Main functions of these glands
• Products of these organs facilitate transport and 
digestion of food within the gastrointestinal 
tract.
• Salivary glands moisten and lubricate ingested 
food and the oral mucosa, to initiate the 
digestion of carbohydrates and lipids with 
amylase and lipase, and to secrete innate 
immune components such as lysozyme and 
lactoferrin• The pancreas secretes digestive enzymes that act 
in the small intestine and hormones important for 
the metabolism of the absorbed nutrients
• Bile, whose components are necessary for 
digestion and absorption of fats, is made in the 
liver but stored and concentrated in the 
gallbladder 
• Liver also plays a major role in carbohydrate and 
protein metabolism, inactivates many toxic 
substances and drugs, and synthesizes most 
plasma proteins and factors necessary for blood 
coagulation SALIVARY GLANDS 
• There are 3 pairs of 
large salivary glands: 
• parotid, submandibular, 
and sublingual glands
• Together produce about 
90% of saliva 
• in addition numerous 
minor or intrinsic 
salivary glands located 
throughout most of the 
oral mucosa (Labial and 
buccal, Glossopalatine, 
Palatine, Lingual)
which secrete about 10% 
of the total saliva volume
Parotid salivary gland
Sublingual salivary gland
Submandibular salivary glandType of secretion 
• The secretion of each gland is either :
• Serous, seromucous, or mucous
• parotids is serous and watery 
• Submandibular and sublingual glands produce 
a seromucous secretion 
• Minor glands is mostly mucous except for the 
small serous glands at the bases of 
circumvallate papillaeThree epithelial cell types comprise 
the salivary secretory units
• Serous cells : 
• are protein-secreting cells
• usually pyramidal in shape, with basal round nuclei, 
well-stained RER, and apical secretory granules 
• Joined apically by tight and adherent junctions, 
• serous cells form a somewhat spherical unit called an 
acinus with a very small central lumen
• Serous acini are intensely stained (pink-purple) due 
to their protein content( basal basophilic & apical 
acidophilic)
• Serous acinar cells secrete enzymes such as alphaamylase, which catalyzes the hydrolysis of starch into 
simpler sugars like maltose • Mucous cells :
• are more columnar in shape, with more 
compressed flat basal nuclei 
• Mucous cells contain apical granules with hydro 
philic mucins that provide lubricating properties 
• More weakly stains than serous acini
• Cytoplasm appears pale, foamy
• Stains like PAS (Periodic Acid-Schiff) or Alcian blue 
can highlight the carbohydrate-rich mucins in 
mucous acini, appearing reddish-pink or pale blue, 
respectively
• Mucous cells are most often organized as 
cylindrical tubules rather than acini
• mucous also acts as a barrier against pathogensStructural organization of salivary glandSerous demilune
• Within the mixed 
units grouped 
serous cells occur 
distally on short 
mucous tubules 
and often assume a 
crescent-shaped 
arrangement called 
a serous demilune• Myoepithelial cells:
• are found inside the basal lamina surrounding 
acini, tubules, and the proximal ends of the duct 
system
• These cells are present between the basal 
lamina and the secretory or duct cells and are 
joined to the cells by desmosomes 
• They appear similar to smooth muscle but are 
derived from the epithelium
• Have stellate-shaped, numerous branching 
processes with a flattened nucleus extend 
several contractile processes around the 
associated secretory unit or duct Function of myoepithelial cells 
• their activity is important for moving secretory 
products into and through the ducts
• accelerate the initial flow of saliva from the acini, 
reduce luminal volume
• support the underlying parenchyma, 
• reduce the back permeation of fluid
• They secrete various tumor suppressor proteins 
such as protease inhibitors and antiangiogenesis
factors which provide a barrier against invasive 
epithelial neoplasm.Duct system
• It consists of hollow tubes that connect initially with the 
acinus (secretory end pieces) and extends to the oral 
cavity 
• it actively participates in the production and modification 
of saliva
• On the basis of location, ducts are of two types:
• Intralobular ducts: Those ducts which are within the 
lobule
• intercalated 
• striated ducts
• Interlobular ducts: Those ducts which lie within the 
connective tissue within the lobules of the gland
• The excretory ductsIntercalated ducts
• These are lined by single layer of cuboidal epithelium 
and are surrounded by myoepithelial cell bodies, 
• have centrally placed nuclei 
• A few secretory granules may be found in the apical 
cytoplasm, especially in the cells located near the 
endpieces
• The apical cell surface has a few short microvilli 
projecting into the lumen
• lateral surfaces are joined by junctional complexes
• The macromolecule components, i.e., lysozyme and 
lactoferrin, are stored in the secretory granules of the 
intercalated duct and contribute to the saliva.
