Gut physiology:

Functions of the Gut:

1. Digestion:
2. Storage:
a. Movement of food into the small intestine is regulated by pyloric sphincter
3. Movement:
4. Secretions:
5. Absorption:
Transverse section of GI tract:
1. Mucosa:
a. Inner lining composed of columnar epithelium with villi, goblet cells and the inner get is
extensively folded (brush border)
2. Muscularis mucosa
a. Reduces lumen when contracts (thin layer of muscle)
3. Submucosa
a. Contains secretory glands, blood vessels and nerves (submucosal and Meissner’s plexus)
b. Submucosal plexus controls secretions
4. Muscularis
a. Layer of circular muscle on the inside and longitudinal muscles on the outside
b. Innervated by the myenteric plexus.
c. Muscularis cells are electrically connected and a stimulation with propagate through the
muscle creating a wave of activity (peristalsis)
d. Creates a syncytium
5. Serosa
a. Anchors the gut

The enteric nervous system:

-The gut has its two neurological control plexuses, they are stimulated by parasympathetic impulses
from the ENS – increased motility, sections and relaxes the sphincters (para = rest and digest).
Sympathetic activity is inhibitory (decreasing the above) fight and flight.
-local reflex can operate independently to regulate function
-ENS also interacts with the ANS to coordinate the GI activity
-information from chemoreceptors and stretch receptors communicate with the brainstem
-Post ganglionic fibres from the celiac ganglion innervate the oesophagus stomach and gall bladder
-submucosal ganglion = large intestine
-myenteric ganglion = colon and rectum
1. Myenteric plexus:
a. Controlling contractions of the gut (peristalsis)
b. Contains sensory motor and interneurons
c. Increases tonic contraction intensity of contraction rate and rhythmic contraction
2. Submucosal plexus:
a. Controls sections of the gut
b. Contains sensory motor and interneurons
c. Modulates intestinal absorption
-pelvic nerve innervates the lower descending colon and the rectum
-glossopharyngeal (9) innervates the salivary glands and stimulates salvation
Smooth muscle contractions of the gut:
1. Tonic:
a. Is partial contraction that may be sustained for a prolonged period
b. Minutes to hours
2. Phasic:
a. Cyclical contractions last a few seconds
b. Repeated cycles of contraction of much shorter duration
c. Waves of spontaneous depolarization known as slow waves – these vary depending on
the area but range from 3-12 seconds long
d. Must be de polarized and slowly works its way along the intestines
e. Slow waves are faster in the duodenum but slow in stomach
Functional movements in GI tract:
Both hormones and ANS influence peristalsis in any region of the gut
1. Migrating motor complex:
a. Between meals sweep food remnants towards large intestine – every 90min
b. Triggered by hormone motilin
c. Normally nervous system dominates the control of movement however with the MMC
hormones are the important factor
d. Motilin is pH sensitive; and helps move acid substance away from stomach
2. Peristalsis:
a. Move food between 2-25 cm/min
b. Contraction of bot circular and longitudinal muscle layers
c. Man propulsive movement (fastest in oesophagus)
d. Caused by a reflex when the muscle is stretched by a food bolus
3. Segmentation:
a. Moving movement involving 1-5cm of intestine
b. Predominantly in the small intestines
c. AIDs in digestion of food by mixing
d. In large intestine haustra = haustration which churns the food
e. AIDs in absorption of water and salts
f. Contraction of circular muscles and relaxation of longitudinal layer

GI reflexes: (involving the ENS

1. The enterogastric reflex:
a. When food is in the small intestine it suppresses the secretion and motility of the
stomach – with acid secretions the stomach contracts
b. Creates a a feedback response which decreases the sections of the gastric acid in the
stomach and more importantly reduces the frequency and intensity of peristaltic waves
in the stomach
c. Net result is slowing the passage of chyme from stomach into the small intestine
2. The gastrocolic reflex:
a. Distension of the stomach stimulates evacuation of the colon – prepare for more room
b. Creates the ‘wish to empty bowel’

Control of motility and secretions:

