2ile acids so the remain ioni4ed in the intestinal lumen and are not passivela2sor2ed through nonionic diffusion. Con8ugated 2ile acids also form micelles/ 0hich more

effectivel facilitate lipid digestion and a2sorption from the small intestine. Various

intestinal pro2lems such as regional enteritis/ ileal resection/ Jollinger-Ellison sndrome/

radiation enteritis/ and 2lind loop sndrome ma 2e associated 0ith deficient 2ile acid

a2sorption/ 0hich leads to diarrhea/ steatorrhea/ or vitamin ) 17 deficienc. decreased

2ile acid pool ma also predispose to the formation of gallstones. In 2lood/ 2ile salts are

tightl 2ound to 2oth serum al2umin and lipoproteins/ particularl high-densit lipoprotein.

'epatic uptake is carrier mediated and follo0s %ichaelis-%enten kinetics.

)iliru2in %eta2olism

)iliru2in/ a 2reakdo0n product of heme/ is ecreted almost entirel in the 2ile. ;ith

hepatocellular disease or etrahepatic 2iliar o2struction/ free 2iliru2in ma accumulate in

2lood and tissues. pproimatel A=: of 2iliru2in is derived from senescent red 2lood

cells. )iliru2in circulates 2ound to al2umin/ 0hich protects tissue from its toicit. It is

rapidl removed from the plasma 2 the liver through a carrier-mediated transport sstem.

In the hepatocte/ 2iliru2in is 2ound to other proteins (+ and J/ 0hich pro2a2l have a

role in transport. It is con8ugated 0ith glucuronide and secreted in 2ile. Con8ugated

2iliru2in ma form a covalent 2ond 0ith al2uminB this is called delta 2iliru2in. The

implications of delta 2iliru2in are still 2eing investigated.

!isorders of 2iliru2in meta2olism leading to predominantl uncon8ugatedhper2iliru2inemia include neonatal hper2iliru2inemia/ Crigler-Na88ar Tpe I (0hich

usuall leads to kernicterus and death/ the more 2enign Crigler-Na88ar Tpe II/ and

il2ert3s sndrome. !isorders characteri4ed 2 predominantl con8ugated

hper2iliru2inemia include !u2in-Kohnson sndrome/ *otor3s sndrome/ and recurrent

intrahepatic cholestasisB patients 0ith these disorders usuall have a 2enign course.

In the intestine/ 2iliru2in is reduced 2 2acteria to meso2iliru2inogen and sterco2ilinogen/

collectivel termed uro2ilinogen. These are 2oth ecreted in the stool. fraction of

uro2ilinogen is oidi4ed to uro2ilin/ 0hich is 2ro0n pigment and gives stool its normal

color. $art of uro2ilinogen is resor2ed in the intestine and ecreted in the urine. ;ithcomplete 2iliar o2struction/ uro2ilinogen cannot form and/ therefore/ 0ill not appear in

the urine.


17/83

Car2ohdrate %eta2olism

The liver has a central role in energ meta2olismD it helps provide a continuous source of

glucose for the central nervous sstem and red 2lood cells. !uring the fed state/ results of

intestinal car2ohdrate digestion (glucoseD 69:B and galactose and fructoseD 79: are

delivered to the liver. The latter t0o are rapidl converted to glucose. lucose a2sor2ed 2

the hepatocte is converted directl to glcogen for storage up to a maimum of ?= gm. ofglcogen per kg. of liver mass. Ecess glucose is converted to fat. lcogen is also

produced 2 muscle/ 2ut this is not availa2le for use 2 an other tissues. !uring the

fasting state/ this glcogen is the primar source of glucose. 'o0ever/ after 6 hours of

fasting/ liver glcogen is ehausted/ and proteins mo2ili4ed primaril from muscle/ mainl

alanine/ are converted 2 the liver to glucose.

"actate produced 2 anaero2ic meta2olism is meta2oli4ed onl in the liver. #rdinaril it is

converted to pruvate and su2se5uentl 2ack to glucose. This shuttling of glucose and

lactate 2et0een liver and peripheral tissue is carried out in the Cori ccle. The 2rain does

not participate in this ccle/ and a continuous source of glucose for the 2rain must come atthe epense of muscle proteins.