– Lactoferrin binds iron, a vital nutrient for many microbes and 
disrupting microbial membranes
– Lysozyme hydrolyzes the cell wallStriated ducts
• Several of intercalated ducts join to form a 
striated duct 
• Striated ducts lined by columnar cells with a 
centrally placed large, spherical nucleus and pale, 
acidophilic cytoplasm. 
• By EM basal infoldings of the plasma membrane 
• a large amount of radially oriented mitochondria 
• The combination of infoldings and mitochondria 
accounts for the striations seen in the light 
microscopeFunction of striated ducts
• their folded cell membranes present a large 
surface area with ion transporters, facilitating 
rapid ion transcytosis and making the secretion 
slightly hypotonic
• These ducts are involved in active transport and 
are considered as site of electrolyte reabsorption 
especially of sodium and chloride and secretion 
of potassium and bicarbonate• A striated duct 
shows very faint 
striations in the 
basal half of the 
columnar cells, 
which represent 
mitochondria 
located in the 
folds of the lateral 
cell membrane Inter lobular excretory ducts
• These ducts are located in the CT septa between the 
lobules of the gland 
• are larger in diameter than striated duct
• The lining of these ducts is unusual, combining 
various epithelial types, including simple cuboidal or 
columnar, stratified cuboidal or columnar, and 
pseudostratified epithelia, distributed in no apparent 
pattern. 
• These atypical epithelia may reflect their 
composition of cells with many diverse functions, 
including cells for ion reabsorption, cells for 
secretion of mucin and other proteins, 
enteroendocrine cells, and basal stem cells• The main excretory duct may become stratified near the 
oral opening
• Before emptying into the oral cavity, the main duct of each 
gland is lined with nonkeratinized stratified squamous 
epithelium 
• Tuft or brush cells found in the lining of epithelial tissues, 
including the duct system
• These cells have long stiff microvilli and apical vesicles and 
are considered as chemoreceptor cells as they show nerve 
endings adjacent to the basal portion of the cell
• Dendritic cells are found in various parts of the gland, 
including the ducts, acini, and interstitial tissues play an 
important role in immune surveillance (antigen 
presentation)Histology of serous glandHistology of mixed glandSaliva has protective function
• Plasma cells in CT surrounding the intralobular
ducts release IgA, which forms a complex with 
the secretory component synthesized by the 
epithelial cells of the serous acini and 
intralobular ducts. 
• The IgA complex released into the saliva 
provides defense against specific pathogens in 
the oral cavityThe functions of saliva are:
Protection:
– Lubricant
– Mechanical washing
• Buffering:
_ Many bacteria need a specific pH for growth; saliva prevents 
potential pathogens from colonizing in the mouth by denying them 
optimal environmental conditions.
– Plaque microorganisms can produce acids from sugars, which if 
not rapidly buffered and cleared by saliva can demineralize 
enamel.
• Digestion: It provides taste acuity, neutralizes esophageal contents, 
and forms the food bolus.
• Taste: It dissolves substances to be carried to taste buds and also 
contains a protein, called gustin, which is necessary for growth and 
maturation of taste buds.• Antimicrobial action: This occurs in various ways as:
– Lactoferrin binds free iron deprives bacteria of its essential 
element
– Lysozyme hydrolyzes the cell wall.
– Histatin proteins with antibacterial property.
– Immunoglobulin, secretory IgA, clumps or agglutinates 
microorganisms.
• Maintenance of tooth integrity: Saliva is saturated with 
calcium and phosphate ions, and interaction with saliva 
results in postoperative maturation through diffusion of 
such ions. This maturation increases surface hardness, 
decreases permeability, and increases the resistance of 
enamel to caries.