1. Main controls – ENS and ANS
2. Major controlling factor = hormone release (motilin)
Digestive hormones:
1. Gastrin:
a. Secreted by: G cells in the stomach antrum
b. Target: ECL (enterochromaffin-like) cells and parietal cells
i. Regulates the production of HCl from the parietal cells
ii. Somatostatin has a role in regulating gastrin
iii. When gastrin binds to ECL it increases the release of histamine
iv. Gastrin binds to a CCKB receptor on the parietal cells
v. When gastrin works with ACH it brings on a second messenger mediated rise in
intracellular Ca++ causing the tubulovesicles to fuse with the cell membrane and
insert new H-K pumps (increases activity)
vi. Gastrin and CCK act to relax the fundus and enhance contraction in the body
and antrum of the stomach
vii. Gastrin stimulates gastric motility along with neural stimulations
viii. Gastrin also acts on the acinar cells to produce more enzymes (pancreas)
ix. Gastrin and secretin stimulate bile formation
2. Cholecystokinin (CCK)
a. Secreted by: endocrine cells of small intestine (duodenum) the I cell + neurones (brain
and gut)
b. Target: gallbladder, pancreas, gastric smooth muscles
i. Acts to relax fundus and enhance contractions in the body and antrum
ii. Stimulates acinar cells to secrete enzyme rich fluid
iii. Stimulated particularly by fatty foods in the duodenum
iv. Increases exocytosis of zymogen granules as rapid response (response to rise in
cytoplasmic Ca+++ second messenger mediated)
v. CCK and ACH relax the sphincter of Oddi and therefore increase pancreatic
outflow
vi. Stored bile is released when stimulated by CCK causing the gallbladder to
contract
vii. CCK and secretin inhibit secretion of gastric acid and reduce gastric motility and
slow gastric emptying (allowing for digestion to occur)
3. Secretin:
a. Secreted by: endocrine cells in the small intestine (duodenum)
b. Target: pancreas and stomach
i. Stimulate the secretion of HCO3 rich fluid from the duct cells
ii. Stimulated by acid in the duodenum (chyme)
iii. Produced by S type endocrine cells in the duodenal mucosa
iv. Secretin acts to neutralize acid by increased activity of HCO3/Cl- exchanged
and the CFTR channel
v. Both CCK and secretin inhibit gastric emptying and reduce gastric acid
4. Gastric inhibitory peptide (GIP):
a. Secreted by: endocrine cells in small intestine
b. Target: beta cells of endocrine pancreas
i. AIDs in decrease gastric motility and emptying
5. Motilin
a. Secreted by: endocrine cells in small intestine
b. Target: smooth muscle of the antrum and duodenum
 i. Most important factor in movement of the small intestine
6. Glucagon like peptide 1
a. Secreted by: endocrine cells in small intestine
b. Target: endocrine pancreas

Digestion and absorption:

