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Liver and Pancreas
- Liver
Lobule and portal area (triad)
Hepatic acinus
Bile duct and galebladder
Functions of the liver
- Pancreas
+ Definitions
+ Lobule and acinus
+ Pancreatic duct system
+ Islets
+ Functions of the pancreas
- Objectives
- Liver
Lobule and portal area (triad)
Hepatic acinus
Bile duct and galebladder
Functions of the liver
- Pancreas
+ Definitions
+ Lobule and acinus
+ Pancreatic duct system
+ Islets
+ Functions of the pancreas
- Objectives
- All nutrients and liquids absorbed in the intestines enter the
liver through the hepatic portal vein
- Absorbed products first go through liver capillaries called
- Nutrient-rich blood in the hepatic portal vein first brought to
the liver before it enters general circulation
- However, venous blood from digestive organs in hepatic
portal vein poor in oxygen
- Consequence: hepatic artery from aorta supplies liver cells
with oxygenated blood, giving dual blood supply to the liver
- Liver exhibits hexagonal units called liver (hepatic) lobules
- In the center of each lobule: central vein
- Plates of liver cells, hepatocytes, and sinusoids radiate
from central vein to periphery, where, branches of hepatic
artery, hepatic portal vein, bile duct and lymph vessels
form portal areas or triads in connective tissue
- In human liver, 3 to 6 portal areas can be seen per lobule
- The liver is bounded by a connective tissue capsule which extends into its
substance as highly branched septae. The afferent blood vessels and lymphatics
follow this connective tissue highway throughout the liver. Efferent vessels
traverse a route separate from connective tissue scaffolding
Capsule and septae are stained blue ,
while hepatocytes are magenta
(Masson’s trichrome). The connective
tissue septae invaginating from the
capsule delineate hepatic lobules, the
structural unit of the liver
CV: central vein; *: pa: portal area
Lobules of the liver (primate)
- The connective tissue septae invaginating from the capsule delineate
hepatic lobules, the structural unit of the liver
- A lobule is a roughly hexagonal arrangement of plates of hepatocytes
radiating outward from a central vein (CV) in the center
- At the vertices of the lobule are regularly distributed portal triads (also
known as portal areas). Examination of a triad in cross section reveal a bile
duct and branches of the hepatic artery and hepatic portal vein
cv: central vein; pa: portal area
bd: bile duct; v: branch of hepatic portal
vein; a: branch of hepatic artery
Liver lobule- Portal area (triad)
Due to plane of section, one can often observe more than one of each of
these structures in a given triad or absence of one or more structures
Lobules are almost impossible to miss in some species, but one should
also be able to recognize them in other species. The precise boundaries
of lobules are sometimes difficult to discern
- Venous and arterial blood from peripheral areas first mix in the
liver sinusoids as it flows towards the central vein
- From here, blood enters the general circulation through the
hepatic veins that leave the liver and enter the inferior vena cava
Hepatic acinus
The lobule is the structural unit of the liver and rather easy to observe
In contrast, the hepatic acinus is more difficult to visualize, but represents a unit that
is of more relevance to hepatic function because it is oriented around the afferent
vascular system
The acinus consists of an irregular shaped, roughly ellipsoidal mass of hepatocytes
aligned around the hepatic arterioles and portal venules just as they anastomose into
The acinus is roughly divided into zones that correspond to distance from the arterial
blood supply - those hepatocytes closest to the arterioles (zone 1) are the best
oxygenated, while those farthest from the arterioles have the poorest supply of
oxygen. This arrangement also means that cells in the center of the acinus (zone 1)
are the first to "see" and potentially absorb blood-borne toxins absorbed into portal
blood from the small intestine
- The parenchymal cells of the liver are hepatocytes. Roughly 80%
of the mass of the liver is contributed by hepatocytes
- These polygonal cells are joined to one another in anastomosing
plates, with borders that face either the sinusoids (sinusoidal
face) or adjacent hepatocytes (lateral faces)
- A portion of the lateral faces is modified to form bile canaliculi.