In liver disease/ the meta2olism of glucose is often deranged. &re5uentl/ in patients 0ith

cirrhosis/ the portosstemic shunting causes decreased eposure of portal 2lood to the

hepatoctes/ producing an a2normal result of the oral glucose tolerance test. 'poglcemia

is rare in chronic liver disease/ since the snthetic capacit of hepatoctes is preserved until

late in the disorder. In fulminant hepatic failure/ ho0ever/ there is etensive loss of

hepatocte mass and function/ and hpoglcemia supervenes as gluconeogenesis fails.

"ipid %eta2olism

There are three sources of free fatt acid availa2le to the liverD fats a2sor2ed from the gut/

fat li2erated from adipoctes in response to lipolsis/ and fatt acids snthesi4ed from

car2ohdrates and amino acids. These fatt acids are esterified 0ith glcerol to form

triglceride. The eport of triglcerides is dependent on the snthesis of ver lo0 densit

lipoproteins. In cases of ecess suppl of fatt acid/ there is lipid accumulation in the liver

2ecause there is an im2alance of triglceride relative to ver lo0 densit lipoproteins. This

is seen in o2esit/ corticosteroid use/ pregnanc/ dia2etes/ and total parenteral nutrition.

Simple protein malnutrition or protein-calorie im2alance ma also result in fatt change of

liver/ 2ased on decreased eport of triglcerides/ 2ecause of limited suppl of precursors

for hepatic snthesis of lipoproteins.

The fatt infiltration of alcohol a2use is the result of several a2normalitiesD (1 alcohol is asource of calories/ 0hich are converted to acetl-coen4me / 0hich is a su2strate for fat

snthesisB (7 the reduced form of nicotinamide-adenine dinucleotide produced in the

meta2olism of alcohol inhi2its fatt acid oidation and shifts meta2olism to0ard

triglceride snthesis and esterificationB and (@ chronic alcoholism ma/ 2ecause of

malnutrition/ inhi2it snthesis of ver lo0 densit lipoproteins.

The liver also has a central role in cholesterol meta2olism. It is the most active site of

cholesterol and 2ile salt snthesis. In mammals/


18/83

lo0 densit lipoproteins/ and high densit lipoproteins. The ma8or carriers of cholesterol

are lo0 densit lipoproteins. )ile salt snthesis is the ma8or cata2olic path0a of

cholesterol in liver/ and A-alpha-hdrolase is the rate-limiting en4me for the conversion

of cholesterol to 2ile acids. The other important route of cholesterol elimination is direct

secretion into the 2ile.

$rotein %eta2olism'epatic protein snthesis and cata2olism are vitall important. t least 1A of the ma8or

human plasma proteins are snthesi4ed and secreted 2 the liver. The liver is the onl

organ that produces serum al2umin and alpha-glo2ulin/ and it snthesi4es most of the urea

in the 2od. $roduction of various serum proteins is an important inde of liver function.

l2umin is the most a2undant serum protein/ its snthesis accounting for 11: to 1=: of

total hepatic snthesis. Snthesis of al2umin is influenced 2 nutritional status/ throine/

insulin/ glucagon/ cortisol/ and ctokines produced in the sstemic inflammator response.

!ramatic changes in 2oth tpe and amount of plasma protein produced 2 the liver take

place in sstemic inflammator states. The acute-phase reactants produced 2 the liver inresponse to interleukin-? increase in a sudden transient rise in production of several

proteins. These include C-reactive protein/ serum amloid / and fi2rinogen. l2umin

snthesis decreases. The acute-phase proteins have a 0ide range of 2iologic activities/

including inhi2ition of proteases/ 2lood clotting/ opsoni4ation of 2acteria and de2ris/

modulation of the immune response/ and 2inding of heav metals. In general/ it is thought

that the acute-phase reactants locali4e and limit the tissue damage 0hile enhancing

micro2ial clearance.

Vitamin %eta2olism

The liver has man important roles in the uptake/ storage/ and mo2ili4ation of vitamins.

%ost important are the fat-solu2le vitamins / !/ E/ and >. The a2sorption of these is

dependent on 2ile salts. The vitamins appear in the thoracic duct 7 to ? hours after oral

administration. Vitamin is eclusivel stored in the liver/ and ecessive ingestion of

vitamin ma 2e associated 0ith significant liver in8ur. role for the storage of vitamin

in Ito cells has 2een suggested. The initial step in vitamin ! activation occurs in the

liver/ 0here vitamin ! @ is converted to 7=-hdrocholecalciferol.

