Structure

Pancreas: compound alveolar gland ( like salivary gland), cells exocytose zymogen granules which contain
enzymes to pancreatic duct lumen (single duct drains into pancreatic duct of Wirsung, joins bile duct= ampulla
of Vater)

GI secretions
Hypotonic (compared to plasma; because of NaCl loss, salivary acini extract NaCl, replace with K, HCO3),
alkaline (to neutralize gastric secretions)
Saliva: amylase (break down starch); lysosome, IgA; Lubrication (mucin)
Stomach: parietal/oxyntic cells (HCL; sterilizes, hydrolysis, IF; Vit B12 absorption), chief/zymogen/peptic
cells (pepsingogen; protein digestion; lipase), mucus cells (mucus, HCO3, peptides to stabilize the mucus-
HC03 layer; protects stomach). Most are secreted in fundus, body.
Pancreas: juice/bile/intestinal is alkaline/ Ph 6-7 (due to a lot HCO3). Trypsinogen cleaved to trypsin which
activates pancreatic enzymes, including lyso-PC which damages cells. Pancreatitis is where the phospholipase
A2 is prematurely activated.
Bile:
o Alkaline. Contains bile acids (mainly, reduce surface tension, emulsify fat);bile pigments. 95% are
reabsorbed in the intestine, and liver re-excreted (enterohepatic circulation).. Bile acids (cholic acid,
 chendeoxycholic acid) are made from cholesterol, conjugated with glycerine, taurine. Bacteria in colon
convert cholic acid to deoxycholic acid; chenodeoxycholic acid to lithocholic acid. Some
chenodeoxycholic are converted to ursodeoxycholic (2nd bile acids, as made from bacteria). Post-
deconjugation, absorbed by diffusion. Can be absorbed as conjugated in the terminal ilem (mostly),
colon. If not abdosirbed then secreted in stools.
Intestines:
o H20 moves passively through the intestines due to the electrochemical gradient (active transport of
ions/solutes like glucose uptake 2nd to Na, fluid 2nd to Cl). H20 moves until osmotic pressure of
intestine is = to plasma (which occurs in jejunum)
Neural control:
o Enteric nervous system: submuscosa (Meissner plexus) (generally glandular epithelium, intestinal
endocrine cells/secretion, submucosal BV), between oterh longitudinal, middle circular: myenteric
plexus/ Auerbach plexus (generally motor function). Neurotransmitters: ACHs, serotonin, epinephrine,
GABA, ATP. PNS: pre-ganglionic mainly vagal, sacral n; involve ACh. SNS are post-ganglionic, but
many end on post-ganglionic ACh n where they secret norepinephrine (which inhibits AChs secretion.
o Before eating: neural mechanism where salivary and stomach secretions are already initiated

o
Stomach (neural, hormonal):
PNS: vagi, Celiac plexus (SNS)
Dorsal vagal complex in brain, actives as gastric secretion. It leads to enteric nerve
hormone section, then activates G-cells and enterchromaffin-like cells. G-cells (gastrin;
stimulated by gastrin-releasing peptide/GRP or bombesin which is a neurotransmitter
released from enteric nerve endings; and oligopeptides in the gastric lumen) bind to
chief , parietal cells, enterchromaffin-like cells ( release histamine which binds to H2-
receptors, activate parietal cells); Enteric nerve endings release ACh which stimulate
chief, parietal cells.
As food digests then gastrin, histamine, ACh stretch receptors, secretion responses
amplified (synergistic effect)
Pancreas (hormonal):
Secretin stimulates pancreas (a lot of fluid, high in HC03, min enzymes, alkaline); bile
secretion.
CCK releases zygomen granules, pancreatic secretion (min fluid; lots of enzymes);
mediated by phospholipase C.
ACh acts on acinar cells by phospholipase C, stimulates zygomen granules
Vagi stimulation stimulates pancreas secretion (lots of enzymes)
Summary of hormones:
Gastrin (circulation time 15 mins): G cells in the antrum produce gastrin. Kidney, small intestine inactivate
gastrin. Gastrin secretion affected by stomach contents (amino acids), rate of Vagus discharge (post-ganglionic
fibres secrete GRP ), blood born factors. Gastrin stimulates gastric acid, pepsin secretion; stomach/small/large
intestine mucosal hypertrophy; via the CCK=B receptor (brain).
CCK (circulation time 5 mins): I cells in the upper small intestine, distal ileum, colon secrete CCK which
stimulates pyloric sphincter contraction; pancreas secretion, gall-bladder contraction, relaxation to sphincter of
Oddi, augmets secretin (stiulates alkaline pancreatic juicec), inhibits gastric emptying. Binds to CCK-A
(periphery mainly; brain). Food (amino acids) contact with intestines; intestinal/ pancreas releasing proteins
(CCK-releasing peptide) stimulate CCK secretion. Less CCK-releasing peptide as go further down colon as
they are no longer digesting dietary proteins.
Secretin (circulation time 5 mins): S cells in the upper intestine produce S cells which stimulates pancreatic
juice (alkaline, HCO3, H20, neutralizes acid) via the CAMP; pancreatic enzyme secretion, gastric acid
secretion, pyloric sphincter contraction. S cells are stimulated by food in the intestine.
VIP (2 mins): found in blood, nerves (where there is Ach generally). Stimulates intestinal secretion of
electrolytes, H20; relaxes intestinal smooth m (including sphincters), dilatation of peripheral blood vessels,
inhibits gastric acid secretion.
Somastatin: Pancreas (D cells) produce somastatn which inhibits gastrin, VIP, GIP, secretin; pancreas
excretion, gastric motility, gallbladder contraction, absorption of glucose, amino acids, TG. Stimulated by acid
in lumen.
GIP: K cells in the duodenum, jejunum produce GIP which inhibits gastrin, stimulates insulin secretion.

