Re: Carole, ..repeat of pancreas 101(basics)

[Guest guest]

< This is technical in parts, but is very informative about " normal "

pancreatic structure & function.

jang

> I didn't get that post for whatever reason. If you still have it

in your files, could you please forward it to me...sounds very

interesting. Thanks and hope you are having a good day!

Hugs & Prayers

Carole

ditto that, as I didn't get it either!

Thanks

Here ya go guys..........

Subject: pancreas 101(basics)

Gross and Microscopic Anatomy of the Pancreas

The pancreas is an elongated organ, light tan or pinkish in color,

that lies in close proximity to the duodenum. It is covered with a

very thin connective tissue capsule which extends inward as septa,

partitioning the gland into lobules. The bulk of the pancreas

is composed of pancreatic exocrine cells and their associated ducts.

Embedded within this exocrine tissue are roughly one million small

clusters of cells called the Islets of Langerhans, which are the

endocrine cells of the pancreas and secrete insulin, glucagon

and several other hormones.

Pancreatic exocrine cells are arranged in grape-like clusters called

acini. The exocrine cells themselves are packed with membrane-bound

secretory granules which contain digestive enzymes that are exocytosed

into the lumen of the acinus. From there these secretions flow into

larger and larger, intralobular ducts, which eventually coalesce into

the main pancreatic duct which drains directly into the duodenum.

The lumen of an acinus communicates directly with intralobular ducts,

which coalesce into interlobular ducts and then into the major

pancreatic duct. Epithelial cells of the intralobular ducts actually

project " back " into the lumen of the acinus, where they are called

centroacinar cells. The anatomy of the main pancreatic duct varies

among species. In some animals, two ducts enter the duodenum rather

than a single duct. In some species, the main pancreatic duct fuses

with the common bile duct just before its entry into the duodenum.

Control of Pancreatic Exocrine Secretion

As you might expect, secretion from the exocrine pancreas is

regulated by both neural and endocrine controls. During interdigestive

periods, very little secretion takes place, but as food enters the

stomach and, a little later, chyme flows into the small intestine,

pancreatic secretion is strongly stimulated. Like the stomach, the

pancreas is innervated by the vagus nerve, which applies a low level

stimulus to secretion in response to anticipation of a meal. However,

the most important stimuli for pancreatic secretion comes from three

hormones secreted by the enteric endocrine system:

Cholecystokinin: This hormone is synthesized and secreted by enteric

endocrine cells located in the duodenum. Its secretion is strongly

stimulated by the presence of partially digested proteins and fats in

the small intestine. As chyme floods into the small intestine,

cholecystokinin is released into blood and binds to receptors on

pancreatic acinar cells, ordering them to secrete large quantities of

digestive enzymes.

Secretin: This hormone is also a product of endocrinocytes located in

the epithelium of the proximal small intestine. Secretin is secreted

in response to acid in the duodenum, which of course occurs when

acid-laden chyme from the stomach flows through the pylorus. The

predominant effect of secretin on the pancreas is to stimulate duct

cells to secrete water and bicarbonate. As soon as this occurs, the

enzymes secreted by the acinar cells are flushed out of the pancreas,

through the pancreatic duct into the duodenum.

Gastrin: This hormone, which is very similar to cholecystokinin, is

secreted in large amounts by the stomach in response to gastric

distention and irritation. In addition to stimulating acid

secretion by the parietal cell, gastrin stimulates pancreatic acinar

cells to secrete digestive enzymes.

Stop and think about this for a minute - control of pancreatic

secretion makes perfect sense. Pancreatic secretions contain enzymes

which are needed to digest proteins, starch and triglyceride. When

these substances enter stomach, and especially the small intestine,

they stimulate release of gastrin and cholecystokinin, which in turn

stimulate secretion of the enzymes of destruction.

Pancreatic secretions are also the major mechanism for neutralizing

gastric acid in the small intestine. When acid enters the small gut,

it stimulates secretin to be released, and the effect of this hormone

is to stimulate secretion of lots of bicarbonate. As proteins and fats

are digested and absorbed, and acid is neutralized, the stimuli for

cholecystokinin and secretin secretion disappear and pancreatic

secretion falls off.

Exocrine Secretions of the Pancreas

Pancreatic juice is composed of two secretory products critical to

proper digestion: digestive enzymes and bicarbonate. The enzymes are

synthesized and secreted from the exocrine ascinar cells, whereas

bicarbonate is secreted from the epithelial cells lining small

pancreatic ducts.

