International Journal of Research in Pharmacy and Biosciences

Volume 4, Issue 8, 2017, PP 13-24

ISSN 2394-5885 (Print) & ISSN 2394-5893 (Online)

Physiology of the liver

Ozougwu, Jevas C. Ph.D
Physiology and Biomedical Research unit, Department of Biological Sciences, College of Basic and
Applied Sciences, Rhema University, Nigeria.
*Corresponding Author: Ozougwu, Jevas C, Physiology and Biomedical Research unit, Department
of Biological Sciences, College of Basic and Applied Sciences, Rhema University, Nigeria.

Received Date: 27-09-2017 Accepted Date: 11-10-2017 Published Date: 14-10-2017

ABSTRACT
In this paper the functions of the liver was summarized which includes firstly, Secretion of bile, the liver
assists intestinal digestion by secreting 700 to 1200 ml of bile per day. Bile is an alkaline, bitter-tasting,
yellowish green fluid that contains bile salts (conjugated bile acids), cholesterol, bilirubin (a pigment),
electrolytes and water. It is formed by hepatocytes and secreted into the canaliculi. Bile salts, which are
conjugated bile acids, are required for the intestinal emulsification and absorption of fats. Secondly,
Metabolism of bilirubin which is a byproduct of destruction of aged red blood cells and gives bile a
greenish black color and produces the yellow tinge of jaundice. Also Vascular and hematologic
functions,because of its extensive vascular network, the liver can store a large volume of blood. The
amount stored at anyone duration depends on pressure relationships in the arteries and veins. Moreover,
the liver has hemostatic functions, It synthesizes prothrombin, fibrinogen, and clotting factors. Vitamin K, a
fat-soluble vitamin, is essential for the synthesis of other clotting factors. Because bile salts are needed for
reabsorption of fats, vitamin K absorption depends on adequate bile production in the liver. Furthermore
Metabolism of nutrients, the liver plays essential roles in the metabolism of fat, protein and carbohydrates.
Also, Metabolic detoxification, the liver alters exogenous and endogenous chemicals (e.g. drugs), foreign
molecules, and hormones to make them less toxic or less biologically active. This process, called metabolic
detoxification, diminishes intestinal or renal tubular reabsorption of potentially toxic substances and
facilitates their intestinal and renal excretion. In this way alcohol, barbiturates, amphetamines, steroids
and hormones (including estrogens, aldosterone, antidiuretic hormone, and testosterone) are metabolized
or detoxified, preventing excessive accumulation and adverse effects. Also, Storage of minerals and
vitamins, the liver stores certain vitamins and minerals, including iron and copper, in periods of excessive
intake and releases them in periods of need. The liver can store vitamins B12 and D for several months and
vitamin A for several years. The liver also stores vitamins E and K. Iron is stored in the liver as ferritin, an
iron-protein complex and is released when needed for red blood cell production. Finally, the liver has
immunologic functions as the liver contain cells involved in adaptive and innate immunity.
Keywords: Liver, Physiology, Functions, Lobule, Hepatocytes.

INTRODUCTION damages such as fatty liver, liver fibrosis and

cirrhosis.
The liver is the largest solid organ, the largest
gland and one of the most vital organs that Origin of the Liver
functions as a centre for metabolism of nutrients The cells that will eventually make up the adult
and excretion of waste metabolites [1]. Its liver originated during embryogenesis from the
primary function is to control the flow and ventral foregut definitive endoderm [4] . The
safety of substances absorbed from the digestive different developmental stages of the liver
system before distribution of these substances to involves establishment of competence for liver
the systemic circulatory system [2]. A total loss formation, after which liver specification,
of liver function could leads to death within hepatic bud formation, growth and finally
minutes, demonstrating the liver‘s great differentiation will occur [5]. During the
importance [3], in view of this, this study was development of the liver, as well as certain
undertaken to review the physiology of the liver duration after partus, the metabolic profile of the
with a view to keep it functioning at its optimum young liver is far from that of the adult
and maintaining good health so as to avoid liver