Microvilli are present abundantly on the sinusoidal face and
project sparsely into bile canaliculi
- Hepatocytes are the chief functional cells of the liver and perform
an astonishing number of metabolic, endocrine and secretory
functions. The ultrastructure appearance of hepatocytes reflects
their function as metabolic superstars, with abundant rough and
smooth endoplasmic reticulum, and Golgi membranes
- Glycogen granules and vesicles containing very low density
lipoproteins are seen
- Hepatocyte nuclei are distinctly round, with one or two prominent nucleoli. A
majority of cells have a single nucleus, but binucleated cells are common
- Hepatocytes are exceptionally active in synthesis of proteins and lipids for
export. As a consequence of these activities, examination of hepatocytes reveals
bountiful quantities of both rough and smooth endoplasmic reticulum
- Hepatocytes typically contain many stacks of Golgi membranes. Golgi vesicles
are particularly numerous in the vicinity of the bile canaliculi, reflecting transport
of bile constituents into those channels
- Another important function of hepatocytes is to synthesize and secrete very low
density lipoproteins
- Another type of particle observed in copious quantities in liver is glycogen.
Glycogen is a polymer of glucose and the density of glycogen aggregates in
hepatocytes varies dramatically depending on whether the liver is examined
shortly after a meal (abundant glycogen) or following a prolonged fast (minimal
quantities of glycogen)
(Electron microscopy)
When stained with using the
periodic acid-Schiff (PAS)
technique, glycogen stains
bright pink in color. Left panel:
mouse that fasted overnight and
thus had very low levels of
glycogen in liver. Right panel: from
mouse that stuffed himself on
mouse chow 2 hours prior to fixing
the liver, and thus had high levels
of hepatic glycogen. These
accumulations are seen as pink
areas of PAS-positive material
throughout the section
Glycogen granules in liver cells (PAS staining)
- Hepatocytes make contact with blood in sinusoids: distensible vascular channels
lined with highly fenestrated endothelial cells and populated with
phagocytic Kupffer cells. The space between endothelium and hepatocytes is
called the Space of Disse which collects lymph for delivery to lymphatic capillaries
- Sinusoids are low pressure vascular channels that receive blood from terminal
branches of the hepatic artery and portal vein at the periphery of lobules and
deliver it into central veins. Sinusoids are lined with endothelial cells and flanked
by plates of hepatocytes
Blood cells
The space between sinusoidal endothelium and hepatocytes is called
the space of Disse. Sinusoidal endothelial cells are highly fenestrated, which
allows virtually unimpeded flow of plasma from sinusoidal blood into the
space of Disse. This arrangement has at least two important consequences:
+ Hepatocytes are bathed in plasma derived in large part from venous blood
returning from the small intestine. Following meals, that plasma is nutrient-rich
+ Plasma which collects in the space of Disse flows back toward the portal
tracts, collecting in lymphatic vessels and forming a large fraction of the body's
en: Endothelial cells
cv: Central vein
H: Hepatocyte
K: Kuppfer cell
S: Sinusoid
- Another important feature of hepatic sinusoids is that they house an important
part of the phagocytic system. Sinusoids are populated by numerous Kupffer
cells, a type of fixed macrophage. Identifying Kupffer cells in conventionallystained sections of liver is not easy. However, they stand out sharply when full
of phagocytosed ink particles. They can be immunostained by different markers
Kuppfer cells (H&E)
Kuppfer cells (immunostained for CD68)
Kuppfer cells in a liver lobule (india ink preparation)
- Hepatocytes secrete bile into tiny channels called bile canaliculi located between
- Bile originates as secretions from the basal surface of hepatocytes, which
collect in channels called canaliculi. Canaliculi converge at the periphery
of lobules into the portal area as bile ducts. The bile ducts drain into larger hepatic
ducts that carry bile out of the liver
- By contrast, blood flows in the sinusoids toward the central vein. As a result,
bile and blood do not mix
Bile canaliculi in liver lobule (osmic acid staining)
Reticular fibers
Supporting connective tissue: fine reticular fibers made of collagen type III