• Tissue repair: The rate of wound contraction is 
significantly increased in saliva due to the presence of 
peptides and proteins present in saliva.Saliva production 
• Parasympathetic stimulation, usually elicited 
through the smell or taste of food, provokes a 
copious watery secretion with relatively little 
organic content
• Sympathetic stimulation inhibits such secretion 
and produces the potential for dry mouth often 
associated with anxietyMedical application 
• Inadequate saliva production, leading to dry 
mouth or xerostomia, can be caused by various 
factors affecting the major salivary glands, such 
as mumps viral infection, radiation of the glands, 
or the normal side effect of drugs such as 
antihistamines 
• Excessive saliva production, or sialorrhea, is 
associated with the autonomic activity of nausea, 
inflammation within the oral cavity, and rabies 
viral infectionParotid glands
• located in each cheek near the ear
• are branched acinar glands with exclusively 
serous acini
• Serous cells secrete abundant α-amylase that 
initiates hydrolysis of carbohydrates and 
proline-rich proteins with antimicrobial and 
other protective propertiesMicrograph of a parotid gland shows densely 
packed serous acini (A) Secretory granules of 
serous cells as well as an intercalated duct (ID) 
striated duct (SD)
Striations of a duct (SD) are better seen here, 
along with a septum (CT) and numerous serous 
acini (A). The connective tissue often includes 
adipocytesSubmandibular glands
• produce two-thirds of all saliva
• are branched tubuloacinar glands
• having primarily serous acini, but with many 
mixed tubuloacinar secretory units 
• Within the mixed units grouped serous cells occur 
distally on short mucous tubules and often 
assume a crescent-shaped arrangement called a 
serous demilune
• In addition to α-amylase and proline-rich proteins,
serous cells of the submandibular gland secrete 
lysozyme for hydrolysis of bacterial wallsSublingual glands
• The smallest of the major glands
• are also branched tubuloacinar glands
• secretory tubules of mucous cells 
predominate and the main product of the 
gland is mucus 
• The few serous cells present add amylase and 
lysozyme to the secretion.The submandibular gland is a mixed 
serous and mucous gland (serous cells 
redominate)
The sublingual gland is a mixed but largely 
mucous glandPancreas 
• Is a mixed exocrine-endocrine gland that 
produces both digestive enzymes and hormones.
• with a large head near the duodenum and more 
narrow body and tail regions that extend to the 
left 
• Has a thin capsule of CT from which septa extend 
to cover the larger vessels and ducts and to 
separate the parenchyma into lobules 
• The secretory acini are surrounded by a basal 
lamina that is supported only by a delicate sheath 
of reticular fibers with a rich capillary network. • somewhat resembles the parotid gland 
histologically, although the pancreas lacks 
striated ducts and the parotid glands lack islets of 
endocrine tissue
• Each pancreatic acinus consists of several serous 
cells surrounding a very small lumen, without 
myoepithelial cells 
• The acinar cells have round basal nuclei, and 
numerous zymogen granules apically, typical of 
protein-secreting cells FUNCTION 
• Endocrine function involves smaller cells located 
in variously sized clusters called the pancreatic 
islets (islets of Langerhans)
• Digestive enzymes are produced by cells of 
serous acini in the larger exocrine portion of the 
pancreas DUCT SYSTEM 
• Each acinus is drained 
by a short intercalated 
duct of simple 
squamous or low 
cuboidal epithelium
• The initial cells of these 
small ducts extend into 
the lumen of the acinus
as small pale-staining 
centroacinar cells that 
are unique to the 
pancreas• Under the influence of secretin, the 
centroacinar and intercalated duct cells of the 
intercalated ducts secrete a large volume of 
fluid, rich in HCO3 − (bicarbonate ions), which 
alkalinizes and transports hydrolytic enzymes 
produced in the acini• The intercalated ducts merge with intralobular
ducts that lined with simple columnar epithelium 
• and larger interlobular ducts, which have 
increasingly columnar epithelia before joining the 
main pancreatic duct that runs the length of the 
gland lined with simple columnar epithelium 
• The ducts and blood vessels are located in 
connective tissueMicrograph of exocrine pancreas shows the serous, with very small 
lumens. Each acinus is drained by an intercalated duct with its initial 
cells, the centroacinar cells (arrow), inserted into the acinar lumen. 