1. Proteins:
a. Digested by proteinases to produce amino acids
b. In stomach protein is denatured then hydrolysed to peptides and amino acids by
hydrochloric acid.
c. Pepsinase pepsin begins breaking peptide bonds in the proteins
d. Pepsinogen is released by chief cells of the stomach
e. Peptide fregments move into the small intestine
f. Movement into the duodenum releases bile and pancreatic juices which contains
proteinases (trypsin, elastase, chymotrypsin, and carboxypeptidase)
g. These proteinases digest protein further.
h. Endopeptidase: degrease proteins by hydrolysing interior peptide bonds
i. Exopeptidases: hydrolysis one amainoacide at a time form the C terminus of proteins
and peptides
2. Fat digestion:
a. Most abundant dietary fats are triglycerides (cholesterol and phospholipids are
absorbed in a similar way)
b. Small intestine bile salts emulsify the fats to increase surface area
c. Pancreatic lipase digest triglycerides to free fatty acids
d. Digestion products form a Micelle which aids absorption
e. Once inside epithelial cell, triglycerides reform and combine with cholesterol and
proteins for transport to the liver
f. Products of lipase digestion are free fatty acids and 2 mono glycerides
g. Micelle formation aids in absorption of the lipids
h. In the cell the Micelle combines with other lipids and apolopoproteins to form a
chlyomicron – too large to enter blood supply so they enter lymphatic system and then
venous blood
3. Carbohydrate digestion:
a. Salivary amylase begins to hydrolysis starch and continues working for up to an hour
b. Pancreatic amylase (small intestines) breaks down carbs to mono and disaccharides
c. Disaccharideases in the brush border (surface of gut) Break disaccharides into mono
which can be absorbed into the small intestine
d. Only 3-5% of starch is digested by saliva – pancreatic amylase is more active
e. Monosaccharides are absorbed by specific carried in the small intestine:
f. Glucose polymers(starch, glycogen) -> disaccharides(maltose, sucrose, lactose) ->
monosaccharides(2 glucose, 1 glucose + 1 fructose, 1 glucose + 1 galactose)
g. Glucose polymers digested to disaccharides by amylase
h. Disaccharides digested to monosaccharides by maltase, sucrase, lactase
i. Monosaccharides(glucose/fructose/galactose) can be co-transported with Na+ gradient
j. Fructose uses GLUT 5 transporter
k. Glucose and galactose use Na+ dependent co-transporter SGLT1 and are then
transported into from the cell into the blood by GLUT2
Water and salt absorption:
 1. Water is passive and driven by osmotic gradient produced by salt absorption
2. Most water absorption = small intestine
3. 1.5L = colon
4. Membrane proteins transport Na+ ions into epithelial cells
5. Ion channels cause influx of ions into the epithelial cells
6. Na+ is then pumped into the blood by the Na/K ATPase pump causing NaCL movement into the
blood from the gut lumen – water is then drawn in due tot the osmotic pressure
7. This process is called osmosis
Vitamin absorption:
1. Fat soluble vitamins = small intestine along with fat digestion
a. A,D,E and K
b. E is specifically absorbed in the terminal ilium
2. Water soluble vitamins absorbed by specific carriers
a. Vitamin B (cobalamin B12): intrinsic factor from the parietal cels
i. Essential for RBC production in bone marrow
ii. B12 isn’t digested in the stomach due to R-B12 complex
iii. R-B12 complex is formed from R protein in the mouth
iv. R-B12 complex is split in the small intestine by pancreatic enzyme (bicarbonate)
therefore pancreatic diseases can result in B12 deficiency and anaemia
v. Crohn’s disease can lead to B12 disease as it affects the terminal ilium
b. Vitamin C: needs adequate amounts of Vit. D to be absorbed
i. Absorbed in the small intestine aided with Vit D
c. Iron: Fe2 = duodenum and proximal jejunum
3 phases of digestion:
1. Cephalic phase: before food enters stomach
a. Anticipation response (sight, smell, thought of food)
b. Medulla and parasympathetic efferent fibres increase saliva production
c. Vagal stim. Of the ENS causes secretion and motility in the stomach intestines and
pancreas
2. Gastric phase: distension of stomach by food
3. Intestinal phase:food enters duodenum
Secretion of saliva:
1. Acinar cells secrete isotonic fluid (high Na low K+)
2. Saliva is a hypotonic fluid high in K+ and HCO3
3. Ducts are impermeable to water which makes the solution hypotonic
a. Saliva = lysozyme (antibacterial) and immunoglobulins (antibodies IgA) + bicarbonate
ions and Ca which helps protect the teeth
b. Saliva = submandibular, parotid, and sublingual glands – 1L per day
c. Each gland secretes water, ions, amylase, mucous, mucin glycoproteins, lysozyme and
IgA
d. Sympathetic stimulation causes vasoconstriction which decreases the secretion of saliva
(indirect innervation of salivation)
e. Parasympathetic innervation from the facial + CN9 nerves cause vasodilation and
stimulate secretion
4. Aldosterone acts on ductal cells to increase the reabosption of Na+ (Same as in the renal
tubes)
5. Licking wounds can make them heal 10% quicker — cool shit
Sjogren’s Syndrome:
 1. Autoimmune destruction of exocrine cells in the salivary gland and tear ducts
2. Presents with dry mouth difficulty eating and speaking, dental caries and gum disease
3. Second most common autoimmune disease in the world
Achalasia:
1. Uncommon = a lack of peristalsis in the lower 2/3 of the oesophagus and failure of the lower
oesophageal sphincter to relax
The Stomach:
Muscular sac with layers of longitudinal and circular smooth muscles – fundus body and antrum.
1. Storage: roughly 1.5 L
2. Digestion: chemical and mechanically breaks up food to form chyme
3. Protection: acid environment is bactericidal but may damage the gastric lining if protective
barrier fails
4. Secretions: secretes acid, enzymes and gastric hormone (gastrin)
Cells of the stomach:
1. Mucous cells: thick sticky bicarbonate rich mucus which protects the stomach (pH of stomach
cells is 7.4 alkaline)
a. Buffer to stomach wall against gastric acid
2. Parietal cells (oxyntic): secrete hydrochloric acid (HCL) and intrinsic factor (B12)
a. Stimulated by ACH, gastrin and Histamine
3. Chief cells: inactive Pepsinogen – converted in the acid environment to Pepsin – also secretes
gastric lipase
a. Stimulated by Acetyllcholine acid and secretin
4. Endocrine cells:
a. G cells: synthesis of hormone Gastrin acts on parietal cells to make HCL
i. Stimulation: ACH, peptides, amino acids
b. ECL cells: make histamine which is used in acid regulation
i. Stimulation: ACH and gastrin
c. D Cells: make hormone somatostatin which acts to aid in the secretion of gastrin
i. Stimulation: acid in the stomach
Gastric Acid:
1. Gastric secretions = pH 0.8-1.0 (acidic)
2. H+ ions are pumped across a gradient which requires ATP hydrolysis

