DIGESTION

GIT structure
GIT= tube along the length of body
o Lumen= central cavitity
Communicates with external environment
o At both ends
Two lines of development
o Growth
o Differentiation
Growth of GIT
Length in adult= 4.5m
Length in cadaver= 9-10m
o Dead= all muscles relax
Internal surface= 200-250 m2
o This is 600 x the surface area of outer surface
Differentiation of GIT
Mouth, esophasgous, stomach, small intestine, large intestine,
anus
Gut wall structure (mid-esophagus to anus)
Serosa: thin, tough layer of connective tissue
Muscularis externa: out layer of LONGITUDINAL fibers and inner
layer of CIRCULAR fibers
o Above 1/3 of esophagus + external anal sphincter=
striated
o The rest is smooth
Submuscosa: loose connective tissue, nerves, blood vessels,
lymph
Mucosa: 3 layers of tissue
o Muscularis mucosae (smooth muscle)
o Lamina propria (loose connective tissue)
o Epithelial layer (secretory and absorptive)
GIT functions
Motility (muscular activity) propulsion and physical breakdown
Secretion (mostly exocrine, some endocrine) chemical
breakdown
Absorption transfer to blood circulation
Digestive/absorptive efficiency
Carbohydrate 99%
Fat 95%

DIGESTION

Protein 92%

Gut wall innervation (ENS)

Consists of:
o Myenteric plexus (between longitudinal & circular muscle)
o Submusocal plexus
This function unit has all elements for reflex arc
o Sensory, effector and interneurons
Excitatory: release Ach on muscarinic
o Blocked by atropine
Inhibitory: release NANC (non adrenergic non cholinergic)
o Included peptides, purines, nitric oxide
Autonomic innervation of GIT
Synapse with enteric innervation (NOT muscle)
o Long, extrinsic reflexes
Parasympathetic (excitatory)
o Preganglionic (mostly vagus nerve X & pelvic nerves) from
medulla
o Release ACh on nicotinic
Sympathetic (inhibitory)
o Postganglionic from spinal cord (thorasic, lumbar) and
synapse in celiac, superior mesentertic, interior mesenteric
ganglion
o Release Noreadrenaline on noreadrenaline receptors
Sensory neurons go to CNS (more afferent to CNS than efferent
from CNS)

Hormone regulation of digestion

Non-GIT: growth and development
o Thyroid, GH
GIT: influence other activities
o Ghrelin: from stomach, stimulates hunger
o Leptin: from adipose
Influence food intake/metabolism
Induces satiety (decrease appetite)
GIT: on gut activity

DIGESTION
o Diffuse endocrine system (DES)
Endicrine glands are NOT in collections
o 5 GIT hormone: gastrin, CCK, secretin, GIP, VIP
Gut hormones (peptides)
Released from mucosa portal circulation (liver) systemic
circulation
Multiple targets: excitatory, inhibitory
Act with one another and neurotransmitters
o Synergistically (potentiate one another)
o Antagonistically
Propulsion in the GIT
Gradients of pressure
o Segmentation (mixing)
o Peristalsis (movement)
Variations in resistance: normally little/no resistance
Aboral= away from the mouth
Deglutition (swallowing)
Highly coordinated muscle movements to build pressure
Temporarily seal compartments to prevent dissipation of pressure
and DECREASE resistance
Phases: oral, pharyngeal, esophageal

Oral phase of deglutition

Anterior mouth pharynx
Initiate swallowing: voluntary cortex
o Can swallow (poor coordination) without
Coordinated movements: involuntary
o From deglutition center of medulla
Pharyngeal phase of deglutition (involuntary)
Protective reflexed initiated by afferent in pharyx medulla
o Passages into nose, moutn and trahea are blocked
o Apnea: temporary inhibition of breathing
Transfer to esophasgus
o UES (upper esophagus spinchter) relaxes
o Pharynx muscles contract