(b) The diagram shows the arrangement of cells more clearly..Function of exocrine pancreas
• Is a mixture of : 
• acinar secretion (proenzymes)
• And duct secretion (bicarbonate) 
• The exocrine pancreas secretes approximately 1.5 
L of alkaline pancreatic juice per day and delivers 
it directly into the duodenum where the HCO3− 
ions neutralize the acidic chyme entering there 
from the stomach and establish the pH for 
optimal activity of the pancreatic enzymes• These digestive enzymes include several 
proteases, α-amylase, lipases, and nucleases 
(DNAase and RNAase).
• The proteases are secreted as inactive zymogens 
(trypsinogen, chymotrypsinogen, proelastase, 
and procarboxipeptidases). 
• Trypsinogen is cleaved and activated by 
enteropeptidases in the duodenum, generating 
trypsin that activates the other proteases in a 
cascade. Pancreatic tissue is protected against 
autodigestion by the following: 
• Storing the enzymes as inactive zymogen 
• Restricting protease activation to the 
duodenum
• Trypsin inhibitor, which is copackaged in the 
secretory granules with trypsinogen
• The higher pH in the acini and duct system due 
to HCO3− secreted by the centroacinar and 
intercalated duct cells, which helps keep all the 
enzymes inactiveRegulation of exocrine pancreatic 
secretion
• Mainly through two polypeptide hormones 
produced by enteroendocrine cells of the small 
intestine in response to fatty acids & proteins: 
1. Cholecystokinin (CCK) stimulates enzyme secretion 
by the acinar cells. 
2. Secretin stimulate HCO3− secretion by the duct 
cells, reduces concentration of H ions & raising PH 
optimal for digestion
• Autonomic (parasympathetic) nerve fibers also 
stimulate secretion from both acinar and duct cells.Medical application 
• Pancreatic cancer, which is usually a carcinoma of duct 
cells, can arise anywhere in the gland but occurs most 
often in the head of the organ near the duodenum. The 
tumor is usually asymptomatic until growth and metastasis 
are well advanced, leading to the low rate of early 
detection and subsequent high rate of mortality. 
• In acute pancreatitis, the proenzymes may be activated 
and digest pancreatic tissues, leading to very serious 
complications. Possible causes include infection, gallstones, 
alcoholism, drugs, and trauma. Chronic pancreatitis can 
produce progressive fibrosis and loss of pancreatic 
function. Liver 
• The liver is the largest internal organ, in adults averaging 
about 1.5 kg or 2% of the body weight.
• Located in the right upper quadrant of the abdomen just 
below the diaphragm 
• Has major left and right lobes with two smaller inferior 
lobes, 
• most of which are covered by a thin capsule 
(Glisson'scapsule )and mesothelium of the visceral 
peritoneum
• The capsule thickens at the hilum (or porta hepatis) on the 
inferior side, where the dual blood supply from the hepatic 
portal vein and hepatic artery enters the organ and where 
the hepatic vein, lymphatics, and common hepatic (bile) 
duct exit.Blood supply to the liver 
(hepatic circulation)Function of the liver
• The main digestive function of the liver is production of 
bile, a complex substance required for the emulsification, 
hydrolysis, and uptake of fats in the duodenum. 
• The liver is also the major interface between the digestive 
system and the blood, as the organ in which nutrients 
absorbed in the small intestine are processed before 
distribution throughout the body. 
