Ingegneria delle tecnologie per la salute
Fondamenti di anatomia e istologia
aa. 2019-20
Lesson 7. Digestive system and peritoneum
Liver • hepatic artery delivers
oxygenated blood from heart to liver, hepatic portal vein delivers partially deoxygenated blood containing nutrients (+ drugs and toxins) absorbed from the small intestine and actually supplies more oxygen to liver than do much smaller hepatic arteries; after processing bloodborne nutrients and toxins, liver releases nutrients needed by other cells back into the blood, which drains into central vein and then through hepatic vein to inferior vena cava.
• hepatic portal circulation = all blood from alimentary canal passes through liver (explaining liver most common site for alimentary canal cancers metastasis)
Liver: Histology 1 hepatocytes [liver’s main cell type, accounting for around 80% of liver's volume, playing a role in a wide variety of secretory, metabolic, and endocrine functions; plates of hepatocytes called hepatic laminae radiate outward from portal vein in each hepatic lobule] = from their central position, hepatocytes process nutrients, toxins, and waste materials carried by blood: materials such as bilirubin processed and excreted into bile canaliculi, other materials including proteins, lipids, and carbohydrates processed and secreted into sinusoids or just stored in cells until called upon.
= 3 main components:
Liver: Histology 2 bile canaliculi [grooves in cell membranes between adjacent hepatocytes accumulating bile produced by hepatocytes: from here, bile flows first into bile ductules and then into bile ducts, uniting to form larger right and left hepatic ducts, which themselves merge and exit liver as common hepatic duct, that joins with cystic duct from gallbladder, forming common bile duct through which bile flows into small intestine]
= 3 main components:
Liver: Histology
3 hepatic sinusoids [open, porous blood space formed by fenestrated capillaries from nutrient-rich hepatic portal veins and oxygen-rich hepatic arteries, where hepatocytes are tightly packed around, giving them easy access to the blood] = combine and send blood to a central vein and then through hepatic vein into inferior vena cava (this means that blood and bile flow in opposite directions); also contain star-shaped reticuloendothelial cells (Kupffer cells), phagocytes removing dead red and white blood cells, bacteria, and other foreign material that enter sinusoids
= 3 main components:
Liver: Histology
Liver: Histology
Liver: Histology
Liver: Histology
Liver: Histology portal triad = distinctive arrangement around perimeter of hepatic lobules, consisting of 3 basic structures: a bile duct, a hepatic artery branch, and a hepatic portal vein branch.
Liver: Histology portal triad
Liver: Histology portal triad
Blood flow
Bile flow
Liver: Histology
Liver: Histology
Liver: Histology
Liver: Histology
Liver: Histology
Liver: Histology
Liver: Histology
Liver: Histology
Liver: Histology
Liver: Bile • lipids are hydrophobic (= do not dissolve in water), before they can be digested in watery
environment of small intestine, large lipid globules must be broken down into smaller lipid
globules (= emulsification)
• Bile = yellow-brown or yellow-green alkaline solution (pH 7.6 to 8.6) mixture of water, bile salts, bile pigments, phospholipids (such as lecithin), electrolytes, cholesterol, and triglycerides secreted (about liter each day) by liver to accomplish emulsification of lipids in small intestine.
• bile salts and phospholipids = components most critical to emulsification having a nonpolar (hydrophobic) region as well as a polar (hydrophilic) region [hydrophobic region interacts with large lipid molecules, whereas hydrophilic region interacts with watery chyme in intestine: large lipid globules being pulled apart into many tiny lipid fragments of about 1 μm , dramatically increasing surface area available for lipid-digesting enzyme activity]
Liver: Bile • While most constituents of bile are
eliminated in feces, bile salts are reclaimed by enterohepatic circulation: once bile salts reach ileum, they are absorbed and returned to liver in hepatic portal blood; hepatocytes then excrete bile salts into newly formed bile.