DIGESTION
UES

Closure: CNS vagus Ach on nicotinic= contraction

Relaxation: cessation of impulses= muscles relax

Pharyngeal phase summary

Involuntary
Rapid (1/5 second)
Stereotyped: same every time
Temporospatial coordination: 25 different muscles must contract
at the right time, strength
Esophagus
Body of esophagus lies within thoracic cavity
Exposed by negative pressure (-5mmHg -10mmHg)
o UES and LES separate the positive and negative pressures
Prevents aspiration
Striated muscle controlled by somatic vagus nerve
o ACh on nicotinic DIRECTLY on muscle
Smooth muscle controlled by vagus synapse on ENS
Esophageal forces
Gravity: increases rate of liquids
o NOT viscous solids
Peristalsis: generates pressure to push bolus down
o Primary peristaltic wave (every swallow)
8-10 seconds
Part of the deglutition reflexes
Control of esophagus
Afferent deglutition center
Efferent
o Striated: vagal motor neurons progressively
o Smooth: autonomic fibers read lower portion synchronously
Progressive delay in enteric neurons
If cut high up in the neck= NO primary peristalsis
If cut transthoracically: primary peristalsis continues
o THUS: vagus= initiation in proximal esophagus
o ENS= continuation and propagation in distal
Secondary peristalsis
Initiated by local distension
Mediated by ENS or vagal-vagal reflexes

DIGESTION

LES

Several secondary peristaltic waves may be generated

No visible enlargement of circular muscle
Half above (2cm) and half below (2cm) diaphragm
Muscle is contracted at rest (without innervation): myogenic
Release of NANC (ENS or vagus)= relaxation
o Part of deglutition reflexes

Hiatus hernia
NORMAL: increase in intraabdominal P increases pressure equally
on stomach and LES
HERNIA: LES is displaced into thorax
o Intraabdominal pressure increases DO NOT increase LES P
LES characteristics
Intrinsic physiologic sphincter (tonically contracted)
Anti-reflux mechanism assisted by intraabdominal segment
o Incompetent LES: sphincter fails to close
Heartburn (pyrosis)
Hormonal control of LES
Gastrin does NOT regulate contraction
Progesterone relaxes LES
o Pregnant: uterus causes hiatus hernia and progesterone
Both cause reflux
o Also in contraceptive pills
Motor functions of the stomach
Temporary storage: 1-2L
Physical disruption and mixing of contents
o Semi-liquid consistency= chyme
Regulates propulsion into duodenum
Stomach structure
Proximal: thin walled, for storage
Distal: thick walled, mixing and propulsion
Accommodation of a meal
Can accommodate from 50mL 1500mL
Receptive relaxation: increase volume without increasing
pressure
o Part of the deglutition reflexes
Vagus NANC ENS inhibit muscle tone

DIGESTION
From local distention (ENS or vago-vagal)
o If vagi is cut increase in intragastric pressure

Gastrointestinal peristalsis
From series of ENS in response to local distension
Starts at 1/3 of stomach
Magnitude of distension= amplitude
Electrical characteristics of smooth muscle= frequency
Called antral systole: chyme squirted back to stomach
Myogenic properties of the stomach
Proximal region: steady resting membrane potential
Distal: BER/ECA (basic electrical rhythm)
o 10-15 mV for 1-4 seconds at regular intervals (20s)
o Slight delay as you move down
o ALWAYS present independent of innervation
o Frequency= 3/min
o Origin= interstitial cells of cajal
ERA: Electrical response activity= CONTRACTION
o Always at peak of BER depolarization
o Number of spikes= amplitude
o Stimulus= ACh (local release) and stretch
Pyloric sphincter
Functionally insignificant
Open at rest, closed by antral peristalsis
Narrow lumen (<1 mm), behaves as filter
Emptying of liquids
Emptying proportional to pressure difference between proximal
stomach and duodenum
Normally, pressure difference is small
CUT vagus to proximal: Larger pressure gradient
o Liquids go faster
Cut distal stomach: solids move slower

DIGESTION

Gastric emptying of solids

Fundic (proximal stomach) reservoir
Antral (distal stomach) pump
o Frquency= 3/min
o Stroke volume: fluidity of chyme and amplitude of
contraction due to distension
Factors controlling antral peristalsis
Distension (increase activity)
o Stretch of muscles ERA
o Local ENS reflex: ACh= ERA
o Vago-vagal
Enterogastric reflex (decrease activity)
o Distension of small intestine
o Acidic (<3.5) chyme
o Hypertonic solution
o Too many fats, proteins, carbohydrates
Enterogastrone hormonal complex (decrease activity)
o Above conditions= secretin, CCK, GIP, VIP, neurotensin
Vomiting stages
Nausea
Retching: abrupt, uncoordinated respiratory movements with
glottis closed
Emesis: deep breath, closes glottis, contracts abdominal
muscles, exert pressure on gastric contents.
o Diaphragm is displaced upwards
o Upper GIT have no contraction (only lower stomach and
upper duodenum)

Control of vomiting
CTZ (chemoreceptor trigger zone)
o Outside blood brain barrier
o Response to circulating emetic agents
Vomiting center: close to medulla
o Coordinates vomiting