• About 75% of the blood entering the liver is nutrient-rich 
(but O2-poor) blood from the portal vein arising from the 
stomach, intestines, and spleen; the other 25% comes 
from the hepatic artery and supplies the organ’s O2.• In addition to secretion of bile components, 
hepatocytes and other liver cells process the 
contents of blood, with many specific functions:
• Synthesis and secretion of the major plasma 
proteins, including albumins, fibrinogen, 
apolipoproteins, transferrin, and many others
• Production of angiotensinogen important for salt 
conserving (renin-angiotensin-aldosterone 
system)
• Breakdown (detoxification) and conjugation of 
ingested toxins, including many drugs
• Amino acid deamination, producing urea 
removed from blood in kidneys• Conversion of amino acids into glucose 
(gluconeogenesis)
• Storage of glucose in glycogen granules and 
triglycerides in small lipid droplets
• Storage of vitamin A (in hepatic stellate cells) 
and other fat-soluble vitamins 
• Removal of effete erythrocytes (by specialized 
macrophages, or Kupffer cells)
• Storage of iron in complexes with the protein 
ferritin. • Activation of vitamin D to 25,hydroxy D3(calcidiol) 
by 25,hydoxlase enzyme 
• calcidiol converted to calcitriol ( 1,25,hydroxy D3) 
in kidney by 1α hydroylase
• Secret hormones : thrombopointin , hipicidin
• Secret cholesterol and bilirubin Structure and function of liver
• Abundant rough ER is focused on synthesis of plasma 
proteins and causes cytoplasmic basophilia
• Abundant smooth ER, contains the enzyme systems 
for the inactivation or detoxification of substances in 
blood, which are then usually excreted with bile.
• These include enzymes responsible for oxidation,
methylation, and conjugation of steroids, 
barbiturates, antihistamines, and other drugs.
• Other SER enzymes (glucuronosyl transferases) 
conjugate bilirubin to glucuronate, rendering it more 
soluble and facilitating its excretion in bile• Glycogen granules and small lipid droplets in 
hepatocytes, and very small electron-dense ferritin 
complexes (hemosiderin) primarily in the Kupffer cells, 
respectively mediate temporary storage of glucose, 
triglycerides, and iron.
• Liver glycogen is depot of glucose and is mobilized if blood 
glucose falls bellow normal
• Hepatocyte peroxisomes are also abundant and 
important for oxidation of excess fatty acids and 
conversion of excess purines to uric acid
• Many Golgi complexes are also present, involved in 
synthesis of both plasma proteins and bile components. 
• The numerous mitochondria provide energy for all these 
activities Hepatocytes & Hepatic Lobules 
• Hepatocytes are large cuboidal or polyhedral epithelial 
cells, with large, round central nuclei and eosinophilic
cytoplasm rich in mitochondria. 
• The cells are frequently binucleated and about 50% of 
them are polyploid, with two to eight times the normal 
chromosome number
• The liver parenchyma is organized as thousands of 
small (~0.7 × 2 mm) hepatic lobules in which 
hepatocytes form hundreds of irregular plates 
arranged radially around a small central vein 
• The hepatocyte plates are supported by a delicate 
stroma of reticulin fibershepatic lobules are polygonal units 
showing plates of epithelial cells 
called hepatocytes radiating from a 
central venule (C).
(b) peripheral CT of portal areas 
contains the portal triad: small bile 
ductules (D), venule (V) branches 
of the portal vein, and arteriole (A) 
branches of the hepatic artery.(a) Hepatocytes (H) are polygonal 
epithelial cells, which form 
branching, irregular plates 
separated by venous sinusoids (S)
Reticulin (collagen type III) fibers 
(R) running along the plates of 
hepatocytes (H) Most CT in the 
liver is found in the septa and 
portal tractsPortal area
• Peripherally each lobule has 3 to 6 portal areas 
with more fibrous CT, each of which contains 3 
interlobular structures that comprise the portal 
triad:
• A venule branch of the portal vein, with blood rich 
in nutrients but low in O2.
• An arteriole branch of the hepatic artery, which 
supplies O2.
• One or two small bile ductules of cuboidal 
epithelium, branches of the bile conducting system.
• Most of the peripheral portal areas also contain 
lymphatics and nerve fibersMedical application
• In the normal liver most dense connective tissue 
is found only in the portal areas, surrounding the 
blood vessels and bile ductule. 