• bilirubin = main bile pigment [waste product produced when spleen removes old or damaged red blood cells from circulation, including proteins, iron, and toxic bilirubin, transported to liver via splenic vein of hepatic portal system: proteins and iron recycled, whereas bilirubin excreted in bile, accounting for green color of bile, and transformed by intestinal bacteria into stercobilin (= brown pigment giving stool its characteristic color: in some disease states, bile does not enter intestine, resulting in white (‘acholic’) stool with a high fat content, since virtually no fats are broken down or absorbed)]
Liver: Bile • Hepatocytes work non-stop, but bile production increases when fatty chyme enters
duodenum and stimulates secretion of gut hormone secretin. Between meals, bile is produced but conserved. The valve-like hepatopancreatic ampulla closes, allowing bile to divert to gallbladder, where it is concentrated and stored until next meal.
Liver & Pancreas
Pancreas
= soft, oblong, glandular organ lying transversely in retroperitoneum behind stomach: head nestled into “c-shaped” curvature of duodenum with body extending to left about 15.2 cm (6 in) and ending as a tapering tail in hilum of spleen [curious mix of exocrine (secreting digestive enzymes) and endocrine (releasing hormones into blood) functions]
Pancreas
• exocrine part = arises as little grape-like cell clusters, each called an acinus
(plural = acini), located at terminal ends of pancreatic ducts, secreting enzyme-rich pancreatic juice into tiny merging ducts that form 2 dominant ducts [larger duct, Wirsung, fuses with common bile duct (carrying bile from liver and gallbladder) just before entering the duodenum via a common opening (hepatopancreatic ampulla)]; smooth muscle sphincter of hepatopancreatic ampulla controls release of pancreatic juice and bile into small intestine; second and smaller pancreatic duct, the accessory duct (duct of Santorini), runs from pancreas directly into duodenum, approximately 1 inch above hepatopancreatic ampulla.
• Scattered through sea of exocrine acini are small islands of
endocrine
cells, islets of Langerhans, producing hormones pancreatic polypeptide, insulin, glucagon, and somatostatin
PANCREAS ANATOMY
stomach
esophagus
ductus choledocus
duodenum
duct of
Santorini duct of
Wirsung
pancreas
Pancreas
1. PROTEASES (70%)
Endopeptidases (trypsin, chymotrypsin, elastases)
Exopeptidases (carboxypeptidases)
trypsinogen trypsin activates all other precursors
enterokinase (duct walls)
2. NUCLEASES (DNAase, RNAase)
3. PANCREATIC AMYLASE (hydrolyse starch and gl;ycogen)
4. PANCREATIC LIPASE (triglycerides fatty acids and glycerol)
PANCREATIC SECRETIONS
REGULATION OF SECRETION
1. SECRETIN
food in stomach
release of stomach acid into duodenum
release of secretin into blood by duodenal cells
secretion of bicarbonate by duct cells
alkaline pH (ideal for pancreatic enzymes)
2. PANCREOZYMIN (cholecystokinen)
amino acids and fats in intestine
release of pancreozymin by intestinal mucosa
into blood
relase of pancreatic enzymes into the intestine
3. GASTRIN
food in stomach gastrin secretion
by stomach mucosa
release of pancreatic enzymes into the intestine
4. AUTONOMIC INNERVATION (vagus nerve)
Pancreas: Histology
pancreatic acini
islet of
Langerhans
islet of
Langerhans
BV
pancreatic lobe
Pancreas: Histology
LARGE SECRETORY DUCT
INTERLOBULAR DUCT
acinus
simple cuboidal
epithelium
simple columnar
epithelium
PANCREATIC SECRETORY DUCTS
Pancreas: Histology
interlobular duct
intercalated
duct
nerve
acinus pyramidal secretory cell basal basophilia
(rough ER)
zymogen granules
centro- acinar cells blood
vessel
rough endoplasmic reticulum
golgi apparatus
golgi vesicles
condensing vacuoles
zymogen granules
merocrine secretion (exocytosis)
Exocrine Pancreas: Histology
intercalary duct
intercalary duct
centroacinar cell
INTERCALARY DUCTS AND CENTROACINAR CELLS
Pancreas: Histology