DIGESTION
Upper small intestine functions
Neutralization
Osmotic equilibrium
Digestion
Absorption
Motor activities of small intestines
Effective mixing
Slow propulsion (2-6 hours)
Intestinal contractions controlled by
Frequency: governed by BER (ECA)
o Frequency is higher in upper duodenum (12/min)
Progressively declining to 8/min
ERA (spikes): initiated by stretch of ACh
o # of ERA= amplitude of contraction
Proximal SI vs. distal SI
Frequency of BER is greater
Excitability if greater
Thickness is greater
THUS: frequency and amplitude of contractions is greater in
proximal small intestine

Intestinal contractions
Mixing: segmentation
o More contractions proximally= net aboral propulsion
Peristalsis: infrequent, irregular, weak, shallow
o Only travels for short distances (few cm)
o Pathological conditions: peristaltic rushes
The law of the intestine
Stimulus= radial stretch
ENS stimulated
Ahead of bolus= contract longitudinal, relax circular
Behind of bolus= contract circular, relax longitudinal
Colon motility

DIGESTION

After

Like SI but slower, sluggish, irregular

o Segmentation and peristalsis governed by irregular BER
Digestion and absorption is completed in SI
o Some H2O and ions still to be absorbed
Functions
o Mixing: to promote absorption of water and ions
o Propulsion: slow (50-60h)
o Storage
intake of a meal= stimulus
Gastroileal reflex= SI LI (stimulus=stomach)
Gastro colic reflex= LI rectum (stimulus= stomach)
Ileocolic reflex: reinforce in distal LI (stimulus = increased activity
in distal LI)

Interdigestive period
Pattern of cyclic myoelectric (motor) activity
Recur at regular intervals (~90 min)
Move from distal stomach SI distal ileum (~2-10 cm/min)

MMC (migrating myoelectric complex) phases

Phase I: no spike potentials, no contractions
o 60 min
Phase II: irregular spike potensias and contractions
o 20 min
Phase III: regular spike potentials and contractions
o 10 min
MMC

controls
Only in the distal stomach and the SI
Initiation= ENS: periodic activation of pattern generating circuitry
Propagation: ENS with modulation via ANS and gut peptides
Interruption= intake of a new meal

MMC functions
Housekeeping: cells destroyed and shed into lumen, bacterial in
SI from colon, fibers swept to the colon
Emptying of large non-digestible particles
o During MMC sphincter stays open
Process of digestion

DIGESTION

Sequence of interdependent steps

Enzymes are proteins
o Enzymes are then digested also
Duplication of enzyme activity along the GIT
Medium requirements: pH, ions

Secretion
Energy dependent
Blood flow dependent
Release fluid of ions and enzymes
o Amylase (carbohydrates)
o Protease (proteins)
o Lipases (lipids)
Pattern of regulation

Major salivary glands

Parotid: watery (serous) fluids
Sublingual: viscous (mucous) fluids to lubricate bolus
Submandibular: both serous and mucous
Mucous lining oral cavity produces very small volume

Saliva
Volume: 0.5-1.5 L/day
Ions: Na, K, Cl, HCO3 (same as blood)
o Hypotonic solution (only one)
pH: 6.5-7.0 (optimal for ptyalin)
o Starch (polysaccharides) + ptyalin= maltose
(disaccharides)
Some mucin, lipase (?), lysozyme (kill bacteria)

DIGESTION
Regulation of saliva (efferent)
ANS (NO hormones)
Parasympathetic
o ACh on muscarinic (blocked by atropine)
o Increase secretion of saliva
o Vasodilation
Sympathetic
o Vasoconstriction
Regulation of saliva (afferent)
Eyes, nose, etc higher centers salivary centers in medulla
o NOT in children
Sensory receptors in mouth salivary centers in medulla
Phases of saliva secretion
Cephalic (head)
o Psychic: conditioned reflex
o Gustatory: food in mouth
Gastric/intestinal: food is hot or irritating
Mixed gastric juice
1.5-2 L/day
Isotonic fluid: Na, K, Cl, H
pH= 1-2
pepsinogen: precursor or protease
Intrinsic factor: to digest vitamin B12
o Only secretion from stomach that is essential
Mucin: more than anywhere else in GIT
o Layer (1-2mm) covering the stomach
Mucin
Mucous, alkaline fluid
Secreted by all surface epithelial cells
ALSO secreted by tubular glands in the cardia and the antrum
Gastric glands in the fundus and corpus
Parietal (oxyntic) cell HCl
o Intracellular channels (canaliculus) lots of surface area
inside
o Lots of mitochondria
Chief cells pepsinogen
Mucus neck cell mucin