Parental cell activation:

1. Resting cells: tubulovesicles contain H+/K+ ATPase pumps which are closed
a. Receives its H+/K+ from the plasma – excretes into lumen
2. Active: cell opens up 50-100 fold and secretes acid into the lumen of the stomach
a. CO2 diffuses into the parietal cell from the blood (carbonic anhydrase
b. Cl/HCO3 exchange occurs
Regulation of acid secretions:
1. Increase in gastric pH (chemoreceptors)
2. Increase in peptide fragments in stomach
3. Distension of stomach wall (trigger for release of acids)
4. Irritant foods and stress (mechanoreceptors – Vagas nerve)
a. Chemoreceptors = rise in pH stimulates sensory nerves of the ANS and ENS -> stimulates
the parietal cells to secrete more acid
b. Caffeine, spices and peptide fragments stim more acid than other foods
c. Stretch receptors = mechanoreceptors -> vagus nerve = more acid
 5. Parietal cells respond to 3 physiological regulators
a. Acetylcholine
b. Gastrin
c. Histamine
6. Two things inhibit acid secretions:
a. Somatostatin
b. Prostaglandins
Indirect stim of acid secretion:
1. Acetylcholine, gastrin and histamine stimulate the parietal cell triggering the secretion of H+
into the lumen
Direct stim of acid secretion:
1. ACH and gastrin stimulate the ECL cell – results in section of histamine which acts on parietal
cells to secrete acid.
Parietal cells:
1. Secrete acid and intrinsic factor
2. Has receptors for ACH, gastrin and histamine on its inner cell membrane

Pathways to increase acid secretions:

1. ACH and gastrin = second messenger mediated rise in intracellular Ca++ = tubulovesicles to fuse
with the cell membrane = increased insertion of H/K ATPase pumps
2. Histamine: activates PKA (Protein kinase A) which phosphorylates the H/K pumps and increases
their activity
3. Prostoglandins and somatostatin bind to parietal cell to DOWN REGULATE acid production.

Peptic ulcer disease: REFER TO PAT********

Pharmacology of acid production:

1. Antacids neutralize gastric acid but can promote further acid production
2. H2 receptor antagonists (CIMETADINE RANITIDINE) block the histamine mediated increase in
acid production
3. Proton pump inhibitors (AMEPRAZOLE and IANSOPRAZOLE) directly block the H/K ATPase pump:
most effective class of drugs and act directly to bind to and block the pump – will block 90% of
acid production
Gastric motility:
1. Hormone and neural control
2. Gastrin CCK act to relax fundus and enhance contraction in the body and antrum (churn food)
3. Food in stomach increases acid and pepsin production -> gastrin and neural stimulation ->
gastric motility increases -> pancreatic sections increase
Gastroparesis:
1. Gastroparesis is delayed gastric emptying
a. Caused by anorexia, surgical damage to nerves and diabetes mellitus
b. Nausea vomiting and food can harden into a solid mass that may cause obstruction
Small intestine: duodenum, jejunum, ilium
1. Gets chyme from stomach + intestinal, pancreatic and hepatic secretions
a. HCO3 ions, bile, and digestive enzymes
2. Intestinal juice secreted from intestinal glands (crypts of lieberkuhn) -> stim. By stretch due to
food in intestine
3. Duodenum secretes enterokinase -> convert inactive pancreatic trypsinogen to active Trypsin
 4. Burners glands -> HCO3 -> neutralize acid chyme
Coeliac disease: PAT NOTES **********

Lactose intolerance:
1. Brush border anytime lactase is not produced in adulthood (why humans shouldn’t drink animal
milk… fucking WEIRD as MUHFUKERS)
2. When lactose isn’t digested it stays in gut as osmolyte which prevents water absorption
3. Gut bacteria metabolism the sugar and produce gas – shit your pants and stuff