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Physiology of the liver

phenotype. Prior to birth, and shortly thereafter, that the liver is divided into 4 lobes: right, left,
many metabolic changes occur in the liver [6]. caudate, and quadrate. The right and left lobes
These allow the organism to adapt to uptake of are the largest, while the caudate and quadrate
nutrients from food, but also change its ability to are smaller and located posteriorly. Two
metabolize xenobiotics. As the organism ligaments are visible anteriorly. Superiorly, the
matures, with duration an adult pattern of falciform ligament separates the right and left
metabolic enzymes develops. During the lobes. Inferior to the falciform ligament is the
development of the hepatocellular carcinoma, round ligament, which protrudes from the liver
frequently the gene expression pattern of the slightly. Also visible anteriorly on the most
hepatocytes reverts to a more fetal-like stage inferior portion of the right lobe is the
[7]. In certain cases this leads to the expression gallbladder. Posteriorly, many more interesting
of metabolic enzymes otherwise found only structures are visible. [2] reported that the
during embryogenesis. This partly fetal-like caudate lobe is located superiorly,
expression pattern is also noticeable in many approximately between the right and left lobes.
human hepatoma cell lines that are often used Adjacent to the caudate lobe is the sulcus for the
for in vitro toxicology studies inferior vena cava. Just inferior to the caudate
lobe is the porta hepatis, where the hepatic
General Description of the Liver
artery and hepatic portal vein enter the liver.
The liver weighs approximately 1500g and The portal vein carries nutrient laden blood from
accounts for approximately 2.5% of adult body the digestive system. Inferior to the porta
weight [8]. The surface of the liver is smooth hepatis is the bile duct which leads back to the
and dome shaped, where it is related to the gallbladder. [2] also explained that the hepatic
concavity of the inferior surface of the vein, where post-processed blood leaves the
diaphragm. (Figure 1) The liver lies mainly in liver, is found inferior and adjacent to the sulcus
the right upper quadrant of the abdomen where for the inferior vena cava. The liver is held on
it is hidden and protected by the thoracic cage place by a system of mesenteries posteriorly,
and diaphragm. The normal liver lies deep to the and is also attached to the diaphragm via the
ribs 7 – 11 on the right side and crosses the falciform ligament. Additionally, most of the
midline towards the left nipple [8]. [2] explained liver is covered by visceral peritoneum.

Figure1. Diagram of the liver showing the right and left lobes and its posterior and anterior veiws. Source :
Encyclopedia Britannica, 2010

Histology of the Liver  Portal triads at each corner of hexagon

The basic functional unit of the liver is the liver  Central vein
lobule (Figure 2, Figure 3). A single lobule is  Liver sinusoids that run from the central vein
about the size of a sesame seed and is roughly to the portal triads
hexagonal in shape. [2] explained that the
primary structures found in a liver lobule  Hepatic macrophages (Kupffer cells)
include:  Bile canaliculi (―little canals‖) – formed
between walls of adjacent hepatocytes
 Plates of hepatocytes which forms the bulk
of the lobule

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Physiology of the liver

 Space of Disse – a small space between the the inferior vena cava. Secreted bile flows in the
sinusoids and the hepatocytes opposite direction – through the bile canaliculi
away from the central vein, toward the portal
The portal triads consist of three vessels: a
triad, and exiting via the bile duct. As blood
hepatic portal arteriole, a hepatic portal venule,
flows through the sinusoids and the space of
and a bile duct. The blood from the arteriole and
disse toward the central vein, nutrients are
the venule both flow in the same direction –
processed and stored by the hepatocytes, and
through the sinusoids toward the central vein,
worn out blood cells and bacteria are engulfed
which eventually leads to the hepatic vein and
by the Kupffer cells [2].

Figure2. Cellular architecture of the liver. (A) The schematic shows an adult liver (red), with the gall bladder
and extra hepatic ducts (green), in relation to the stomach and intestine (yellow). The extra hepatic duct system
consists of the hepatic ducts (hd), which drain bile from the liver into the common hepatic duct (chd) to the gall
bladder via the cystic duct (cd) and into the duodenum through the common bile duct (cbd). (B) A schematic of
the cellular architecture of the liver showing the hepatocytes (pink) arranged in hepatic plates separated by
sinusoid spaces radiating around a central vein. Bile canaliculi on the surface of adjoining hepatocytes drain
bile into the bile ducts (green), which run parallel to portal veins (blue) and hepatic arteries (red) to form the
“portal triad”.
Source: Zorn, 2013.

Figure3. Diagram Showing Liver Lobules.