• In liver cirrhosis, which occurs late in chronic 
liver disease, fibrosis and proliferation of 
fibroblasts and hepatic stellate cells occur beyond 
the portal areas. The excessive connective tissue 
may disrupt the normal hepatic architecture and 
interfere with liver functionvascular sinusoids
• Between all of the anastomosing 
plates of hepatocytes of a hepatic 
lobule 
• Emerge from the peripheral branches 
of the portal vein and hepatic artery 
and converge on the lobule’s central 
vein
• The venous and arterial blood mixes in 
these irregular hepatic sinusoids
• The anastomosing sinusoids have 
thin, discontinuous linings of 
fenestrated endothelial cells 
surrounded by sparse basal lamina 
and reticular fibersSpace of Disse
• The discontinuities and fenestrations allow plasma to 
fill a narrow perisinusoidal space (or space of Disse) 
and directly bathe the many irregular microvilli 
projecting from the hepatocytes into this space 
• This direct contact between hepatocytes and plasma 
facilitates most key hepatocyte functions involving 
uptake and release of nutrients, proteins, and 
potential toxins
• The fenestrae and discontinuity of endothelium allow 
the free flow of plasma but not of cellular elements 
into the space of DisseOther cells 
• are found with the sinusoids of hepatic lobules:
1. stellate macrophages, usually called Kupffer
cells, are found on the luminal surface of the 
endothelial cells, within the sinusoids 
• These cells recognize and phagocytose aged 
erythrocytes, freeing heme and iron for reuse or 
storage in ferritin complexes
• Kupffer cells are also antigen-presenting cells and 
remove any bacteria or debris present in the 
portal blood2. Hepatic stellate cells (or Ito cells) are found In the 
perisinusoidal space have small lipid droplets, which store 
vitamin A and other fat-soluble vitamins 
These mesenchymal cells, which are difficult to see in 
routine preparations, also produce extracellular matrix 
(ECM) components (becoming myofibroblasts after liver 
injury) and produce cytokines that help regulate Kupffer
cell activityBlood circulation in liver
• The endothelium of the central vein in the middle of 
each hepatic lobule is supported by a very thin layer 
of fibrous CT
• Central venules from each lobule converge into 
larger veins, which eventually form two or more large 
hepatic veins that empty into the inferior vena cava. 
• Blood always flows from the periphery to the center 
of each hepatic lobule. 
• Consequently, oxygen and metabolites, as well as all 
other toxic or nontoxic substances absorbed in the 
intestines, reach the lobule’s peripheral cells first and 
then the more central cells. Bile secretion
• The smaller apical surfaces of the hepatocytes form bile 
canaliculi and are involved in exocrine secretion of bile 
• Hepatocytes adhere firmly with desmosomes and junctional
complexes. 
• The apical surfaces of two adherent hepatocytes are 
grooved and juxtaposed to form the canaliculus, sealed by 
tight junctions, into which bile components are secreted 
• These canaliculi are elongated spaces with large surface 
areas due to the many short microvilli from the constituent 
hepatocytes
• The bile canaliculi form a complex anastomosing network of 
channels through the hepatocyte plates that end near the 
portal tracts• The bile flow therefore progresses in a direction 
opposite to that of the blood, that is, from the 
center of the lobule to its periphery
• Bile canaliculi are the smallest branches of the 
biliary tree or bile conducting system
• They empty into bile canals of Hering composed of 
cuboidal epithelial cells called cholangiocytes
• The short bile canals quickly merge in the portal 
areas with the bile ductules lined by cuboidal or 
columnar cholangiocytes and with a distinct CT 
sheath. 
• Bile ductules gradually merge, enlarge, and form 
right and left hepatic ducts leaving the liver.Near the periphery of each hepatic lobule, many bile canaliculi
join with the much larger bile canals of Hering, which are lined 
by cuboidal epithelial cells called cholangiocytes. These canals 
soon join the bile ductules in the portal areas and drain into the 
biliary tree.• Into the canaliculi hepatocytes continuously 
secrete bile, a mixture of :
• bile acids (organic acids such as cholic acid)
• bile salts (the deprotonated forms of bile acids), 
• electrolytes, fatty acids, phospholipids, 
cholesterol, and bilirubin
• Some bile components are synthesized in 
hepatocyte SER, but most are taken up from the 
perisinusoidal space
• all are quickly secreted into the bile canaliculi• Bile acids/salts have an important function in 
emulsifying the lipids in the duodenum, promoting 
their digestion and absorption. 