Pancreas:
1. Exocrine + endocrine organ
2. Exocrine:
a. Pancreatic juice
b. Alkaline solution
c. Acinar cells:
i. Trypsinogen
ii. Chymotrypsinogen
iii. Procarboxypeptidase
iv. Proelastase
v. Prophopholipase nucluease
vi. Colipase
vii. Amylase
d. Duct cells:
i. Water and ions (HCO3)
3. Pancreas produces trypsin inhibitor to protect itself from the damaging effects it can have on
tissue
4. Pancreatic secretions have a pH of 6-8
Pancreatic anytime activation:
1. Proteolytic enzymes -> proenzymes and zymogens (inactive)
2. Activation of trypsin -> spontaneously due to enterokinase (produced by duodenum brush
boarder)
3. Trypsin activates the other proenzymes
4. Premature activation of enzymes in the pancreas = death of pancreas.
Bicarbonate secretions (HCO3):
1. Pancreatic duct cells -> high levels of carbonic anhydrase
2. Bicarbonate exchanged for chloride and protons exchanged for sodium in pancreas duct cells
3. Bicarbonate is buffer system in the blood and stomach .. basically whole body.
4. Chloride ions recycle -> exchange for bicarbonate in the apical membrane through CFTR channel
(important in Cystic fibrosis)
Cystic fibrosis:
1. Most common human genetic disease – mutation of CFTR protein
2. CFTR is a chloride channel found in epithelial cells at many location -> pancreas, lungs, salivary
glands.
a. Defects = thick mucus which clogs the airways, intestines, pancreatic ducts.
b. **Failure of chloride movement out of the duct cells then bicarbonate secretions will
fail and more importantly because the osmotic gradient is not maintained water does
not enter the lumen – mucus cells are still secreting so the result is a thick viscous
mucus which blocks the pancreatic ducts**
 i. New born blood spot test, sweat tests genetic test.
Control of pancreatic secretions:
1. 3 hormones and vagal activity:
a. Secretin:
i. Stim duct cells -> bicarbonate
b. Chelecystokinin(CCK):
i. Stim acinar cells -> enzyme rich fluid (as above)
c. Gastrin:
i. G cells -> stim acinar cells -> enzyme rich fluid
d. Vagal activity:
i. ACH from PNS and ENS stimulate enzyme production by acinar cells
ii. Mediated by ACH binding to muscarinin receptors
iii. CCK and ACH relax the sphincter of Oddi and therefore increase pancreatic
outflow
iv. Stim acinar cells -> anzyme rich fluid
Pancreatitis:
Acute Pancreatitis:
Chronic Pancreatitis:

Bile and the Gall bladder:

