THE DIGESTIVE SYSTEM

GIT

▪ The primary function of the gastro-intestinal tract is to move nutrients, water and
electrolytes from the external environment into the body’s internal environment
 GIT
▪ The food we eat requires breaking down. This is done by a number of powerful
enzymes

▪ Mass balance: 2 litres drunk per day, vs 7 litres of water, enzymes, mucus and
electrolytes into the GIT

▪ Infection – GIT is exposed to the environment, and covers an area the size of a tennis
court
 Digestion/Absorption/Motility/Secretion
▪ Digestion refers to the breakdown of food into units that can be
carried across the intestinal epithelium
Lumen Wall IF Blood
▪ Absorption is the transfer of substances from the GIT to the ECF
Food
Secretion
▪ Motility is the movement of substances through the GIT via muscle
contraction Digestion

Absorption

▪ Secretion refers to the transfer of materials like water and ions from
the epithelial cells and the ECF to the lumen

Motility
GIT Anatomy

• Mouth
• Esophagus (esophageal sphincter)
• Stomach
• Pyloric valve (gatekeeper)
• Small intestine (most digestion/absorption)
- duodenum
- jejunum
- ileum
• Large intestine (solid fecal production)
• Rectum
Mouth/Salivary glands
• Mouth has many muscles. Roof comprises of hard
and soft palate (the hard palate is the front part of the
roof of the mouth, and the soft palate is the back
part)

• Digestion begins with mastication to reduce food size

• 3 types of salivary gland secrete:

- Enzymes
- Mucus
- Water

• Amylase catalyzes the hydrolysis of starch to sugars

• Lipases catalyse the hydrolysis of fats

• Lubrication (aids swallowing)

Mouth/Salivary glands
• Each gland is a pair

• Acinus cells are responsible for saliva

production

• The parotid glands are the largest, but

only secrete a small proportion of the
oral saliva (but the most amylase)

• The submandibular glands produce both

serous fluid (fluid enriched with protein
and water) and mucus (70% total)

• Sublingual glands produce mainly

mucus
 Mouth/Salivary glands

• The salivary glands are innervated by both

arms of the autonomic nervous system

• Sympathetic nervous system is responsible

for “dry mouth” when nervous!

• ACh/muscarinic receptor = salivation

Esophagus
• Is a muscular tube that links the pharynx
and the stomach

• Food moves down the esophagus via

peristaltic contractions. Contains 2
sphincters. The sphincter at the bottom
of the esophagus prevents stomach
contents from escaping back up the
esophageal tract (reflux disease)

• Epiglottis (flap of cartilage behind the

tongue) directs food down the
esophagus and prevents food/liquid
from travelling down the larynx to the
lungs
 Swallowing Reflex
• Swallowing food is a complex process! Over 20 muscles involved in
swallowing.

• Both somatic (tongue etc) and autonomic (pharynx and esophagus)

nervous systems involved.

1) Tongue pushes food bolus to back of throat

2) Food bolus stimulates receptors in the oral pharynx that triggers the swallow
reflex
3) Tongue touches hard palate and blocks the oral cavity
4) Soft palate blocks nasal cavity
5) Epiglottis covers trachea
6) Food moves down the esophagus by peristalsis (wave of muscle contraction)

See https://www.youtube.com/watch?v=YQm5RCz9Pxc
Stomach
• Parietal cells in the gastric glands secrete HCl
into the stomach

• Pyloric sphincter is responsible for controlling

food entry into the duodenum

• Mucous cells for protection (foveolar cells)

• Fundus (stores gas from digestion)

• Pylorus is a muscular valve that regulates food

movement into the duodenum

• Gastric rugae increase surface area

 Stomach
Gastric pits and gastric glands secrete exocrine and endocrine substances

Exocrine
Mucous (mucous neck cells)
HCl and intrinsic factor (parietal cells)
Pepsinogen (chief cells)

Endocrine
Gastrin (G cells)
Somatostatin
 Stomach tissue layers

Gastric mucosa, submucosa,

muscularis externa and serosa are
the major layers.