• Bilirubin is a pigmented breakdown product of heme
that is released from splenic macrophages primarily, 
but also from Kupffer cells, and carried to 
hepatocytes bound to albumen. Released into the 
duodenum with bile, bilirubin is converted by 
intestinal bacteria into other pigmented products, 
some of which are absorbed in the intestinal mucosa 
to be processed and excreted again in the liver or 
excreted into urine by the kidneys. These bilirubinrelated compounds give feces and urine their 
characteristic colors.Medical application
• An important function of hepatocyte SER is the 
conjugation of hydrophobic (water-insoluble), yellow 
bilirubin by glucuronosyl transferases to form watersoluble, nontoxic bilirubin glucuronide, which is 
excreted into the bile canaliculi. When bilirubin 
glucuronide is not formed or excreted properly, various 
diseases characterized by jaundice can result.
• A frequent cause of jaundice in newborns is an 
underdeveloped state of the hepatocyte SER (neonatal 
hyperbilirubinemia). 
• A treatment in these cases is exposure to blue light from 
ordinary fluorescent tubes, which transforms 
unconjugated bilirubin into a water-soluble 
photoisomer that can be excreted by the kidneys.(1) RER is primarily engaged 
in synthesis of plasma 
proteins for release into the 
perisinusoidal space. 
(2) Potentially toxic 
compounds, bilirubin 
(bound to albumin) and bile 
acids are taken up from the 
perisinusoidal space, 
processed by enzymes in the 
tubulovesicular system of 
the SER, and secreted into 
the bile canaliculi.
(3) Glucose is taken up from 
the perisinusoidal space and 
stored in glycogen granules, 
with the process reversed 
when glucose is needed.Hepatic lobules
1. The classic hepatic lobule with blood flowing past 
hepatocytes from the portal areas to a central venule, 
emphasizes the endocrine function of the structure 
producing factors for uptake by plasma. 
2. The concept of portal lobules of hepatocytes is more 
useful when considering the exocrine function of these 
cells, that is, bile secretion 
• The portal area has the bile ductule at the center, and 
bile, moving in the opposite direction as the blood, 
flows toward it from all the surrounding hepatocytes 
• The tissue draining bile into each portal area duct is 
roughly triangular in shape, with the central veins of 
three classic lobules at its angles3. The hepatic acinus, a third way of viewing liver 
cells, emphasizes the nature of the blood supply to 
the hepatocytes and the oxygen gradient from the 
hepatic artery branch to the central vein
• In a liver acinus hepatocytes make up an irregular 
oval or diamond-shaped area extending from two 
portal triads to the two closest central veins 
• The direction of blood flow partly explains why the 
properties and function of the periportal
hepatocytes differ from those of the centrolobular
cells • Periportal hepatocytes, comprising zone I in the 
acinus, get the most oxygen and nutrients and can 
most readily carry out functions requiring 
oxidative metabolism such as protein synthesis. 
• Hepatocytes in zone III, near the central vein, get 
the least oxygen and nutrients. They are the 
preferential sites of glycolysis, lipid formation, and 
drug biotransformations and are the first 
hepatocytes to undergo fatty accumulation and 
ischemic necrosis
• In the intervening zone II, hepatocytes have an 
intermediate range of metabolic functions 
between those in zones I and IIIConcepts of structure-function relationships in liverLiver regeneration
• Unlike the salivary glands and pancreas, the liver has 
a strong capacity for regeneration despite its normal 
slow rate of cell renewal. 
• Hepatocyte loss from the action of toxic substances 
triggers mitosis in the remaining healthy hepatocytes 
in a process of compensatory hyperplasia that 
maintains the original tissue mass. 
• Surgical removal of a liver portion produces a similar 
response in the hepatocytes of the remaining lobe 
• The regenerated liver tissue is usually well organized, 
with the typical lobular arrangement, and replaces 
the functions of the destroyed tissue. • This regenerative capacity is important clinically 
because one major liver lobe can sometimes be 
donated by a living relative for surgical transplant 
and full liver function restored in both donor and 
recipient.