Reticular fibers line sinusoids, support endothelial cells and form dense
network of reticular fibers in wall of central vein
Merge with collagen fibers in interlobular septum where they surround portal vein
and bile duct
Reticular fibers in liver lobule (reticulin method)
Bile duct and gallbladder
- Bile flows out of the liver through hepatic ducts, which join and extend as the
common bile duct (also known as the bile duct) to traverse the wall of the
duodenum and deliver bile into its lumen. In species with a gallbladder, the
hepatic ducts join with the cystic duct, which conveys bile to and from the gall
- The gallbladder is a distensible sac and, when not distended, its mucosa is
thrown into many folds. The lumen of the gallbladder is lined with a high
columnar epithelium. The connective tissue wall contains abundant elastic fibers
and layers of smooth muscle
Wall of gallbladder
Exocrine functions of the liver
- Liver synthesizes and releases bile into bile canaliculi. Bile flow
regulated by hormones such as cholecystokinin (CCK). Stimulated
when dietary fats in the chyme enter the duodenum. CCK causes
contraction of smooth muscles in gallbladder, allowing bile to
enter duodenum
- Bile salts emulsify fats in the duodenum allowing more efficient
digestion of fats by the fat-digesting pancreatic lipases
- Hepatocytes excrete bilirubin, a toxic chemical formed in the
body after degradation of worn-out erythrocytes by liver
macrophages, Kuppfer cells. Bilirubin is taken up by hepatocytes
from the blood and excreted into bile
- Hepatocytes have role in immune system. Antibodies produced by
plasma cells in the intestinal lamina propria are taken from blood
by hepatocytes and transported into bile canaliculi and bile. From
here, antibodies enter the intestinal lumen where they control the
intestinal bacterial flora
Endocrine functions of the liver
- Hepatocytes are also endocrine cells
- They synthesize numerous plasma proteins, including albumin
and the blood-clotting factors prothrombin and fibrinogen
- Liver stores fats, vitamins, carbohydrates as glycogen
- When the cells need glucose, glycogen stored in the liver is
converted into glucose and released in the bloodstream
- Hepatocytes also detoxify blood of drugs and harmful
- Kupffer cells are specialized liver phagocytes derived from blood
monocytes. They filter and phagocytose particulate material,
cellular debris and damaged erythrocytes
- Liver performs vital functions in life: in the fetus, the liver is
the site of hematopoiesis
Section of liver taken from a 100 day sheep fetus. The clusters of cells
in sinusoids are various types of basophilic immature blood cells. In the fetus,
the liver is a major site of hematopoiesis, or formation of blood cells. Hepatic
hematopoiesis is not normally seen after birth, although it can occur under
certain pathologic conditions
- Liver
Lobule and portal area (triad)
Hepatic acinus
Bile duct and galebladder
Functions of the liver
- Pancreas
+ Definitions
+ Lobule and acinus
+ Pancreatic duct system
+ Islets
+ Functions of the pancreas
- Objectives
- Most of the pancreas is an exocrine gland
- Exocrine secretory units, or acini, contain pyramidal-shaped acinar
or zymogenic cells. Serous acini: well stained acini on HE
- Each cell of acini has its apex filled with secretory granules
- Granules contain the precursors of several pancreatic digestive
enzymes secreted into the excretory ducts in an inactive form
- Secretory acini subdivided into lobules and bound together by
loose connective tissue
- Excretory ducts start from within the center of individual acini
(pale-staining centro-acinar cells), and continue into short
intercalated ducts
- Intercalated ducts merge in intralobular ducts, forming then
interlobular ducts that empty into main pancreatic duct
- Endocrine units of the pancreas are scattered among the exocrine
acini as isolated, pale staining vascularized units called pancreatic
islets (of Langerhans)
- Four cell types can be identified by immunocytochemistry in each
islet: alpha, beta, delta and pancreatic polypeptide (PP) cells
- Alpha cells constitue 20% of the islets and located primilarly at
the periphery of islets. Produce glucagon
- Beta cells are more numerous (70% of the islets) and located in
center of islets. Produce insulin
- Remaining cells are few in number and located in various places.