PANCREATIC EXOCRINE SECRETORY CELL
zymogen
granules
centroacinar cell
CELL BIOLOGY OF PANCREATIC SECRETION
1. SYNTHESIS
14 C -leucine + tRNA
14 C-amino-acyl tRNA
mRNA for chymotrysinogen
ribosomes
chymotrysinogen
2. SEGREGATION
mRNA
ribosomes
polypeptide
RER cisterna
3. INTRACELLULAR TRANSPORT
RER
transitional elements
golgi
apparatus
golgi vesicles
4. CONCENTRATION
H2O
H2O
condensing vacuoles
5. INTRACELLULAR
STORAGE
zymogen
granules
6. DISCHARGE
exocytosis
ISLET OF LANGERHANS
alpha cell
beta
cell
blood
capillary
acinus
beta cell
alpha
cell fenestrated
capillary
(insulin)
(glucagon) vascular pole
(secretion by exocytosis)
INSULIN- increases membrane permeability to glucose
promotes glycogenesis decrease blood glucose levels
GLUCAGON - promotes glycogenolysis increases blood glucose levels
“ ANTAGONISTIC HORMONES”
Pancreas: Histology
Pancreas: Histology
ISLET OF LANGERHANS
Pancreas: Histology
ISLET OF LANGERHANS - TEM
STAINED ALPHA AND BETA CELLS
ALPHA CELLS BETA CELLS
intercalary duct
intercalary duct
centroacinar cell
INTERCALARY DUCTS AND CENTROACINAR CELLS
Pancreas: Histology
Pancreas: Histology
Gallbladder
= 8–10 cm (~3–4 in) long, nested in a shallow area on posterior aspect of right liver lobe , muscular sac storing, concentrating, and, when stimulated, propelling bile into duodenum via common bile duct, divided into 3 regions:
1.fundus = widest portion, tapering medially into 2.body, which in turn narrows to become 3.neck, angling slightly superiorly as it approaches hepatic duct; cystic duct = 1–2 cm
(less than 1 in) long, turning inferiorly as it bridges neck and hepatic duct.
Gallbladder simple columnar epithelium organized in rugae, similar to those of
stomach, absorbing water and ions from bile and concentrating it by up to 10-fold: no submucosa in gallbladder wall and wall’s middle, muscular coat is made of smooth muscle fibers [when contracting, gallbladder’s contents ejected through cystic duct and into bile duct]
visceral peritoneum reflected from liver capsule holds gallbladder against liver and forms outer coat of the gallbladder.
Gallbladder: Histology
Gallbladder: Histology
Liver, Pancreas, and Gallbladder
Anatomy-Histology Correlate
-The liver and gallbladder play important roles in
digestion via the production and storage of bile. The
liver is also the major organ for metabolism and
detoxification. The pancreas also produces digestive
enzymes to break down proteins, sugars, and fats.
- The processes described above are the exocrine
functions of the liver and gallbladder. But they also have
endocrine roles, secreting compounds into the
bloodstream. The hepatocytes produce albumin,
fibrinogen, and thrombin, for example. The pancreatic
islets produce insulin, glucagon, and somatostatin.
- The liver, gallbladder, and pancreas receive blood
supply from the celiac trunk. One main branch is the
common hepatic artery, leading to the hepatic artery
proper that branches into left and right hepatic
arteries to supply the liver. The right hepatic artery
gives off the cystic artery to supply the gallbladder.
- The pancreas is supplied by multiple vessels. The
body and tail are supplied by the dorsal, inferior, and
great pancreatic arteries, which all branch off the
splenic artery (another main branch of the celiac
trunk). The head, neck, and uncinate process are
supplied by anastomoses of arteries branching off the
celiac trunk and superior mesenteric artery. The
gastroduodenal artery, from the common hepatic
artery, divides into the anterior and posterior superior
pancreaticoduodenal arteries. They anastomose with
inferior branches of the inferior pancreatico-
duodenal artery from the superior mesenteric artery.
The same arteries supply the duodenum.
-The liver has diaphragmatic and visceral surfaces which contact the diaphragm and abdominal viscera,
respectively. Note the right triangular, left triangular, and coronary ligaments that attach to the diaphragm.
