Pancreas

Bulk of the tissue is exocrine pancreas; within this are the endocrine cells (pancreatic beta cells) responsible for
glucose homeostasis. (Make sure know difference between endocrine and exocrine)
Pancreas secretes enzymes and HCO3- and H2O, particularly by ductal cells
It is an elongated organ found in rear of abdomen behind/underneath the
liver
It has a ductal system. Bile duct and pancreatic duct merge just before
contents of pancreas and bile empty into the duodenum. Content of
stomach is showered with pancreatic and bile secretions
Microscopic detail of pancreas: grape similar to acinar cells of salivary glands

Pancreatic secretion:
Acinar cells are vital in production of enzymes for digestion but produce small amounts of fluid to allow enzyme to
flow down the ducts.
Ductal cells are highly secretory and secrete water and bicarbonate and flush enzymes down. Water dilutes acid and
buffer combines with acid to produce CO 2 + H2O
Functions of Pancreatic Secretion
1) Digestion of proteins
Protolytic enzymes of pancreas are also inactivated
similarly seen in pepsinogen. These are activated once reaching lumen of Small intestine.
Enterokinase is found in brush border of E.Cells of Small Intestine
2) Digestion of carbs: mainly pancreatic amylase.
Salivary amylase also does the job and is only found in mouth and oesophagus but deactivates once inside the
stomach due to acid
3) Digestion of fat: Pancreatic lipase and bile salts are responsible for fat digestion
4) Neutralisation of acid by HCO3-
Bicarbonate pancreatic juice protects mucosa of epithelial lining of small intestine - it prevents too much acidity from
attacking membrane and maintains pH for enzyme activity.
All enzymes have optimum pH and most are neutral- pH7. Pepsin works in acidic pH.

Control of Secretion
Largely by hormones: Secretin and CCK
Secretin – 27Aa long peptide – formed by special S cells in Small
intestine wall
As stomach content comes into duodenum, acidity stimulates
endocrine cells to produce secretin which travels via blood and into
the pancreas and stimulates duct cells to produce bicarbonate
It is specific and acts only on pancreatic duct cells
Production and secretion of HCO3- ions neutralises acidity and
hence is –ve feedback
CCK – various types but can operate short/long chain: 8/33Aa but in gut tends to be around 33Aa
CCK produced by I cells found in upper part of S.I in mucosa.
Products of fat and protein digestion (peptides and fatty acids) in the duodenum stimulate release of CCK from these
endocrine cells which travel via blood and stimulate acinar cells of pancreas and affects enzyme secretion.
Enzyme secreted into duodenum and act on fat and protein
Hence positive feedback – more enzyme secreted, more stimulants produced – more enzymes released and hence
maximal enzyme secretion whilst in duodenum
When fat and protein run out, and food moves away from upper part of S.I then CCK secretion reduces
Nerves also control pancreatic secretion – overlap with hormone control. But their main neural control is via
parasympathetic nerves which stimulate enzyme secretion by the acinar cells
Enzyme secretion
Small amount of fluid secretion also occurs to allow flushing environment for enzymes
of acinar cells
Acini are E.cells joined by junctional complexes.
On basolateral membrane are cell surface receptors for ACh and CCK which travel via
blood
Both receptors have same end result once activated – increase intracellular Ca 2+.
Within acinar cells are specialised vesicles containing enzymes and when Ca 2+ conc.
goes up, this causes exocytosis, vesicles fuse with apical membrane and enzymes are released into the lumen.

Prevention of auto digestion

Inert precursors/enzymes are secreted to prevent breakdown of proteins within membrane of pancreas
Enzyme packaging in dehydrated format also prevent activation.
Zymogen ensure they move in the correct direction
Trypsin inhibitor produced from pancreas alongside enzymes is a key activator of these enzymes. These enzymes
only activated when they reach the small intestine

Pancreatitis: inflammation caused by auto digestion  incomplete digestion of fats & protein = malabsorption
Acute Pancreatitis: gall stones block common bile duct; juices cannot reach duodenum. Enzymes in pancreas are
activated and breakdown protein in membrane. These can enter the blood and spread into the body further
destroying proteins elsewhere.
Common test is to measure enzyme conc in the blood
Fats and proteins stop being absorbed in gut and so malabsorption so causes fatty diarrhoea – steatorrhoea

Ductal secretion
Bicarbonate + water stimulated by secretin
It activates enzymes which increase 2nd messenger –cAMP.
Production of bicarbonate: H2O + CO2 and enzyme to form HCO3-
ions and protons
Protons move outside via basolateral membrane
Sodium bicarbonate co-transports bringing bicarbonate from
interstitial fluid into the cell using Na gradient drive
Apical membrane: Cl- channel allows Cl- ions to escape from cell
and then exchanges with bicarbonate cells via exchanger so
overall result is exit of bicarbonate via apical membrane.
This is important as this Cl- channel is activated by cAMP. Also note this channel is defective in cystic fibrosis. So
when not present /malfunctioned, pancreatic secretion is affected, less bicarbonate secreted, enzyme delivery is also
affected.