Delta cells produce somatostatin. Pancreatic polypeptide cells
(PP) produce pancreatic polypeptide, which inhibits production
of pancreatic enzymes and alkaline secretions
The pancreas is surrounded by a very thin connective tissue capsule that
invaginates into the gland to form septae, which serve as scaffolding for large
blood vessels. Further, these septae divide the pancreas into distinctive lobules
Exocrine and endocrine pancreas
- The exocrine pancreas is classified as a compound tubuloacinous gland. The
cells that synthesize and secrete digestive enzymes are arranged in grape-like
clusters called acini, very similar to what is seen in salivary glands
Centro-acinar cell
Centroacinar cells: excretory duct of each individual acinus. Continuous with
epithelium of intercalated ducts
Pancreatic duct system
Intralobular duct
Intercalated duct
(low cuboidal, almost squamous
(intercalated duct emptying in
cuboidal intralobular duct)
Small interlobular duct
Large interlobular duct
(columnar epithelium)
A: Artery; V: vein: D: intralobular duct
The endocrine cells within islets are arranged as irregular cords around
abundant capillaries, which receive the secreted hormones for delivery into the
systemic circulation
1: acini; 2: islets; 3: interlobular
connective tissue; 4: vessel
1: acini; 2: islets; 3: intralobular duct;
4: interlobular connective tissue
Pancreas: endocrine (pancreatic islet) and exocrine regions
Pancreatic islet
Pancreaticp islet (Gomori’s chrome alum hematoxylin and phloxine
Functional correlations: exocrine pancreas
Pancreas produces numerous digestive enzymes that exit the gland
through major excretory duct
Both hormones and vagal stimulation regulate pancreatic exocrine
- Two intestinal hormones, secretin and cholecystokinin (CCK) secreted by
cells (APUD) cells in the duodenum mucosa into the
bloodstream regulate pancreatic secretions
Acidic chyme in duodenum induces release of secretin. Secretin triggers
exocrine pancreas to produce watery fluid rich in sodium bicarbonate ions
(role: to neutralize acidic chyme, stop action of pepsin in stomach, create a
neutral pH in duodenum)
Fats and proteins in duodenum induce release of CCK into bloodstream.
CCK stimulates acinar cells to secrete large amounts of pancreatic amylase
for carbohydrate digestion, pancreatic lipase for lipid digestion,
deoxyribonuclease and ribonuclease for digestion of nucleic acids,
proteolytic enzymes trypsinogen, chymotrypsinogen
Pancreatic enzymes are first produced in acinar cells in an inactive form
then activated in the duodenum by the hormone enterokinase secreted by
intestinal mucosa. This hormone converts trypsinogen into trypsin which
then converts all other pancreatic enzymes into active digestive enzymes
Functional correlations: endocrine pancreas
+ Alpha cells produce the hormone glucagon. Released in response
to low levels of glucose in the blood. Glucagon elevates blood
glucose levels by accelerating the conversion of glycogen, amino
acids and fatty acids in the hepatocytes into glucose
+ Beta cells produce insulin. Release stimulated by elevated blood
glucose levels after a meal. Insulin lowers blood glucose levels by
accelerating membrane transport of glucose into hepatocytes,
muscle cells and adipose cells. Accelerates the conversion of glucose
into glycogen in hepatocytes. Effects of insulin on blood glucose
levels are opposite to the ones of glucagon
+ Delta cells secrete the hormone somatostatin. Decreases and
inhibits secretory activities of both alpha (glucagon-secreting) and
beta (insulin-secreting) cells through local action within the
pancreatic islets
+ Pancreatic polypeptide cells (PP) produce the pancreatic
polypeptide which inhibits production of pancreatic enzymes and
alkaline secretions
- Liver
Lobule and portal area (triad)
Hepatic acinus
Bile duct and galebladder
Functions of the liver
- Pancreas
+ Definitions
+ Lobule and acinus
+ Pancreatic duct system
+ Islets
+ Functions of the pancreas
- Objectives
To know the architecture of the liver (lobule, triad, hepatic acinus, hepatocyte,
To know functional correlations of the liver
To know the architecture of the pancreas exocrine (lobules, acini) and
endocrine (islets)
To know pancreatic ducts
To know functional correlations of the pancreas