Source: [9]

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Physiology of the liver

Figure4. Basic Structure Of Liver Lobule. Sources : Arora, 2012

The liver is the first site of passage for venous types. Four main cell types will be discussed for
blood arriving from the intestines via vena porta the purpose of this paper, namely:
[10]. The areas around the influx blood vessels
 Hepatocytes
are named periportal. The areas surrounding
efflux blood vessels are the perivenous. The  Endothelial cells
periportal area is highly complex and consists of
a dense matrix containing collagen where  Kupffer cells (liver resident macrophages)
afferent blood vessels are found, together with and
bile ducts, nerve and lymph [10]. Spaces within  Stellate cells (liver fat storing cells). (Figure
the matrix contain a variable cell population, 5)
such as fibroblasts, hematopoietic cells and
inflammatory cells. Also found here are Hepatocytes
epithelial cells of the bile ducts, endothelial cells Hepatocytes represent 60 % of the liver‘s cells
of the blood vessels, and smooth muscles of and about 80 % of the liver‘s total cell mass.
arteries and veins [11]. The liver lobule consists Most of the liver‘s synthetic and metabolic
mainly of plates of hepatocytes and sinusoids, capabilities stem from the work of hepatocytes
with a light matrix of collagen to form a [2]. Hepatocytes are arranged in plates only a
network between the two. Kupffer cells, as well single cell thick [9]. (Figure 5) Blood flowing
as fat storing stellate cells are found toward the hepatic vein within the space of
here.(Figure 4) These types of cells reside Disse passes both exposed surface areas of the
mainly in the tissue space between the hepatocyte plates and toxins and nutrients
hepatocyte and the sinusoids. Terminal bile within the blood are extracted by the
ductules connect here to the bile cannaliculi hepatocytes. Hepatocytes are large and rich in
between hepatocystic plates [11]. The walls of organelles such as endoplasmic reticulum and
the hepatic sinusoid are lined by three different Golgi apparatuses. They contain many and large
cell types: the sinusoidal endothelial cells, mitochondria, as well as lysosomes and
kupffer cells and stellate cells. Additionally, pit peroxisomes [14]. The main function of
cells, the liver specific natural killer (NK) T hepatocytes is to participate in lipid,
cells are often present in the sinusoidal lumen carbohydrate and protein metabolism. They also
[12]. The main parenchymal mass is normally produce serum proteins such as albumin and
that of hepatocytes. In rat, the hepatocytes make coagulation factors [15]. Furthermore,
up about 60 % of liver cell count and the hepatocytes produce and secrete bile as well as
remaining 40 %, non-parenchymal cells only detoxify and excrete cholesterol, steroid
make up for about 6 -7 % of the liver volume hormones and xenobiotic drugs. Numerous
while the remaining volume of approximately xenobiotics are metabolized by the mixed-
23 % is formed by extracellular spaces [13]. functions of monooxidases found in hepatocytes
The liver is made up of many different cell [16]. Structure and function of the hepatocytes
within the liver lobule differs greatly depending

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Physiology of the liver

on proximity to periportal or perivenous areas. receptors that enable them to bind cells covered
Periportal type of hepatocytes are often smaller, with immunoglobulins or bind to complement
but have larger mitochondria, and a larger Golgi receptors and subsequently phagocytose cell
apparatus as compared to the perivenous type. [21]. Kupffer cells are even actively phagocytic
Perivenous hepatocytes on the other hand have in vitro and contain high levels of peroxidase,
larger endoplasmic reticulum. Functionally, acid phosphatase and glucose 6-phosphate
periportal hepatocytes are more involved in dehydrogenase [22].
gluconeogenesis, while perivenous are involved
Stellate Cells
in glycolysis [10]. Additionally, perivenous
hepatocytes are dorminant with respect to P The liver plays a central role in uptake and
450- dependent hydroxylation reactions [17] storage of vitamins A (Retinol) and stores about
and glutamine synthetase [18]. 95 % of retinoids found in the body. The fat
storing perisinusoidal cells of the liver, stellate
Endothelial Cells
cells are the main vitamin A storing cells
The sinusoidal endothelial cells line the walls of (Figure 5). They harbor large amounts of retinol
the hepatic sinusoid and perform a function of and retinyl palmitate in lipid droplets within
filtration due to the presence of fenestrae [10]. their cell cytoplasm [23]. They are located in the
(Figure 5) These cells also demonstrate large space of Disse (between hepatocytes and
endocytic capacity for extracellular matrix sinusoid) and generally protrude to come into
components and immune complexes. In general contact with several sinusoids [23].
they engulf smaller size particles and may play a Additionally, they function to control the
role in clearance of viruses, but do not posses turnover of extracellular matrix and regulate
phagocytic function [19]. They may also sinusoid contractility. The stellate cells may
function as antigen presenting cells and secrete become activated under stressful conditions and
certain cytokines and eicosanoids [12]. transformed into myofibroblast – like cells
which play a key role in inflammatory fibrotic
Kupffer Cells
response [12]. When activated, stellate cells not
The liver harbors large amounts of kupffer cells, only proliferate, but also produce increased
which represent the largest tissue resident amounts of extracellular matrix per cell.
macrophage population of the body [20]. Transforming growth factor beta (TGF β) is one
(Figure 5). They are located within the sinusoid of the most important signals to activate stellate
and are in constant contact with gut-derived cells, which leads to a higher transcriptional rate
particles that lead to low but constant amount of of mRNAs coding for extracellular matrix
activation of these monocyte derived cells. components such as collagen I, fibronectin and
Upon activation they are able to secrete a vast proteoglycans [10]. Lipid peroxidation products
range of inflammatory mediators such as are also an important stimulus, whose effect
cytokines, reactive oxygen species, eicosanoids may be augmented in oxidative stress conditions
and nitric oxide [12]. Kupffer cells have [24].