#f particular surgical significance 0as the discover of vitamin >. This vitamin is essential

for the gamma-car2olation of the vitamin >Hdependent coagulation factors II/ VII/ IL/

and L. These factors are inactive 0ithout gamma car2olation. In 1


19/83

formation of vitamin >Hdependent factors 2 reducing the amount of vitamin > availa2le

to participate in gamma car2olation of these factors. Clinicall/ 0arfarin is follo0ed 2

o2serving the prothrom2in time. *eversal of the effect of 0arfarin occurs 2 parenteral

administration of vitamin > or coagulation factors.

Classicall/ there are t0o path0as for fi2rin formation (intrinsic and etrinsicB

phsiologicall/ it is more likel that the t0o act in concert. The etrinsic path0a causeslarge amounts of clot to 2e formed in seconds and is limited onl 2 the amount of tissue

throm2oplastin released. The intrinsic path0a re5uires several minutes to form a clot and

can 2e 2locked 2 a num2er of inhi2itors. In clinical practice/ the etrinsic path0a is

monitored 2 measuring the prothrom2in time/ 0hereas the intrinsic path0a is monitored

2 measuring the partial throm2oplastin time or accelerated partial throm2oplastin time.

&actor VII has the shortest half-life (= to A hours/ and in patients 0ith hepatic dsfunction

the snthetic a2ilit of the liver ma 2e assessed 2 monitoring the prothrom2in time/

2ecause this test is dependent on ade5uate amounts of functional factor VII.

%eta2olism of !rugs and Toins!rug and toin meta2olism is primaril a hepatic function. The range of meta2olic

transformations that foreign compounds undergo is convenientl categori4ed into t0o

2road headingsD (1 the phase I reactions of oidation/ reduction/ and hdrolsis and (7 the

phase II reactions/ in 0hich a compound is com2ined 0ith an endogenous molecule to

form a con8ugate. #idative reactions represent most of the phase I 2iotransformations in

0hat has come to 2e kno0n as the ctochrome $-=9 sstem.

*egeneration

Clinicall/ the regenerative capacit of the liver is 0ell kno0n and tpicall triggered 2

partial hepatectom. !uring the midlife of humans/ the liver 0ill regenerate to a volume of

7= M 1.7 ml. per kg. 'o0ever/ the eact time course for the regenerative phase in humans is

lacking. Van Thiel and associates have previousl presented clinical data on t0o patients

receiving livers from donors an average of 19 kg. smaller than the recipients/ 0hich

resulted in livers 7


20/83

functional liver mass. &urther investigations are necessar to characteri4e more full the

regenerative response of the liver.

&uture !evelopments

num2er of areas of active research are likel to develop ne0 concepts 0ith respect to

disease and therap. dvances are likel in the follo0ing fieldsD (1 characteri4ation of

liver stem cells/ (7 methods of molecular modification of the genome/ (@ hepatoctetransplantation or replacement/ and ( apoptosis. Studies of liver development have sho0n

that committed endodermal cells form hepato2lasts that have dual lineage progenitor

capacit and give rise to mature hepatoctes/ intrahepatic 2ile ducts/ and portions of the

etrahepatic ducts. Certain chemicals induce the proliferation of oval cells/ 0hich ma pla

some role in carcinogenesis. Considera2le research is ongoing 0ith respect to permissive

conditions for hepatocte engraftment and survival. Transplantation of hepatoctes in

ectopic sites has led to some enthusiasm 0ith respect to their use in acute liver failure and

also in methods of altering the genes of cells for 2etter integration into the host. ene

therap seems to have a great deal of potential applica2ilit to the liver. This research isdivided into t0o general strategies/ somatic cell and germ cell therap (i.e./ introduction of

foreign genes into nongerm cell versus germ cell lines. The strategies can 2e further

su2divided into gene replacement or augmentation strategies/ e vivo and in vivo. Some

progress has 2een reported 2 using viral vectors or other carriers/ and 2 targeted deliver

of polnucleotides to inhi2it gene epression. poptosis/ or !N-encoded cell death/

appears to pla an important role in the cessation of liver regeneration. Earl validation of

this concept in the liver has led to a great flurr of research relating apoptosis to 2enign or

malignant conditions.

ssessment of "iver &unction

lthough there is no magic test/ a num2er of methods are useful in the diagnostic

evaluation of the patient 0ith potential liver disease. In this section are mentioned onl

some routine tests of liver function and several 5uantitative estimates of liver function.