Digestive Enzymes

The pancreas secretes a magnificent battery of enzymes that

collectively have the capacity to reduce virtually all digestible

macromolecules into forms that are capable of, or nearly capable

of being absorbed. Three major groups of enzymes are critical to

efficient digestion:

Proteases

Digestion of proteins is initiated by pepsin in the stomach, but the

bulk of protein digestion is due to the pancreatic proteases. Several

proteases are synthesized in the pancreas and secreted into the lumen

of the small intestine. The two major pancreatic proteases are

trypsin and chymotrypsin, which are synthesized and packaged into

secretory vesicles as an the inactive proenzymes trypsinogen and

chymotrypsinogen. As you might anticipate, proteases are rather

dangerous enzymes to have in cells, and packaging of an inactive

precursor is a way for the cells to safely handle these enzymes. The

secretory vesicles also contain a trypsin inhibitor which serves as an

additional safeguard should some of the trypsinogen be activated to

trypsin; following exocytosis this inhibitor is diluted out and

becomes ineffective - the pin is out of the grenade.

Once trypsinogen and chymotrypsinogen are released into the lumen

of the small intestine, they must be converted into their active forms

in order to digest proteins. Trypsinogen is activated by the enzyme

enterokinase, which is embedded in the intestinal mucosa.

Once trypsin is formed it activates chymotrypsinogen, as well as

additional molecules of trypsinogen. The net result is a rather

explosive appearance of active protease once the pancreatic

secretions reach the small intestine.

Trypsin and chymotrypsin digest proteins into peptides and peptides

into smaller peptides, but they cannot digest proteins and peptides to

single amino acids. Some of the other proteases from the pancreas, for

instance carboxypeptidase, have that ability, but the final digestion

of peptides into amino acids is largely the effect of peptidases in

small intestinal epithelial cells. More on this later.

Pancreatic Lipase

The major form of dietary fat is triglyceride, or neutral lipid. A

triglyceride molecule cannot be directly absorbed across the

intestinal mucosa. Rather, it must first be digested into a

2-monoglyceride and two free fatty acids. The enzyme that performs

this hydrolysis is pancreatic lipase, which is delivered into the

lumen of the gut as a constituent of pancreatic juice. Sufficient

quantities of bile salts must also be present in the lumen of the

intestine in order for lipase to efficiently digest dietary

triglyceride and for the resulting fatty acids and monoglyceride to

be absorbed. This means that normal digestion and absorption of

dietary fat is critically dependent on secretions from both the

pancreas and liver.

Pancreatic lipase has recently been in the limelight as a target for

management of obesity. The drug orlistat (Xenical) is a pancreatic

lipase inhibitor that interferes with digestion of triglyceride

and thereby reduces absorption of dietary fat. Clinical trials support

the contention that inhibiting lipase can lead to significant

reductions in body weight in some patients.

Amylase

The major dietary carbohydrate for many species is starch, a storage

form of glucose in plants. Amylase is the enzyme that hydrolyses

starch to maltose (a glucose-glucose disaccharide), as well as the

trisaccharide maltotriose and small branchpoints fragments called

limit dextrins. The major source of amylase in all species is

pancreatic secretions, although amylase is also present in saliva of

some animals, including man.

Other Pancreatic Enzymes

In addition to the proteases, lipase and amylase, the pancreas

produces a host of other digestive enzymes, including ribonuclease,

dioxynuclease, gelatinase and elastase.

Bicarbonate and Water

Epithelial cells in pancreatic ducts are the source of the bicarbonate

and water secreted by the pancreas. The mechanism underlying

bicarbonate secretion is essentially the same as for acid secretion

parietal cells and is dependent on the enzyme carbonic anhydrase. In

pancreatic duct cells, the bicarbonate is secreted into the lumen

of the duct and hence into pancreatic juice.

Source: Republished with permission by Bowen -

Hypertexts for Biomedical Sciences

[Guest guest]

> In a message dated 1/21/01 11:57:59 AM Eastern Standard Time,

> jang2@m... writes:

>

>

> > Here ya go guys..........

> >

>

> Thanks Jang....hope you are having a good day! Somehow I knew you

would come

> through for us. But then, you always do!

>

> Hugs & Prayers

> Carole

ditto, ditto, ditto. Thanks jang! You are the best!

christine