Figure5. Diagram showing main cell types of Liver - hepatocytes, endothelial cells, Kupffer cells and Stellate
cells. Source: Tissupath specialist pathway services, Retrieved 2017. www. Tissupath.com.au

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Physiology of the liver

FUNCTIONS OF THE LIVER

The liver has numerous functions best grouped into secretion of bile, metabolism of bilirubin,
vascular and hematologic functions, metabolism of nutrients, metabolic detoxification and storage of
minerals and vitamins. (Table 1)
Table1. Summary Of Major Functions Of The Liver
Secretion of Bile
Metabolism of Bilirubin
Vascular and Hematologic Functions
 Important blood reservoir
Metabolism of Nutrients
 Fat - fatty acid oxidation, synthesis of cholesterol/lipoproteins and production of ketoacids
 Protein – Amino acid production, turnover of proteins
 Carbohydrate – converts galactose/fructose to glucose, gluconeogenesis and contains 100g of glycogen
for release
Metabolic Detoxification
 Toxins
 Hormones
 Drugs
Storage of Minerals and Vitamins
 Iron
 Copper
 Vitamins ADEKB12
 Glycogen
Endocrine functions
 Activation of vitamin D
 Conversion of thyroxine (T4) to T3
 secretes angiotensinogen
 metabolises hormones
Immunological/ Protective Functions
Reticuloendothelial Component
 Filters the portal blood from bacteria
 Important in antigen presentation
 Phagocytosis via kupffer cells
 Removes haemolysis products
Inactivation Of Toxins and Drugs
 Phase I (oxidation, reduction and hydrolysis)
 Phase II (conjugation/ cytochrome P450 system)
[25] and [8] explained the functions of the liver as follows:
Secretion of Bile the bile acid-dependent fraction of the
The liver assists intestinal digestion by secreting bile. This fraction consists of bile acids,
700 to 1200 ml of bile per day. Bile is an cholesterol, lecithin (a phospholipid), and
alkaline, bitter-tasting, yellowish green fluid that bilirubin (a bile pigment). The bile acid-
contains bile salts (conjugated bile acids), independent fraction of the bile, which is
cholesterol, bilirubin (a pigment), electrolytes secreted by the hepatocytes and epithelial
and water. It is formed by hepatocytes and cells of the bile canaliculi, is a
secreted into the canaliculi. Bile salts, which are bicarbonate-rich aqueous fluid that gives
conjugated bile acids, are required for the bile its alkaline pH.
intestinal emulsification and absorption of fats.
Having facilitated fat emulsification and  Bile salts are conjugated in the liver from
absorption, most bile salts are actively absorbed primary and secondary bile acids. The
in the terminal ileum and returned to the liver primary bile acids are cholic acid and
via the portal circulation for resecretion as chenodeoxycholic (chenic) acid. These
follows: acids are synthesized from cholesterol by
 Bile has two fractional components: the the hepatocytes. The secondary bile acids
acid-dependent fraction and the acid- are deoxycholic acid and lithocholic acid.
independent fraction. Hepatocytes secrete These acids are formed in the small