DIGESTION

Parietal cell secretion

Acid secreted across canalicular membrane against
concentration grad
o Isotonic HCl: 150 mEq H+, 150 mEq Cl For every H+ released into lumen HCO3 secreted into plasma
o Blood flow from stomach is alkaline
3 critical enzymes
o Carbonic anhydrase
o H/K ATPase
If inhibited= no H+ secreted (for ulcers)
Proton pump inhibitors
o Na/K ATPase
Maximum rate of secretion and pH is proportional to the number
of parietal cells
pH=0.8 (pure HCl)
Scheme for HCL secretion
Cl transported across canalicular membrane (into cell)
H+ available from dissociation of intracellular water
o Actively pumped into canaliculi in exchange for K+
Secretion of H+ leaves excess OH- in cell
o Co2 diffuse into cell
o CO2 + carbonic anhydrase= H2CO3
o H2CO3+OH-= H2O and HCO3o HCO3- diffuses into circulation
Functions of HCl
Precipitates soluble proteins
Denatures proteins
Activates pepsin and provides optimal pH for its activity
Chief cell secretion
Pepsinogen + HCl pepsin with the help of other pepsin
(autocatalysis)
Protein + pepsin= polypeptides when pH=2-3
Intrinsic factor
Only secretion of the stomach that is ESSENTIAL for life

DIGESTION

Glycoprotein
Secreted by parietal cells
Required for absorption in distal small intestine (ileum) of vitamin
B12

Gastric mucosa- protection

Muci-bicarb layer: first line of deference
o HCO3- and mucin
Gastric mucosal barrier (GMB)
o Apical surfaces and tight junctions
o Prevent any remaining H ions from entering
o ONLY found in the stomach
Rapid cell turnover
Ulcers
Normal HCl output but weak barrier
o Aspirin & NSAIDs: destroy GMB
o Helicobacter pylori: microorganism which buries itself
through the layer and secretes toxins that destroy
epithelial cells
Normal barrier but excessive HCl
o Cause duodenum ulcers
o Gastric producing tumors in the pancreas
Regulation of gastric secretions
ANS: sympathetic, vagus
Hormones: gastrin (from antrum), histamine (from throughout
the stomach), SS
Phases of gastric secretion
Cephalic: psychic, gustatory
Gastric
Intestinal

Neural regulation of gastric secretion

Cephalic phase
o Distension= ENS
o Vagus activates ENS
o Sympathetic inhibits ENS
Gastric phase

DIGESTION

o Distention= ENS
o Vago vagal reflexes
Intestinal phase
o Factors that control antral peristalsis also inhibit gastric
secretion

Hormonal regulation of gastric secretion

Gastric phase is mostly hormonal
Secretagogues= amino acids/partially digested proteins
o In the distal stomach
o Stimulate release of gastrin parietal cells
Gastrin also stimulated by ENS and vago-vagal in the
cephalic phase
Intestinal phase: secretagogues release gastrin-like hormone
more MORE HCl
o Factors that control antral peristalsis also inhibit gastric
secretion
Gastrin is self-regulating
+ feedback: more HCl= more secretagogues= more gastrin
- feedback: more HCl= pH less than 2= inhibit G cells from
producing gastrin
Histamine
Constantly release and presented to parietal cells
o Sensitizes parietal cells to other cells
Blocking histamine (H2 blockers)
o Less sensitive to ACh and gastrin (less HCl)
Pre-intestinal changes
Reduced to semi-liquid consistency
Acidified
Limited digestion
o Some polysaccharides disaccharides
o Some proteins polypeptides
o Some lipids di-, monoglycerides, fatty acids
Upper intestine
Neutralization
Osmotic equilibrium
Digestion continues
Absorption begins

DIGESTION
Pancreatic juice
0.5-1.5 L/day
Isotonic: Na, K, Cl, LOTS of HCO2
pH=7.2-8.2
Enzymes: amylase,
protease, lipase
o 3g%
Amylase
Polysaccharides
disaccharides
At pH 7
Protease
Cannot activate
proenzyme in
pancreas because they will digest the pancreas itself
Trypsin inhibitor: prevents activation of trypsin until it enters the
small intestine
o Secreted by the same cells which secrete the proteases