1. Store and concentrate bile that the liver makes and deliver to the gut (ampulla of vater)
2. Bile mixes with food and aids in absorption of fat and certain vitamins
3. Emulsifiers fat and aids its digestion and absorption in small intestine
a. Bile from the liver can go directly to duodenum or be stored in gallbladder
b. Storage -> cystic duct
c. Duodenum -> common bile duct
Bile composition:
1. Bile salts:
a. derived from cholesterol
2. Bilirubin:
a. Breakdown components of haemoglobin – waste product
b. Very toxin
3. Cholesterol:
a. Excess is secreted in bile
b. Not very water soluble – not secreted in urine
4. Drugs:
a. Metabolized by liver and secreted in bile (biliary excretion)
Liver can produce up to a liver of bile a day
Actions of bile salts:
1. Amphipathic (hydrophobic and hydrophilic parts)
2. Polar side chains interact with water – hydrophobic part binds to fat (lipid droplets)
3. Break down fat globules making pancreatic lipase enzyme work on the rest
4. Present smaller fragments from coalescing into large globules again and keep fat suspension.
Bilirubin:
1. Formed from Haem (in spleen during haemolysis)
2. Bound to albumin for transport into the liver
3. Conjugated to glucuronic acid to increase its solubility and make it easier to excrete
4. Only conjugated bilirubin can be excreted (pats for more info)
Conjugation of Bilirubin:
1. Enzyme UDP-glucuronosyltransferease (UGT) transfers molecules of glucuronic acid to bilirubin
in the liver
2. Breakdown of RBC in spleen
3. Transport to liver bound to serum albumin
4. Bilirubin conjugated with glucuronic acid
Bilirubin and jaundice:
1. Occurs when excess amounts of bilirubin accumulates in the liver (increased haemolysis,
blockage of cystic duct/common bile duct, fatty alcoholic liver disease)
2. Excess bilirubin binds to tissues (skin, eyes, sclera) giving yellow appearance
3. Commonly occurs in premature babies – if not treated – kernicterus occurs (brain damage)
4. Treated with UV light-> can cause bilirubin to immersive to a more soluble form which can be
excreted more readily
Crigler-Najjar syndrome:
1. Rare genetic disorder caused by absence of bilirubin conjugating enzyme (UGT1A1)
2. Untreated in infants -> kernicterus (bilirubin induced neuropathy) **** exam Question
Gilbert’s syndrome:
1. Common disorder -> less enzyme activity -> harmless jaundice
Control of Bile section:
1. Liver produces 600-1000ml/day
2. Gallbladder stores 60ml
3. Bile is concentrated and storage and water is added back as it is secreted
4. Formation of bile is stimulated by secretin and gastrin ** EXAM Q.
5. Release of stored bile is stimulated by CCK which causes gall bladder contraction* EXAM Q.
6. Fatty chyme – CCK stim to release gallbladder bile + parasympathetic stimulation causes the
sphincter of Oddi to relax and allow bile and pancreatic juice into the duodenum
Gall stones: ** PATS NOTES
1. 94% of bile salts are reabsorbed
2. Reabsorbed through active transport From ilium
3. Enterohepatic circulation:
a. Reabsorption from distal ileum
b. Reabsorbed bilirubin -> blood -> liver
Enterohepatic circulation:
1. Liver -> common bile duct/gall bladder -> duodenum -> distal ilium -> portal circulation -> liver.

Intestinal phase:
1. Chyme in duodenum -> secretions from pancreas + gallbladder (stim by CCK secretin and neural)
2. CCK and secretin also inhibit gastric acid secretions from parietal cells + decrease motility and
slow gastric emptying (absorption can occur)
3. Enteric nervous system activated to slow gastric mobility (rest and digest)
4. GIP (gastric inhibitory peptide): produced by small intestine contributes to decrease gastric
motility and emptying
The Large Intestine:
1. Storage, secrete mucus, absorbs water and salts, absorbs vitamins, secretes bicarbonate,
secretes potassium
a. Acute diarrhoea = loss of large amounts of bicarbonate = metabolic acidosis
b. Acute diarrhoea = loss of potassium = hypokalemia
 2. 3-4 times a day -> large gastric movements caused by gastrocolic reflex
3. Defecation reflex initiates the need to poop (everyone poops..) it is then under voluntary
control.