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Physiology of the liver

intestine by the action of intestinal is then excreted in the urine, and a small
bacteria, after which they are absorbed amount is eliminated in feaces.
and flow to the liver. Vascular and Hematologic Functions
 Both forms of bile acids are conjugated Because of its extensive vascular network, the
with amino acids in the liver to form bile liver can store a large volume of blood. The
salts. amount stored at any one duration depends on
pressure relationships in the arteries and veins.
 Conjugation makes the bile acids more
water soluble, thus restricting their  The liver can also release blood to maintain
diffusion from the duodenum and ileum. systemic circulatory volume in the event of
hemorrhage.
Metabolism of Bilirubin
 Kupffer cells in the sinusoids of the liver
Bilirubin is a byproduct of destruction of aged remove bacteria and foreign particles from
red blood cells. It gives bile a greenish black the portal blood. Because the liver receives
color and produces the yellow tinge of jaundice. all of the venous blood from the gut and
 Aged red blood cells are taken up and pancreas, the Kupffer cells play an important
destroyed by macrophages of the role in destroying intestinal bacteria and
preventing infections.
mononuclear phagocyte system,
primarily in the spleen and liver (in the  The liver also has hemostatic functions. It
liver these macrophages are Kupffer synthesizes prothrombin, fibrinogen, and
cells). Within these cells hemoglobin is clotting factors. Vitamin K, a fat-soluble
separated into its component parts— vitamin, is essential for the synthesis of other
heme and globin. The globin component clotting factors. Because bile salts are needed
for reabsorption of fats, vitamin K absorption
is further degraded into its constituent
depends on adequate bile production in the
amino acids, which are recycled to form liver.
new protein. The heme moiety is
converted to biliverdin by the enzymatic Metabolism of Nutrients
cleavage of iron. The iron attaches to  Fats: Fat is synthesized from carbohydrate
transferrin in the plasma and can be and protein, primarily in the liver. Fat
stored in the liver or used by the bone absorbed by lacteals in the intestinal villi
marrow to make new red blood cells. The enters the liver through the lymphatics,
biliverdin is enzymatically converted to primarily as triglycerides. In the liver the
bilirubin in the macrophage of the triglycerides can be hydrolyzed to glycerol
mononuclear phagocytic system and then and free fatty acids and used to produce
is released into the plasma. In the plasma, metabolic energy adenosine triphosphate
(ATP), or they can be released into the
bilirubin binds to albumin and is known bloodstream as lipoprotein. The lipoproteins
as unconjugated bilirubin or free are carried by the blood to adipose cells for
bilirubin, which is lipid soluble. storage. The liver also synthesizes
 In the liver, unconjugated bilirubin phospholipids and cholesterol, which are
moves from plasma in the sinusoids into needed for the hepatic production of bile
salts, steroid hormones, components of
the hepatocyte. Within hepatocytes, it plasma membranes and other special
joins with glucuronic acid to form molecules.
conjugated bilirubin, which is water
soluble. Conjugation transforms bilirubin  Proteins - The plasma proteins, including
from a lipid-soluble substance that can albumins and globulins (excluding gamma-
globulin), are synthesized by the liver. The
cross biologic membranes to water-
liver also synthesizes several non essential
soluble substance that can be excreted in amino acids and serum enzymes including
the bile. When conjugated bi1irubin aspartate aminotransferase, alanine
reaches the distal ileum and colon, it is aminotransferase, lactate dehydrogenase and
deconjugated by bacteria and converted alkaline phosphatase.
to urobilinogen. Most of the urobilinogen

