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Structure of the Liver and Biliary System

Structure of the Liver and Biliary System

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Published by Marwan M.

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Published by: Marwan M. on Jun 30, 2010
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05/16/2012

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STRUCTURE OF THE LIVER AND BILIARY SYSTEM
The liver 
The liver is the
largest internal
organ in the body
(1.2-1.5 kg)
and is situated in the righthypochondrium. Functionally, it is divided into right and left lobes by the
middle hepatic vein
.
 
The right lobe is
larger 
and contains the caudate and quadrate lobes. The liver is further subdivided into a total of eight segments by
divisions
of the right, middle and left hepatic
veins
. Each segment receives its own portal pedicle, permitting individual segment resectionat surgery.The blood supply to the liver constitutes 25% of the
resting cardiac output
and is via twomain vessels:
y
 
The hepatic artery 
,
which is a branch of the
coeliac axis
, supplies
25%
of the totalblood flow.
Autoregulation
ensures a constant total liver blood flow.
y
 
The portal vein
drains most of the GIT and the spleen. It supplies
7
5%
of the bloodflow.
The normal portal pressure is 5-8 mmHg
;
flow increases after meals
.Both vessels enter the liver via the hilum (porta hepatis). The blood from these vessels isdistributed to the segments and passes into the
sinusoids
via the portal tracts.Blood leaves
the sinusoids
, entering branches of 
the hepatic vein
which join into three mainbranches before entering
the inferior vena cava
.
The
caudate lobe
is an autonomous segment
as it receives an independent blood supplyfrom the portal vein and hepatic artery, and its hepatic vein drains
directly
into the inferior 
 
vena cava.
Lymph
,
formed mainly in the perisinusoidal space, is collected in lymphatics which arepresent in the
portal tracts
. Eventually drain into
the hepatic ducts
.
The acinus
is the functional unit of the liver. This consists of parenchyma supplied by thesmallest portal tracts containing
y
Portal vein radicles.
y
Hepatic arterioles.
y
Bile ductules. The hepatocytes near this triad
(zone 1)
are well supplied withoxygenated blood and are more resistant to damage than the cells nearer the
terminal hepatic (central) veins (zone 3).
 The
sinusoids
 
lack a basement membrane
and are loosely surrounded by specialist
fenestrated endothelial cells and Kupffer cells (phagocytic cells).
Sinusoids are
separated
by plates of liver cells
(hepatocytes).
The subendothelial space that lies betweenthe sinusoids and hepatocytes is
the space of Disse
,
which contains a matrix of basementmembrane constituents and stellate cells.
tellate cells
store retinoids in their resting state and contain the intermediate filament,desmin. When activated
(to myofibroblasts)
produce extracellular matrix components,including collagen and they are contractile and probably regulate sinusoidal blood flow.Endothelin and nitric oxide play a major role in modulating stellate cell contractility.
The biliary system
B
ile canaliculi
form a network between the hepatocytes. These join to form thin
bileductules
near the portal tract, which in turn enter 
the bile ducts
in the portal tracts. Thesethen combine to form
the right and left hepatic ducts
that leave each liver lobe. The hepaticducts join at the porta hepatis to form
the common hepatic duct
.
The cystic duct
connectsthe gall bladder to the
lower end
of the common hepatic duct. The gall bladder lies under theright lobe of the liver and stores and concentrates hepatic bile; it has a capacity of approximately
50 mL
.
The common bile duct
is formed by the combination of the cystic andhepatic ducts and is
approximately 8 mm in diameter 
, narrowing at its distal end to pass
 
into the duodenum.
The common bile duct and pancreatic duct open into the secondpart of the duodenum
 
through a common channel at the ampulla of Vater 
. The lower end of the common bile duct contains
the muscular sphincter of Oddi
, which contractsrhythmically and
prevents bile from entering the duodenum in the fasting state
.
rotein metabolism
The liver is the principal site of synthesis of all circulating proteins apart from
-globulins
,which are produced in
the reticuloendothelial system
. The liver receives amino acids fromthe intestine and muscles and, by controlling the rate of gluconeogenesis and transamination,regulates levels in the plasma.
Plasma contains 60-80 g/L of protein
, mainly in the form of 
albumin
,
globulin
and
fibrinogen
.
Albumin
has a half-life of 16-24
days
, and 10-12 g are synthesized daily. Its mainfunctions are1. to maintain the intravascular oncotic (colloid osmotic) pressure.2. to transport water-insoluble substances. Reduced synthesis over prolonged periodsproduces hypoalbuminaemia and is seen in CLD and malnutrition,
hyper catabolicstates
(e.g. trauma with sepsis) and in diseases where there is an excessive loss(e.g. nephrotic syndrome, protein-losing enteropathy).Transport or carrier proteins such as transferrin and caeruloplasmin, acute-phase and other proteins (e.g. 
1
-antitrypsin and -fetoprotein) are also produced in the liver.The liver also synthesizes all factors involved in coagulation (apart from one-third of factor VIII) and the complement system. The liver stores
large amounts
of vitamins, particularly A,D and B
12
, and
lesser amounts
of others (vitamin K and folate), and also minerals - iron inferritin and haemosiderin and copper.Degradation (nitrogen excretion) Amino acids are degraded by transamination and oxidative deamination to produce
ammonia
 