Note also the bare area not covered by peritoneum. Anteriorly, there is a fold of peritoneum connecting the liver to
the umbilicus called the falciform ligament, which contains the round ligament or ligamentum teres. It is the
remnant of the umbilical vein that brought oxygenated blood from the placenta to the fetus heart. The ligamentum
venosum is the remnant of the fetal ductus venosus that shunted blood from the umbilical vein to the inferior vena
cava to bypass the liver. In the adult liver, the porta hepatis includes the hepatic arteries from the hepatic artery
proper, the hepatic portal vein, and the hepatic and cystic ducts joining to form the common bile duct.
- The portal vein brings nutrients and other compounds absorbed by the GI tract to be stored and/or processed.
- Anatomical lobes: Note how the inferior vena cava, gallbladder, ligamentum teres, ligamentum venosum, and
porta hepatis form an “H” shape on the visceral surface. It divides the liver into 4 anatomical lobes based on outer
appearance – the right, left, caudate, and quadrate lobes.
- Functional lobes: These are based on the distribution of the hepatic arteries, portal vein, and hepatic bile duct.
The inferior vena cava and the gallbladder serve as the dividing line between the functional right and left lobes.
- The liver is divided into many hepatic lobules. Inflow to the liver
involves hepatic arteries, which bring oxygenated blood to hepatic
tissue, and portal veins, which bring nutrients and other compounds
absorbed by the GI tract to be processed and/or stored in the liver.
Outflow also involves two routes – hepatic veins which drain into
the inferior vena cava and the common hepatic duct which joins the
cystic duct and empties bile into the duodenum.
- Major characteristics of the liver are portal triads (labeled “portal”
in bottom left and shown in the middle) and central veins (labeled
in bottom left and shown in the right). Red arrows indicate direction
of blood flow within blood sinusoids flanking cords of liver cells.
- Note the portal triad contains 1) the portal vein, 2) the hepatic
artery, and 3) the bile duct. Each has its typical appearance. The
central vein is lined with endothelial cells, with perforations into
which the sinusoids empty.
- The central veins lead to sublobular veins, which reach collecting veins,
hepatic veins, and finally the inferior vena cava. The venous outflow of
the liver has no regard to the organization of the lobules.
- The liver sinusoids are shown in higher magnification in the bottom left.
They are dilated, capillary-like vessels lined by fenestrated, discontinuous
epithelium (labeled “e”). Interspersed among the endothelial cells are
Kupffer cells (labeled “k”), which are fixed macrophages within the
hepatic tissue. They have distinct cytoplasm that may enter the sinusoidal
lumen and function like other macrophages within the body. They also
break down damaged red blood cell hemoglobin.
- In the bottom middle panel, there are many spaces between the
hepatocytes and sinusoidal epithelial cells marked by arrowheads. They
are referred to the space of Disse where exchange between hepatocytes
and blood flow takes place.
- Once again, in the bottom right, we review the Kupffer cell, endothelial
cell of the liver sinusoid, and the space of Disse.
- As mentioned earlier, the liver
has both endocrine and
exocrine functions. The various
proteins that hepatocytes
secrete enter the bloodstream
via the liver sinusoids. The liver
also secretes bile in the
conventional exocrine fashion.
- The hepatocytes secrete bile
into sealed extracellular spaces
called bile canaliculi. The
typical “chicken-wire”
appearance is more easily
visualized with silver stain.
- The liver lobules can be defined in 3 ways:
- 1) Classic lobule – centered around the central vein with the portal triads at
each corner. Shown below on the left, the classic lobule may not always be
hexagonal in shape.
- 2) Portal lobule (not shown) – centered on the portal triad, based on bile
secretion, and approximately triangular in shape.
- 3) Liver acinus of Rappaport – this is the most functionally important
classification. Shown below on the right, the acinus is roughly oval in shape
with 2 central veins and 2 portal triads on opposite ends. Based on the blood
flow within hepatic tissue, the acinus is divided into 3 zones. Cells in different
zones are specialized for different activity. Zone 1 cells, being closest to the
portal triads and hence most oxygenated blood, have the most drug-
metabolizing enzymatic activity. Following that same reasoning, zone 3
hepatocytes near the central veins are most susceptible to ischemia.