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Physiology of the liver

 Carbohydrates: The liver contributes to the phase I reaction is induced, this may leave the
stability of blood glucose levels by releasing organism with an excess of reactive molecules
glucose during states of hypoglycemia (low from the phase I reaction, which can be
blood sugar) and taking up glucose during detrimental. This can occur in the case of drug
states of hyperglycemia (high blood sugar) induced hepatotoxicity, when reactive
and storing it as glycogen (glyconeogenesis) metabolites of the parent compound are formed,
or converting it to fat. When all glycogen which subsequently negatively affects cellular
stores have been used, the liver can convert functions [27].
amino acids and glycerol to glucose. Storage of Minerals and Vitamins
Metabolic Detoxification The liver stores certain vitamins and minerals,
The liver alters exogenous and endogenous including iron and copper, in durations of
chemicals (e.g. drugs), foreign molecules, and excessive intake and releases them in durations
hormones to make them less toxic or less of need. The liver can store vitamins B 12 and D
biologically active. This process, called for several months and vitamin A for several
metabolic detoxification, diminishes intestinal years. The liver also stores vitamins E and K.
or renal tubular reabsorption of potentially toxic Iron is stored in the liver as ferritin, an iron-
substances and facilitates their intestinal and protein complex and is released as needed for
renal excretion. In this way alcohol, red blood cell production.
barbiturates, amphetamines, steroids and
The Immunologic Function of the Liver
hormones (including estrogens, aldosterone,
antidiuretic hormone, and testosterone) are The liver is the main hematopoietic organ
metabolized or detoxified, preventing excessive during certain stages in fetal development and
accumulation and adverse effects. Although continues to be a hematopoietic organ even after
metabolic detoxification is usually protective, in birth. It can produce all leukocytes lineages
some durations the products of metabolic from resident hematopoietic stem cells [28, 29].
detoxification become toxins. Those of alcohol The portal tract of the liver contains many
metabolism, for example, are acetaldehyde and different cells of hematopoietic origin, as well
hydrogen. Excessive intake of alcohol over a as hematopoietic stem cells [11]. The liver
prolonged period causes these end products to contains cells involved in adaptive and innate
damage the hepatocytes. Acetaldehyde damages immunity.
cellular mitochondria, and the excess hydrogen Innate Immunity of the Liver
promotes fat accumulation. This is how alcohol
impairs the liver‘s ability to function. In comparison to other organs, the liver is
particularly rich in cells of the innate immune
The adult liver is the main organ responsible for system. The main cell types here are kupffer
detoxifying and metabolizing a variety of cells and NK T cells. NK T cells are not strictly
exogenous as well as endogenous compounds, part of innate immunity but functionally
rendering them more hydrophilic, which often somewhere in between adaptive and innate. Of
affects their potency and level [10]. The hepatic lymphocytes, approximately 30 % are
enzymes responsible for the actions are NK cells, indicating the great contribution of
primarily produced in hepatocytes and mainly NK cells to liver immunity. This may be
divided into two groups phase I and phase II. compared to the approximately 15% that the two
The phase I enzymes are predominantly from cell types combined contribute to in peripheral
the P- 450 family of genes, whose general blood lymphocytes [30]. NK cells are one of the
function is to add polar groups, such as hydroxyl main producers of liver INFγ in response to
groups, to lipophilic molecules thus rendering lipopolysaccharide (LPS), which partly depends
them more hydrophilic [26]. The main function on the activation of NK cells by IL-I2 derived
of the phase II enzymes is to covalently attach a from activated Kupffer cells. They show high
water soluble moiety to the polar group added cytotoxic level towards tumor cells, with the
by the phase I enzymes. Usually such molecules help of the trail-ligand, which is up regulated by
are sugars or peptides, such as glucuronic acid IL-2. Kupffer cells are derived from circulating
or glutathione. This usually renders the monocytes and play a particularly important role
compound less reactive. Examples of phase II in initiating inflammation in the liver. Kupffer
enzymes are glutathione-S-transferase and cells differ in properties depending if they are
UDP– glucuronosyl transferase. If the phase II periportal or perivenous. Periportal cells are
reaction is impaired for some reasons or the larger and more active in phagocytosis,