*outine Tests

*outine tests of liver function include the liver transaminases/ 0hich are named either 2

the products of the reaction (i.e./ serum glutamic oaloacetic transaminase OS#TP and

serum glutamic pruvic transaminase OS$TP or 2 the amino group donor (i.e./ aspartate

transaminase OSTP or alanine transaminase O"TPB alkaline phosphatase ("$B gamma-

glutaml transpeptidase (TB leucine aminopeptidase ("$B =3-nucleotidaseB serum

al2umin and transferrinB and serum lipids and lipoproteins."iver Transaminases. Increased liver transaminase levels in liver disease reflect leakage

from in8ured liver cells. The degree of elevation of the transaminases generall reflects the

severit of hepatic necrosis/ ecept in the important setting of alcoholic hepatitis/ 0hen

levels seldom eceed 799 to @99 I.,. per liter.

lkaline $hosphatase ctivit. ctivit of "$ is detected in man tissues/ including the

liver/ 2ile ducts/ intestines/ 2one/ kidnes/ placenta/ or 0hite 2lood cells. The serum "$

level is also elevated in a num2er of conditions not associated 0ith hepato2iliar disease/

such as pregnanc/ normal gro0th/ 2one tumors/ and liver tumors (the *egan isoen4me.

The reason for "$ elevation is apparent in most cases. ;hen the reason is not apparent/several methods/ such as electrophoresis and relative heat sta2ilit/ differentiate the

hepato2iliar en4me from other isoen4mes. The most availa2le solution in the clinical


21/83

setting is to order a =3-nucleotidase/ "$/ or T activit measurement. These generall

parallel "$ levels in hepato2iliar disease. Increased serum hepato2iliar "$ activit

indicates 2ile duct o2struction/ parenchmal disease/ infiltrative lesions of the liver/ or

repair after hepatocte in8ur. Increased "$ activit reflects 2oth increased en4me

snthesis and altered 2iliar ecretion or leakage from damaged cells. The highest levels of

"$ occur/ in general/ 0ith etrahepatic 2ile duct o2struction/ follo0ed 2 intrahepaticcholestasis and then neoplasms of the liver. The degree of "$ elevation is a predictor of

the degree of liver involvement or metastatic disease.

#ther En4mes. "$ is a u2i5uitous cellular peptidase/ and =3-nucleotidase is a plasma

mem2rane en4me. T is present in man tissues/ and its elevation suggests

hepato2iliar disease/ mocardial infarction/ or pancreatic or neuromuscular disease. T

also monitors the degree of ingestion of alcohol.

l2umin. l2umin is a useful clinical marker of snthetic function in chronic hepatic

insufficienc. It is snthesi4ed onl in the liver/ and its level in the 2lood is determined 2

liver function/ nutritional state/ throid hormone/ or adrenal corticosteroids. The normalrate of al2umin snthesis is 119 to 799 mg. per kg. per da. The eact mechanisms

involved in al2umin meta2olism in the health state are not clear. l2umin loss is

augmented in certain disease states/ such as 2urns/ sepsis/ nephrotic sndrome/ and protein-

losing enteropathies. ;hen other mechanisms of al2umin loss are ecluded/ the serum

al2umin level is an accurate marker of liver failure or altered hepatic function.

,nfortunatel/ 2ecause of its long half-life/ al2umin measures 8ust chronic and not acute

liver failure.

Transferrin. lso snthesi4ed in the liver/ transferrin has a much shorter half-life than

al2umin. Changes in transferrin levels reflect more acute changes in liver function than do

changes in al2umin levels. "ipid and lipoprotein electrophoreses also change in acute or

chronic liver disease/ o0ing to a2normal or altered snthesis. %uch 0ork has gone into

investigating these patterns/ 2ut their measurement has not et proved particularl useful

clinicall.

Specific Tests. Specific tests of liver disease include screening tests for hepatitis and for

other 2enign chronic liver disease. Such tests include antimitochondrial (primar 2iliar

cirrhosis/ smooth muscle (sclerosing cholangitis/ antinuclear anti2od/ alpha 1-antitrpsin

(antitrpsin deficienc/ 2lood alcohol/ plasma ceruloplasmin/ or amlase levels. Specific

markers for neoplasms include alpha-fetoprotein and carcinoem2ronic antigen levels.