• Besides proliferation of existing hepatocytes, a role 
for liver stem cells in regeneration has been shown 
in some experimental models. Such cells, often 
called oval cells, are present among cholangiocytes
of the bile canals near portal areas and produce 
progenitor cells for both hepatocytes and 
cholangiocytes.• Liver regeneration following partial hepatectomy occurs 
in three phases including :
• (a) initiation or priming phase 
• (b) proliferation phase
• (c) termination phase• Priming phase occurs within 5 hours of hepatectomy
and involves activation and over expression of multiple 
specific genes to prepare the hepatocytes for 
replication. The regulatory mechanisms prepare 
hepatocytes to enter the cell cycle.
• The proliferation phase involves activation of various 
growth factors, During this phase, hepatocytes undergo 
a series of cell division cycles and expansion
•
]Termination phase is coordinated by TGF-β 
(transforming growth factor beta) that is responsible for 
stopping the regenerative process and preventing liver 
overgrowthMedical application
• Fatty liver disease is a reversible condition in 
which large lipid droplets containing triglycerides 
accumulate abnormally in hepatocytes via the 
process called steatosis (fat buildup).
• This disorder has multiple causes, but it occurs 
most commonly in individuals with alcoholism or 
obesity. Accumulation of fat in hepatocytes may 
produce a progressive inflammation of the liver, 
or hepatitis, in this case called steatohepatitisBiliary tree and gall bladder
• The bile produced by the hepatocytes flows 
through the bile canaliculi, bile ductules, and 
bile ducts. These structures gradually merge, 
forming a converging network that ultimately 
forms the common hepatic duct, which joins 
the cystic duct from the gallbladder and 
continues to the duodenum as the common 
bile duct• The hepatic, cystic, and common bile ducts are 
lined with a mucous membrane having a simple 
columnar epithelium of cholangiocytes.
• The lamina propria and submucosa are relatively 
thin, with mucous glands in some areas of the 
cystic duct, and surrounded by a thin muscularis
• This muscle layer becomes thicker near the 
duodenum and finally, in the duodenal papilla, 
forms a sphincter of Oddi that regulates bile flow 
into the small bowelGall bladder
• The gallbladder is a hollow, pear-shaped organ
• capable of storing 30-50 mL of bile that is 
concentrated during storage.
• The wall of the gallbladder consists of :
• a mucosa composed of simple columnar 
epithelium and lamina propria, a thin muscularis
with bundles of muscle fibers oriented in several 
directions, and an external adventitia or serosa 
• The mucosa has numerous folds that are 
particularly evident when the gallbladder is 
emptyThe gallbladder is a saclike 
structure that stores and 
concentrates bile, and releases it 
into the duodenum after a meal.
(a) Its wall consists largely of a 
highly folded mucosa, with a 
simple columnar epithelium 
(arrows) overlying a typical lamina 
propria (LP); a muscularis (M) with 
bundles of muscle fibers oriented 
in all directions to facilitate 
emptying of the organ; and an 
external adventitia (A) where it is 
against the liver and a serosa 
where it is exposedUltra structure of epithelial cells 
• The lining epithelial cells of the gallbladder are 
active transport have prominent mitochondria, 
microvilli, and large intercellular spaces 
• Actively transporting water, for concentrating 
bile 
• The mechanism for this includes activity of Na+ 
pumps in the basolateral membranes, followed 
by passive movement of water from the bile.
•Release of bile 
• To move stored bile into the duodenum, 
contraction of the gallbladder muscularis is induced 
by cholecystokinin (CCK) released from 
enteroendocrine cells of the small intestine. 
• Release of CCK is, in turn, stimulated by the 
presence of ingested fats in the small intestine. 
• Gallbladder removal due to obstruction or chronic 
inflammation leads to the direct flow of bile from 
liver to gut, with few major consequences on 
digestion. Medical application
• Reabsorption of water from bile in the gallbladder is involved in the 
formation of gallstones in the lumen of the gallbladder or biliary 
ducts, a condition called cholelithiasis
• This disorder usually originates with bile that already contains 
excessive amounts of normal bile components. 
• Supersaturation of cholesterol in bile can lead to the formation of 
cholesterol stones, the most common form
• Brown or black pigment stones can form when bile contains 
excessive amounts of unconjugated bilirubin, which can result from 
chronic hemolysis associated with disorders such as sickle cell 
anemia
• Gallstones can lead to biliary obstruction or more commonly to 
inflammation in acute or chronic cholecystitis