Digestion of fats
Triglycerides fatty acids, di-mono- glycerides
Help from: pro-colipase (+ trypsin) colipase
o Bile salts (from liver)
Liver & biliary system
Liver= storage, synthesis, toxification, metabolic activity
o Produces bile and releases it into SI (same site where
pancreas)
Spincter of Oddi= closed during interdigestive period
Gallbladder= storage of ile during interdigestive period
Liver

bile composition
0.5-1.0 L/day but much LESS enters duodenum
Isotonic: Na, K, Cl, HCO3
Solds: bile acids (salts), bile pigments, cholesterol, phospholipids

Gallbladder functions
Concentrates solids actual capacity is only 50-100 mL
o 3% 10-20 %

DIGESTION

Reduces pH: 7.8-8.2 7.0-7.5

Increases viscosity

Bile salts
Synthesized in liver from cholesterol
Facilitate digestion of FAT/cholesterol by forming water solule
complexes with them
o Also with fat-soluble vitamins (A, D, E, K)
Reduce surface tension and stabiles emulsions
Micelle formation
Bile salt= amphipath= one water soluble surface, one lipid
Above certain concentration then aggregate
o Aggregation of bile salt= micelle
o Water soluble on the outside and lipid soluble on the inside
Fats get trapped inside
Enterohepatic circulation
Daily release into intestine= 15-20 g
o But bile salt pool=3.5 and daily synthesis =0.5g
>90% actiavely reabsorbed in distal ileum via portal blood
10% escape in the colon bacterial modification
o and some gets reabsorbed
Bile salt functions
intraportal role of bile salts
o Regulate heptic bile flow: + feedback: more BS returned=
larger volume secreted
o Regulate synthesis of new bile salts: - feedback: more BS
returned= less new BS synthesized
Intrahepatic functions
o Solubility of cholesterol increased by 2 x 10^6
o If cholesterol precipitates= gallstones
Intraintestinal functions
o Act as detergents and help form stable emulsions
o Assist in the transport from lumen into intestinal cell
Fat and fat-soluble vitamins A, D, E, K
Intracolonic
o Inhibit Na transport and H2O absorption
o Excess BS in colon= diarrhea
Pancreas solutions
Some cells: large volume of juice, rich in HCO3

DIGESTION

Some cells: small volume of juice rich in enzymes

Regulation of bile flow

Choleretics: cause liver to secrete more bile (eg// bile salts)
Cholagogues: cause emptying of gallbladder
Law of reciprocal activity
o Contraction of gallbladder= relaxation of sphincter of oddi
and vice versa

Intestinal
mucosa
Villi:
complete
digestion,

absorption
Crypts: fluid (succus entericus) secretion

DIGESTION
Succus entericus (small intestine secretions)
3 L/day
Isotonic: Na, K, Cl, HCO3
pH= 7.5-9

Villi cells
As cells migrate up to villus regions (3-5 days) they become
capable to synthesizing enzymes
Enzymes are not release in lumen (except enterokinase)
retains in the brush border of cells
o Disachharases (surcrase, maltase, lactase, isomaltase)
o Also: amylase, lipase, aminopeptidases, dipeptidases
Colonic secretion
Small volume
Alkaline: HCO3 (100-150 mEq/L), K+ (100-150 mEq/L)
LOTS of mucin
Regulation of intestinal secretions
Local enteric reflexes
Vago-vagal reflexes
Hormonal factors
Poo

50g solids, 100 mL water

30% bacteria
30% undigested fiber
10-20% lipids
10-20% inorganic matter

Absorption

DIGESTION

What: mostly reabsorption

o 80g proteins (50= enzyme, 30=cells)
o 7L of secretions
Where: small intestine, colon (water/ions)
o 50% surface area of SI can be removed and it would be ok
=Hyperplasia= more villi= more SA
o Blood flow to intestine= 1-2 L/min
o Lymph flow= 1-2 mL/min
o Mostly in duodenum/jejunum except vit12 and bile acids in
ileum
How: simple diffusion, facilitated diffusion, active transport,
pinocytosis, osmosis

Requirements for absorption

Digestion: enzymes, pH, ions
Site for absorption
Transit time
Co-factors, transporters
Fluid secretions/absorptions
2 L ingested
Secretions
o Salivary glands: 1.5 L
o Stomach: 2.5 L
o Bile: 0.5 L
o Pancreas: 1.5 L
o Intestine: 1 L
Absorptions
o SI= 7L
o Colon= 2L
Water absorption
Max capacity of SI= 15 L/day
Max capacity of LI= 4-5 L/day