Liver
 There are large gaps between the endothelial cells in the walls of the hepatic sinusoids (Therefore, permeable).
100 000 acini: terminal branches of portal v, hepatic a, bile ducts. Blood from the acinus drains into the
periphery, hepatic v then IVC. Zone 1 (most oxygenated).
Extra-hepatic biliary duct, gall-bladder: lined by columnar cells, mucous glands, fibrous tissue, smooth m.
Portal venous pressure: 10mmHg. Hepatic a pressure 90mmHg. Hepatic venous pressure 5mmHg.
Intra-hepatic porta v has smooth m in the walls innervated by noradrenergic vasoconstrictor n fibres via T3-11
ventral roots, splanchnic n. Hepatic a vasoconstrictor by hepatic sympathetic plexus.
Severe shock: noradrenaline intra-hepatic portal constricts, portal pressure, blood flow through the liver is
quick, could be hepatic necrosis.

Function
Carbohydrate metabolism: galactose/fructose (from portal blood to liver) to glucose; gluconeogenesis,
glycogen storage.
Fat metabolism: carbs converted to fat for storage
Lipoprotein synthesis: cholesterol synthesis (over-production gets converted to bile acids), albumin, clotting
factors
Detoxification: Kupffer cells trap and degrade bacteria (into less lipophilic metabolites, then excreted into bile
for excretion) with cytochrome p450 enzymes (oxidation/other reactions then esterification) which are
expressed in hepatocytes. Therefore, steroids are broken down quickly.

Bilirubin metabolism
Hb breakdown bilirubin- most bound in albumin. Otherwise, free bilirubin enters liver cells via OATP
(transporter), becomes bound to cytoplasmic proteins. UDP Glucuronyl transferase (endoplasmic reticulum)
conjugates it to glucuronic acid, glucuronide (more H20 soluble). It is then actively transported by MRP-2 into
the bile canaliculi. Small amount escapes into the blood, bound less tightly than bilirubin then excreted in
urine.
Urobilinogen: bacteria breaking down bilirubin. Intestine reabsorbs urobilinogen, some bile pigments.
Jaundice: due to free or conjugated bilirubin accumulation. Due to:
o Free bilirubin:
bilirubin: haemolytic anaemia
bilirubin uptake in the hepatic cell
Problems with conjugation
o conjugated bilirubin:
Problems with bilirubin secretion into bile canaliculi
Intra-hepatic/extra-hepatic bile duct obstruction
Ammonia metabolism

Ammonia (from colon, kidney) can cross blood-brain barrier (toxic). Kreb cycle (only liver): ammonia urea
(excreted in urine). Hepatocytes convert ammonia (mitochondira important) into cirulline, converted to urea,
removed by kidney.
Biliary system
Bile ducts are lined with columnar epithelium (cholangiocytes), with tighter junctions compared to liver,
though permeable- bile is isotonic.

Digestion
 Carbohydrates (mainly starch) digested by salivary, pancreas amylase. Further digestion by oligosaccharides in
the brush border of the small intestinal epithelial cells (derived by undifferentiated cells in the crypts of
Lieberkhn). When there is a deficiency in these oligosaccharides: diarrhoea, bloating.
Sugar and Na+ share the same co-transporter (Na-dependent glucose transporter). Na+ less intracellular,
therefore, moves inside the cell. Glucose follows and is released in the cell. Glucose gets transported in the
interstitium, capillaries via GLUT.
Protein digestion begins in the stomach. Pepsinogens (inactive protein enzymes) activated by the gastric acid,
become pepsin which break down peptide bonds. H pepsinogens= H gastric acid secretion. Therefore, when
gastric contents get mixed with alkaline pancreatic juice, pepsins dont work. Proteolytic enzymes in the
pancreas, intestine: trypsinogen (into trypsin by enterokinase); trypsin can conver other pro-enzymes into
active enzymes. Protein absorption most in the duodenum and jejunum.
For absorption, not only rely on Na+, sometimes Cl- dependant.
Fat digestion: mostly in duodenum as theres pancreatic lipase. Other minor factors when theres pancreatic
insufficiency: lingual lipase, stomach lipase (these pts have steatorrhea. Pancreatic lipase are activated by bile
acids. Fat + bile acids= micelles. Most fatty chains are absorbed in the colon.
Steatorrhoea: lipase deficiency, bile acid defective reabsorption (as in terminal ileum resection), hyper-gastric
acid secretion.
Vitamins: cant be synthesized. Fat soluble vitamins (D,E,A,K) are ingested as esthers, incorporated as
micelles (therefore, if no fat absorption as in low pancreatic enzymes, or bile duct obstruction, not much
vitamins absorbed), digested by cholesterol esterase, absorbed. Most are absorbed in the upper small intestines,
but Vit B12 (binded to IF (produced by parietal cells), VitB12-IF complex absorbed in ilium). Vit B12
absorption, folate absorption is Na + independent. H20-soluble vitamins: thiamine, riboflavin, niacin,
pyridoxine, ascorbic acid; are absorbed by Na+ co-transporters.
Fe: M pts loses it in stools, F pts loses it in menstruation. Ingested as Fe3+, absorbed as Fe2+. Gastric
secretions dissolve Fe (therefore, gastrectomy Fe def anaemia), Fe forms soluble complex with ascorbic
acid, all Fe absorbed in duodenum. Most Fe in Hb, then myoglobin, ferritin.

Clinical correlation
Short gut syndrome: when >50% small intestine is resected. Malabsorption occurs.
Terminal ileum resection: bile acid absorption (therefore, fat absorption, fat- soluble vits D, E, A, K).
Diarrhoea (unabsorbed bile acids enter colon, activate Cl secretion). Also, Ca2+