The Liver:
1. Regulation of metabolism
2. Synthesis of plasma proteins and lipoprotein carriers
3. Production of bile
4. Detoxification of ammonia (amino acids -> urea)
5. Drug and hormone metabolism
6. Formation and destruction of RBC (stores iron and Vit B12)
7. Liver regeneration is possible as the hepatocytes acute as stem cells – 1/4th a live can grow into a
full liver again.
Hepatic circulation:
1. At rest liver = 25% of cardiac output
2. 400ml/min
3. Nearly everything absorbed in gut goes straight to liver.
4. Aorta -> abdominal aorta ->
a. Hepatic artery -> liver -> hepatic vein -> IVC -> heart
b. Digestive tract arteries -> hepatic portal vein -> liver -> hepatic vein -> IVC -> Heart
5. Venous blood from the spleen, pancreas, small intestine and large intestine (largest supply of
blood to liver)
Liver and metabolism: plays a role in all three metabolic pathways
1. Carbohydrate:
a. Stores glycogen and synthesis glucose by gluconeogensis
b. Liver = target tissue for insulin -> majority of glucose/gluconeogensis there – insulin
regulates
c. 60% of ingested glucose is immediately taken up by the liver and converted to glycogen
2. Protein:
a. Delaminates excess dietary amino acids so they can be used as energy source
b. Amino acids -> bluconeogenesis -> glucose
c. Carbon components are used for gluconeogenesis
d. If transaminase enzyme breaks down AA = ammonia = highly toxic
3. Fat:
a. In excess – liver releases triglycerides into the blood so it can be stored else where in the
body
b. In deficit the liver converts fatty acids to carbon intermediates that can enter the TCA
cycle in other tissues
c. Liver also stores fat soluble vitamins (ADEK) – AH DUNT EveN KnOw (IDEK)
Synthesis of plasma proteins and Lipoprotein carriers:
1. Liver synthesises all the plasma proteins (except immunoglobulins -> plasma cells)
2. Osmotic pressure depends of plasma depends on plasma protein concentration
3. Many hormones and metabolites are not water soluble -> must be carried by carrier proteins
4. Albumin is essential for bilirubin transport – 60% of PP in liver = serum albumin
5. Clotting factors and hormone carrier proteins also produced in liver
6. Lipoproteins are needed for cholesterol and triglyceride transport
Detoxification of ammonia:
1. Ammonia is produced when Amino acids are broken down for energy else where in the body
 2. This results in deamination into ammonia (NH3) and Carbon + Hydrogen
3. Carbon and hydrogen are used in gluconeogensis
4. Ammonia is toxic and must be disposed of properly
5. Ammonia if bound to CO2 to produce Carbamoyl phosphate
6. Carbamoyl phosphate binds with ornithiine to produce Citrulline
7. Citrulline binds to aspartate to form argininosuccinate
8. Argininosuccinate is phosphorylized to fumarate which is disposed of and arginine
9. Arginine is bound to H2O to produce Urea (H2N-C-Nh2=0)
10. Urea can be excreted more easily and without excessive toxicity
Drug and hormone metabolism: Liver
1. Liver metabolises and/or conjugated many drugs to inactivate them and render them more
WATER SOLUBLE
2. Many hormones are inactivated by mechanisms in the liver
3. Both endogenous and pharmaceutical agents will be carried to the blood to the liver and be
destroyed or modified for excretion
4. Two man methods of detoxification:
a. Transformation: rendering the drug ineffective -> excrete
b. Conjugations: bind with another molecule to make it more soluble and easier to excrete

Formation and destruction of RBC:

1. Average life of RBC = 120 days
2. Senescent cells are destroyed by Macrophages in the liver, spleen and lymph nodes
3. Iron from haem group is stored in the liver and reused (erthyropoesis)
4. Vit B12 and Vit A are stored in the liver
a. B12 = essential cofactors for anzymes in the metablolic pathway which produces haem
b. Vit A = essential for correct retinal development and vision (deficiency = blind)
5. Consequence of liver failure
a. Severe hypoglycaemia
b. Malnutrition and vit. Deficiency
c. Oedema (ascites)
d. Impairment of blood clotting
e. Neuropathy
f. Increased response to administered drugs
g. Endocrine disturbances (angiotensiogen – angiotensin 1
h. Anaemia
i. Jaundice
6. Advanced liver disease = symptoms of neuropathy (peripheral and central)
7. Prolonged drug life
8. Hormonal disturbances
9. Jaundice and kernicterus in infants
Gut Immunity: Gut associated lymphoid tissue (GALT)
1. Surface of gut represents a huge area of contact between outside world and the body interior
2. Large potential for microbial pathogens, viruses, and intestinal parasites
3. Mucus, digestive enzyme and acid all create a bacterial environment
4. GALT: largest collection of lymphoid tissue in the body – also large colony of Lymphocytes
a. 80% of all lymphocytes are found in the small intestine
5. Factors contribute to GALT:
a. Immune cells
 b. Immune cell clusters (peyers patches) lowest part of the small intestine (ileum)
c. Lymphoid (B and T and macrophages) in the patches and overlaid with M cells
(microfold cells)
d. M Cells pass information about gut immunity to the contents of the GALT
6. Peyers patches:
a. Similar to lymph nodes
b. M cells have surface receptors that bind foreign antigens and transport them into the
interstitial fluid
c. Macrophages and lymphocytes in the interstitial instigate an immune response
i. Secrete cytokines (attract immune cells)
ii. Trigger inflammatory response
iii. Promote increased mucus production
d. Assist in antigen presentation
e. M-cells (transcytosis) pass information to the immune cells to activate them
f. Common pathogens carried by M cells are:
i. Shigella
ii. Flexneri
iii. Salmonella
iv. Typhimurium
v. Yersinia
vi. Pseudotuberculosis
Inflammatory bowel disease:
1. Affects the colon but can also appear in the small intestine
2. Examples: IBD, ulcerative colitis and Crohn’s disease
3. Treatment = steroidal anti-inflammatory drugs which inactivate cytokines

The end