Infectious serologic markers include ctomegalovirus/ Epstein-)arr virus anti2odies/leptospiral agglutination/ fasciola/ ame2a/ hdatid complement fiation tests/ and the

;asserman reaction.

Quantitative ssessment

)romsulphalein and Indocanine reen. These des are removed from the circulation 2

the liver. Such intravenous tests have 2een used to assess liver dsfunction in the a2sence

of 8aundice. Each is a measure of 2iliar ecretion and is a more specific 5uantitative test

than an of the routine tests of liver function or cholestasis. 'o0ever/ neither has particular

clinical utilit/ and 2romsulphalein has a long histor of 2eing put on and taken off the

commercial market.alactose Elimination Capacit. This test reflects hepatocellular function 2ut re5uires

multiple determinations over a 7-hour period. alactose is safe and in8ected intravenousl


22/83

at a dose that saturates the en4me sstem responsi2le for its elimination. The preliminar

step is the initial phosphorlation 2 galactokinase.

minoprine )reath Test. minoprine as 0ell as caffeine have 2een used as 2reath test

su2stances that measure the efficienc of the ctochrome $-=9 (microsomal sstem

0here the are meta2oli4ed. minoprine is la2eled 0ith car2on-1 and given 2 mouth.

Car2on dioide samples la2eled 0ith car2on-1 are collected at intervals over 7 hours. Thistest reflects the residual functional microsomal mass and/ thus/ via2le hepatic tissue. It has

more value in assessing prognosis than for screening. Serial salivar caffeine clearance is a

similar measure. ntiprine clearance can also 2e measured/ 2ut the test re5uires over @9

hours.

"idocaine %eta2olite &ormation (%EL Test. "idocaine similarl is meta2oli4ed 2

oidative N-demethlation 2 the ctochrome $-=9 sstem. %onoethlglcinelidide

(%EL is formed correlating 0ith lidocaine clearance. Clearance 1= minutes after

in8ection gives a 5uantitative assessment of liver function/ 0hich ma correlate 0ith graft

survival 2efore liver transplantation.Tests of Coagulation. The prothrom2in time is in general a sensitive marker of the severit

of liver failure. $rolongation indicates deficienc not onl of the throm2in comple 2ut

also of factors LI and LII. Estimation of individual clotting factors is rarel re5uired.

'o0ever/ some evidence suggests that a factor V concentration of less than 19: on

admission in acetaminophen-induced acute liver failure predicts a poor outcome. The ratio

of factor VIII to factor V ma also 2e valua2le. $rognostic significance of several other

clotting factors relating to various kinds of fulminant failure is receiving intensive scrutin.


23/83

II. $+#ENIC N! %E)IC "IVE* )SCESS

$+#ENIC N! %E)IC "IVE* )SCESS"iver a2scess remains a formida2le diagnostic and therapeutic pro2lem/ 2ut significant

strides in management have occurred over the past t0o decades. Changing etiologies of

liver a2scess reflect 2oth improvements in health care and increased recognition of the

condition in sicker/ often immunocompromised patients. $ogenic (2acterial and ame2ic

a2scesses share man clinical features and are therefore discussed together. The pogenic

tpe is much more common in most sections of the ,nited StatesB et ame2ic a2scess is

endemic in man areas of the 0orld and re5uires clinical suspicion for correct diagnosis.

&ungi/ ctomegaloviruses/ and other organisms also cause liver a2scess/ predominantl in

the immunocompromised host/ 2ut are less common and usuall cause more diffusehepatic disease. Echinococcosis generall has a different clinical presentation from

pogenic or ame2ic a2scess/ unless there is secondar 2acterial involvement.

"iver a2scess has 2een recogni4ed since 'ippocrates (circa 99 ).C./ 0ho speculated that

prognosis is related to the tpe of fluid 0ithin the lesion. 71 In the earl nineteenth centur/

)right ? suggested that ame2ae might contri2ute to the formation of hepatic a2scess/ and

>och/ in 166@/ descri2ed ame2ae in the 0all of a hepatic a2scess. &it4 19 and !ieulafo

Date post:	03-Jun-2018
Category:	Documents
Upload:	mohammad-hafiz
View:	235 times
Download:	0 times

surgical diseases of liver

Documents