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Ingegneria delle tecnologie per la salute Fondamenti di anatomia e istologia aa. 2019-20 Lesson 7. Digestive system and peritoneum
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Page 1: Fondamenti di anatomia e istologia › dati › corsi › 95005 › 95940-Lez7c Apparato... · 2020-05-08 · Liver: Histology 1 hepatocytes ... stomach acid into duodenum release

Ingegneria delle tecnologie per la salute

Fondamenti di anatomia e istologia

aa. 2019-20

Lesson 7. Digestive system and peritoneum

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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)

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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:

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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:

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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:

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Liver: Histology

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Liver: Histology

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Liver: Histology

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Liver: Histology

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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.

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Liver: Histology portal triad

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Liver: Histology portal triad

Blood flow

Bile flow

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Liver: Histology

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Liver: Histology

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Liver: Histology

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Liver: Histology

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Liver: Histology

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Liver: Histology

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Liver: Histology

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Liver: Histology

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Liver: Histology

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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]

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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)]

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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.

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Liver & Pancreas

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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]

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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

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PANCREAS ANATOMY

stomach

esophagus

ductus choledocus

duodenum

duct of

Santorini duct of

Wirsung

pancreas

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Pancreas

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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

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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)

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Pancreas: Histology

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pancreatic acini

islet of

Langerhans

islet of

Langerhans

BV

pancreatic lobe

Pancreas: Histology

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LARGE SECRETORY DUCT

INTERLOBULAR DUCT

acinus

simple cuboidal

epithelium

simple columnar

epithelium

PANCREATIC SECRETORY DUCTS

Pancreas: Histology

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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

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intercalary duct

intercalary duct

centroacinar cell

INTERCALARY DUCTS AND CENTROACINAR CELLS

Pancreas: Histology

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PANCREATIC EXOCRINE SECRETORY CELL

zymogen

granules

centroacinar cell

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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

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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”

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Pancreas: Histology

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Pancreas: Histology

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ISLET OF LANGERHANS

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Pancreas: Histology

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ISLET OF LANGERHANS - TEM

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STAINED ALPHA AND BETA CELLS

ALPHA CELLS BETA CELLS

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intercalary duct

intercalary duct

centroacinar cell

INTERCALARY DUCTS AND CENTROACINAR CELLS

Pancreas: Histology

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Pancreas: Histology

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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.

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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.

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Gallbladder: Histology

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Gallbladder: Histology

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Liver, Pancreas, and Gallbladder

Anatomy-Histology Correlate

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-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.

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-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.

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- 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.

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- 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.

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- 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.

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- 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.

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- 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.

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- 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.

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- 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.

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-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.


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