Bile secretion
Liver is important as it secretes the bile constantly. Bile not only involved in digestion.
Bile is secreted in between meals and directed to gall bladder and stored here 8/9/10 hours.
Bile duct and pancreatic duct merge with common bile duct.
Sphincters control opening of ducts. Before duodenum is major sphincter of oddi – thickening of smooth muscle
which is usually constricted

Bile composition:
 Bile salts/acids, cholesterol, lecithin – emulsifying effects of bile. Primarily
bile salts do this
 Responsible for fat digestion and production of micelles which transport
products to S.I
 Bilirubin (recycled haemoglobin) gives bile the brown colouration and hence
in faeces, heavy metals (toxic), steroids (hormones which liver breaks down
but cannot be processed by kidneys) all involved in excretion
 HCO3- ductal system within liver secretes bicarbonate could be a by-product of liver metabolism or have a
functional role as food enters duodenum
Substances absorbed by S.I. go into liver via portal
vein via hepatocytes
O2 blood mixes with blood containing nutrients and
is dealt with hepatocytes which have sinusoids
between them
Hepatocytes have a secretory function
Within sinusoids are also bile ducts – substances are
taken into the hepatocytes from the blood and they
are excreted into bile ductal system
Liver cells are polarised cells and appear to have tight junctional structures at both ends
Basolateral side is usually the side lining the blood
Molecules are metabolised and secreted into blood or secreted into bile canaliculi

2 stage secretion:
1) Canalicular secretion: include bile salts, organic anions and cholesterol transported into bile canaliculi
2) Ductal secretion: produces bicarbonate and H2O similarly to pancreas
Constant production of bile is stored in gall bladder between meals – it concentrates it to reduce the volume by
absorbing ions and causes water reabsorption which further reduced fluid volume.

Enterohepatic circulation
Bile salts are recycled in order to complete fat digestion: they
are secreted into duodenum to digest fat, but when fat moves
down into ileum, bile acids are actively reabsorbed into blood
and go into portal blood and return to liver
By the time chyme reaches the ileum, fat is all digested and so
bile acids can be reabsorbed
15g of salts needed to digest normal meal but body only has 3g and so to allow complete digestion, they are recycled
5x.

Control
Choleretics – stimulate bile secretion by the liver
 secretin which is stimulated by presence of protons in duodenum
  By vagus nerve which is active in gastric digestion
 Bile salts: during absorption, bile salts are reabsorbed into hepatocytes and stimulate them to release more
bile salts
Cholagogues: at the start of food digestion. They stimulate bile release from gall bladder
CCK stimulated by peptides and Fatty acids (products of digestion) It is released into blood – complication:
CCK causes contraction of gall bladder but can also relax smooth muscle in sphincter of oddi – and so bile is delivered
into duodenum
More recently, CCK also acts as a paracrine transmitter like 5-HT.
So it stimulates enteric nerves within the gut via the vagus nerve.
Vagal fibres go to gall bladder which release local ACh causing gall
bladder contraction
Other vagal fibres go to sphincter of oddi – these fibres cause
relaxation of this sphincter
These vagal fibres innervate enteric nerves which release NO 2
and VIP
ACh and CCK cause smooth muscle contraction. NO 2
(neurotransmitter) and VIP is released but allows relaxation of
sphincter of oddi

Biliary disease:
Causes – damage to hepatocytes – hepatitis
Blockage of bile ducts
Less bile is delivered so less malabsorption of fats occurs. Fat moves through small intestine into colon and is
osmotically active which pulls in water and causes fatty diarrhoea: steatorrhoea
Not dangerous and is seen in fat loss treatments: but causes steatorrhoea and loss of fat soluble vitamins.

Jaundice: problem with liver/biliary system

Bilirubin – when it can’t be excreted into intestine, it accumulates in bodily tissues giving yellow colouration