- Once again, inflow to the liver involves
oxygenated blood via hepatic arteries and
absorbed nutrients and compounds from
the GI tract via the hepatic portal veins.
- All venous drainage from the GI tract and
abdominal visceral organs enters the portal
system back to the liver. The overall order
is as following: arteries → capillaries →
veins → portal vein → hepatic sinusoids →
veins → vena cava → heart.
- In contrast, the caval system is as
following: arteries → capillaries → veins →
vena cava → heart. Obviously, this is the
circulatory system within the rest of the
body.
- The portal and caval system are not
exclusive from each other. There are 4 sites
of portocaval anastomoses:
- 1) esophageal veins
- 2) paraumbilical veins
- 3) rectal veins
- 4) retroperitoneal veins
- If there is liver damage or cirrhosis –
accumulation of fibrous tissue that
constricts the sinusoids – there may be
portal hypertension. This may lead to
varicose veins at the 4 sites of
anastomoses.
- The gallbladder is found under the right lobe of the liver. Its
function is to store bile produced by the liver, which leaves via the
cystic duct. It also enters the gallbladder in the cystic duct,
traveling retrograde when the bile is not needed for digestion. Note
the fundus, body, neck, and infundibulum of the gallbladder.
- Note the right and left hepatic ducts coming together as the
common hepatic duct, joining the cystic duct to form the
common bile duct. This descends to the 2nd part of the
duodenum, is joined by the pancreatic duct, and empties its
contents into the duodenal lumen via the major duodenal papilla.
- The gallbladder is supplied by the cystic artery, which is
extremely important to find during a cholecystectomy. In most
people it branches off the right hepatic artery, but could also come
off the left hepatic, proper hepatic, or gastroduodenal arteries.
- Note the extensive folds of mucosa extending into the lumen,
consisting of tall, simple columnar epithelium. The underlying
connective tissue is comprised of lamina propria, with no distinctly
defined submucosa. There are scattered bundles of smooth muscle
in the muscularis. The adventitia has rather dense connective
tissue connecting the gallbladder to the liver.
- Finally, we will look at the pancreas. To
review: The head of the pancreas and
duodenum are supplied from both the celiac
trunk and the superior mesenteric artery.
- The body and tail of the pancreas are
mostly supplied by branches of the splenic
artery, namely the dorsal, greater, and
inferior pancreatic arteries.
- Piece of advice: It can be very confusing
when identifying these arteries. First orient
yourself, note whether the duodenum is in
anatomical position or reflected (as it is on
the bottom left), and identify where the
arteries branch from and where they lead.
- The pancreas contains multiple ducts, but the main pancreatic
duct runs from the tail to the head of the pancreas. There may be a
smaller accessory pancreatic duct. They join the common bile
duct to empty into the duodenum. The pancreas is retroperitoneal.
- Histologically, we can see the septa (S) between pancreatic
lobules with interlobular ducts (D). As mentioned above, the
pancreas also has both exocrine and endocrine functions. Most of
the bottom left panel is filled with exocrine pancreatic tissue.
Secretory portions are called acini. The scattered endocrine islets
of Langerhans (I) are paler staining.
- An islet is magnified in the bottom right. It is a compact mass of
epithelial cells that receive rich vascular supply (arrows). It is
typically very difficult to identify the different cell types in the islets.
Briefly, the alpha cells secrete glucagon, the beta cells secrete
insulin, and the delta cells secrete somatostatin.
-Once again, most of the pancreas contains exocrine acini. Pancreatic enzymes are very diverse, including
extremely efficient proteases, lipases, and amylases.
- Separate acini are shown in the left. The pancreatic acinar or secretory cells are polarized, meaning the basal
portions are filled with basophilic rough ER. The apical regions are filled with zymogen granules that contain
many stored pro-enzymes.
- Centroacinar cells, with paler staining, can be seen in the middle of some acini and mark the beginning of the
duct system (marked “A” in the middle panel). They converge at “B” to form intercalated ducts, marked as “C”.
The intercalated duct cells may be hard to identify, but they actively pump water and bicarbonate into the duct
lumen. Intercalated ducts empty into interlobular ducts, marked as “small duct” in the bottom right, which lead to
the main pancreatic duct.