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Physiology of the liver

mirroring their function as the first line of have been shown to ‗crawl‘ within the hepatic
defense of the body towards gut derived bacteria sinusoid, and stop upon T cell antigen receptor
entering the blood stream and reaching the liver activation [41]. Naïve CD8+ T cells are also
via the vena porta [31] . Perivenous kupffer cells known to accumulate in the liver, where they
on the other hand, are smaller and produce may be activated, but at durations to a lesser
larger amounts of nitric oxide, as well as degree than in lymph nodes. Thus, low-grade
prostaglandins [32]. Ex vivo culture of kupffer activation of T cells in liver rather leads to
cells have shown that the perivenous type tolerance [42]. There is also evidence for
secretes more than double the amount of TNF α regulatory T cells expressing IL-10 [36]. B cells
upon LPS stimulation. Kupffer cells are one of have not been well studied in adult liver,
the main cell types to secrete cytokines, which however, there is a substantial B cell population
then regulate the function not only of the showing similarities to splenic B cells. It has
kupffer cells themselves but also that of other been shown that B cells play a role in liver
cell types such as the NK cells. Stimulation of fibrosis, as B cell deficient mice show
kupffer cells by bacteria and bacterial LPS leads significantly less fibrotic lesions after carbon
to production of IL-12 [33] , as well as TNFα. tetrachloride induced liver injury. This effect is
Other cytokines known to be produced by independent of antibody production. But also B
kupffer cells upon LPS stimulation include IL-6, cell antibody-dependent responses play a part in
TGF β, IL-1β and IL-8 [34]. Cytokines derived liver injury, as antibody production has been
from kupffer cells have in turn been proven to shown to be of importance in alcohol induced
stimulate hepatocytes to further increase liver damage [43].
chemotactic response by secretion of IL-8 [35].
Interrelationships of the Liver with Other
Thus kupffer cells and NK cells hence mainly
Organs
secrete Th1 type cytokines that activate the
immune system. Immunosuppressive cytokines The liver interacts with many other organs.
such as IL-10 may instead be secreted by Following the flow of blood, the liver receives
stellate cells and regulatory T cells (but also by its arterial blood supply from the hepatic arteries
kupffer cells and NK cells) [36]. [3]. The hepatic arteries are distal to the celiac
trunk, which is distal to the abdominal aorta.
Adaptive Immunity
Thus the liver receives its oxygenated blood
Adaptive immunity can be classified into supply from the heart. Nutrient laden blood
humoral immunity and cell-mediated immunity, from the digestive system and blood leaving the
mediated principally by B and T lymphocytes, spleen enters the liver through the hepatic portal
respectively. T cells promote differentiation of vein . Processed blood leaving the liver through
B cells to antibody secreting plasma cells. T the hepatic veins drains into the inferior vena
cells kill infected cells and secrete cytokines cava, completing the connection to the heart.
such as TNF α, IFN γ and IL -6. TNF α derived The liver affects digestion through its formation
from kupffer cells play an important role in of bile, which is secreted into the small intestine
stimulating activation of T cells which then [2]. The gallbladder is essentially an overflow
elicit a cytotoxic response [37]. Intrahepatic area for the liver‘s bile duct. The liver is full of
accumulation of highly activated CD8+ T cells lymph glands, which provide fluid drainage and
is part of the pathogenesis process in hepatitis, immune system support. The liver synthesizes
including alcoholic hepatitis [38]. NK T cells many blood proteins, showing its relation to that
constitute a distinct subpopulation of T cells that ―organs‖. The liver also has a supply of nerves,
is particularly abundant in the liver, as showing its relationship with the nervous
previously mentioned. Infact, they are not system. Finally, liver disease often causes
strictly a part of adaptive immune response, but problems in the renal system, demonstrating a
can be seen as having a function in between relationship with the kidneys [2]. The liver has
adaptive and innate immunity. These cells many important functions in maintaining the
produce large amounts of the Th 2 cytokine IL-4 physiologic balance of the human body.
[39] but also the Th1 cytokine IFN γ [40]. This
ability of secreting both Th 1 and Th 2 type CONCLUSIONS
cytokines is particularly feature of NK cells. NK In conclusion this paper summarized the
T cells are often present in the lumen of the functions of the liver which includes firstly,
sinusoid. They exhibit MHC- unrestricted Secretion of bile, the liver assists intestinal
killing of a variety of tumor cells, an level digestion by secreting 700 to 1200 ml of bile per
which is enhanced by IFN γ [12]. NK T cells day. Bile salts, which are conjugated bile acids,

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Physiology of the liver

are required for the intestinal emulsification and extracts against paracetamol-induced liver
absorption of fats. Secondly, Metabolism of damage in Rattus novergicus. 2014 Ph.D
bilirubin which is a byproduct of destruction of Research Thesis, Department Of Zoology and
aged red blood cells and gives bile a greenish Environmental Biology, University of Nigeria,
black color and produces the yellow tinge of Nsukka. 222pp
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Citation: J. Ozougwu, "Physiology of the liver", International Journal of Research in Pharmacy and
Biosciences, vol. 4, no. 8, pp. 13-24, 2017.
Copyright: © 2017 J. Ozougwu. This is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited.

24 International Journal of Research in Pharmacy and Biosciences V4 ● I8 ● 2017