urea
and excreted by the kidneys. This is a major pathway for the elimination of nitrogenous waste. Failure of this process occurs in severe liver disease.
arbohydrate metabolismThe liver 
stores approximately 80 g of glycogen
,
major functions are:
y
Glucose homeostasis
y
The maintenance of the blood sugar.
I
n the immediate fasting state
,
blood glucose is maintained either by:
 
 
y
Glycogenolysis (glucose released from the breakdown of glycogen)
y
or by gluconeogenesis (newly synthesized glucose).
S
ources for gluconeogenesis
 are lactate, pyruvate, amino acids from muscles (mainly alanine and glutamine) andglycerol from lipolysis of fat stores.
I
n prolonged starvation
, ketone bodies and fatty
 
acids are used as alternative sources of fuel as the body tissues adapt to a lower glucose requirement.
L
ipid metabolism
 Are transported in the plasma as lipoproteins.
The liver synthesizes VLDLs and HDLs.
 HDLs are the substrate for lecithin-cholesterol acyltransferase (LCAT), which catalyses theconversion of free cholesterol to cholesterol ester (see below).
Hepatic lipase
removestriglyceride from IDLs to produce ILDLs) which are degraded by the liver.TGs are mainly of 
dietary origin
but are also formed in the liver from circulating (FFAs) andglycerol and incorporated into VLDLs. Oxidation or de novo synthesis of FFA occurs in theliver, depending on the availability of dietary fat.Cholesterol may be of dietary origin but
most is synthesized from acetyl-CoA
mainly in theliver, intestine, adrenal cortex and skin. It occurs either as free cholesterol or is esterified withfatty acids; this reaction is catalysed by LCAT which reduced in severe liver disease,
 
increasing the ratio of free cholesterol to ester, which alters membrane structures. One resultof this is the red cell abnormalities (e.g. target cells) seen in chronic liver disease.Phospholipids (e.g. lecithin) are synthesized in the liver.
ormation of bile
Bile secretion and bile acid metabolism
B
ile consists of 
water, electrolytes, bile acids, cholesterol, phospholipids and conjugatedbilirubin. Two processes are involved in bile secretion -
a
bile salt-dependent 
and a
bilesalt-independent 
process - each contributing about 230 mL/ day. The remainder of the bile(about 150 mL daily) is produced by the
epithelial cells
of the
bile ductules
.Bile formation requires
firstly
the uptake of bile acids and other organic and inorganic ionsacross the basolateral (sinusoidal) membranes. This process is driven by Na
+
/K
+
-ATPase inthe basolateral membrane. .Bile acids are also synthesized in hepatocytes from cholesterol. The
rate-limiting step
intheir production is that catalysed mainly by cholesterol-7-hydroxylase and the P450enzymes (CYP7A1 and CYP8B1).
y
Secretion of a bicarbonate-rich solution is stimulated mainly by secretin and isinhibited by somatostatin.The bile acids are excreted into the bile and then pass via the common bile duct into theduodenum. The two primary bile acids - cholic acid and chenodeoxycholic acid areconjugated with glycine or taurine (in a ratio of 3: 1 in humans) and this process increasestheir solubility. Intestinal bacteria convert these acids into secondary bile acids, deoxycholicand lithocholic acid.
The average total bile flow is approximately 600 mL per day
.
I
n the fasted state
 
half 
of the bile flows directly into the duodenum
and half 
is diverted into the gall bladder. Themucosa of the gall bladder absorbs 80-90% of the water and electrolytes, but is impermeableto bile acids and cholesterol.
Following a meal
,
cholecystokinin is secreted by the I cells of 
 
the duodenal mucosa and stimulates contraction of the gall bladder and relaxation of thesphincter of Oddi, so that bile enters the duodenum. An adequate bile flow is dependent onbile salts being returned to the liver by the enterohepatic circulation.
B
ile acids act as detergents
; their main function is lipid solubilization. Bile acid molecules
 
have both
a hydrophilic and a hydrophobic end
. In aqueous solutions they aggregate toform micelles, with their hydrophobic (lipid-soluble) ends in the centre. Micelles are expandedby cholesterol and phospholipids (mainly lecithin), forming mixed micelles.Bilirubin metabolismBilirubin is produced mainly from the breakdown of mature red cells in the
Kupffer cells
andin
the reticuloendothelial
system; 15% of bilirubin comes from
the catabolism of other haem-containing proteins
,
such as
myoglobin, cytochromes and catalases.Normally
,
250-300 mg (425-510 mmol)
of bilirubin is produced daily. The iron and globin areremoved from the haem and are reused.
B
iliverdin
is formed from the haem and this isreduced to form bilirubin. The bilirubin produced is
unconjugated and water-insoluble
, dueto internal hydrogen bonding, and is transported to the liver attached to albumin. Bilirubindissociates from albumin and is taken up by the hepatic cell membrane and transported to the
endoplasmic reticulum
by cytoplasmic proteins, where it is conjugated with
glucuronic acid
 and excreted into bile.
The microsomal enzyme
,
uridine diphosphoglucuronosyl (UD
PG)
 transferase
,
catalyses the formation of bilirubin
mono
glucuronide and then
di
glucuronide.
This conjugated bilirubin is water-soluble
and is actively secreted into the bile canaliculiand excreted into the intestine within the bile. It is
not absorbed
from the small intestinebecause of its large molecular size.
I
n the terminal ileum
, bacterial enzymes hydrolyse themolecule, releasing free bilirubin which is then reduced to
urobilinogen.
Some of this isexcreted in the stools as
stercobilinogen
.
The remainder is absorbed by the terminal

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