Similar pattern of tissue layer

arrangement in the intestine.
 Stomach tissue layers
Mucosa
- secretions (epithelium)
- connective tissue (lamina propria)
- smooth muscle (muscularis mucosae)

Submucosa
- connective tissue
- nervous tissue (Meissner’s plexus;
sensory)

Muscularis externa
- movement of food (muscles are
longitudinal or circular)
- muscles stimulated by Auerbach’s plexus

Serosa
- connective tissue
Small intestine
• Most nutrient absorption occurs in the small intestine
(enterocytes; intestinal absorptive cells)

• Digestive enzymes secreted by epithelial cells,

hepatocytes and the pancreas aid in digestion, and
create a soup called “chyme”

• Goblet cells secrete protecting mucus

• Brunner’s glands secrete protecting alkaline mucus

(duodenum)

• Chyme contains water, ions, nutrients, and enzymes

• Large surface area (villi and crypts) facilitate nutrient

absorption

• Peyer’s patches – lymphatic tissue found in the ileum

 Small intestine
• Large surface area (plicae, villi, microvilli)
 Small intestine

• The epithelium of the villi (sing. villus) contain

enterocyte cells (absorptive cells of the
intestines), goblet cells and endocrine cells

• Connective tissue core containing capillaries

and a lacteal duct (lymph vessel)

• Microvilli cover the villi to increase absorptive

capacity
Large intestine

• Only approx. 1.5L enters large intestine/day

• Cecum is a blind ending pouch – in herbivores it

contains bacteria for breaking down cellulose,
but in humans this function has been lost

• Colon absorbs liquid from chyme to produce

solid feces

• Distention of the rectal wall initiates the

defecation reflex, and a stool is passed
Movement of intestinal contents
• Peristalsis is the contraction of muscles to proper food down the GIT (and mix food)
• Circular smooth muscles contract in sequence to propel food.
• Following contraction of circular muscles behind food, and relaxation of circular muscles in front of
food, the longitudinal muscles contract to push food forward

• Segmental contractions differ, and are predominantly for churning contents of the GIT, to
promote digestion and absorption. Predominates in the small intestine
 Gastrocolic reflex
• Movement (motility) of the GIT (stimulated by distension of the stomach)

• Contraction generated in the myenteric plexus and occur through the muscularis externa

• Peristalsis and segmental contractions (mixing)

• Tonic (long; minutes or hours) contractions – anterior stomach

• Phasic (short; seconds) contractions - posterior stomach and small intestine

• Pressure in rectum then stimulates defecation reflex

 Gastroileal reflex
• Movement (motility) of the GIT

• Stimulated by gastric peristalsis and presence of food in the stomach

• Results in peristalsis of the ileum, and opening of the ileocecal valve (allows emptying of
ileum into large intestine)
 Defecation reflex

• Intrarectal pressure activates receptors in the

rectum that stimulate the nervous system and
induce the need to defecate

• Contraction of rectal muscles

• Relaxation of sphincter

• Rectum shortens as the material is passed

into the anal canal, prior to defecation
 Pancreas
• Is a secretory gland (insulin, glucagon etc)

• Secretes bicarbonate to neutralise stomach acid/chime

• Secretes digestive enzymes (acinar cells)

- Trypsin/chymotrypsin (proteins)
- Lipases (fats)
- Amylase (carbohydrates)
- Other hydrolases

• Shares an opening with the common bile duct

• Some people have two ducts (main and accessory)

• The accessory duct (Duct of Santorini) opens into the duodenum

Gall bladder and Liver

• Liver cells (hepatocytes) secrete bile which is stored in

the gall bladder

• Bile is not an enzyme, and instead acts like a detergent,

in the emulsification of fats

• Emulsification is the breakdown of fat into smaller fat

droplets which the pancreatic lipases can then hydrolyse
into fatty acids and glycerol

• Bile is composed of:

- Bile salts (detergent-like)
- Bilirubin (waste products of haemoglobin degradation
- cholesterol
Gall bladder and Liver

• Bile salts are actually derivates of cholic acid and

chenodeoxycholic acid (steroid acids)

• Amphipathic
 Absorption - Carbohydrates

• Only monosaccharides are absorbed/transported

across enterocytes into capillaries
- glucose, fructose, galactose

• Digestion is therefore essential for absorption

• Complex carbohydrates (starch, glycogen) broken

down by amylase into disaccharides

• Disaccharides are broken down by

disaccharidases (maltase, sucrase, lactase)
 Absorption - Carbohydrates
Monosaccharides transported across apical membranes by sodium-glucose transporter (SGLT) (or
GLUT5; fructose) and baso-lateral membrane by GLUT2
 Absorption - Proteins
• Proteins are digested into tripeptides, dipeptides and individual amino acids by exo- and endo-
peptidases

• All 3 can be absorbed

 Absorption - Proteins
• Amino acids – transported using
sodium transporters

• Di/tripeptides can be moved across

the apical and baso-lateral
membrane by H+ transporters
(PepT1). Some are processed by
cytoplasmic peptidases

• Transcytosis – movement of intact

larger peptides across enterocyte
membranes. This may be one
mechanism of food allergy
development
 Absorption - Fats
• Fats are emulsified by bile

• Colipase (secreted by pancreas) displaces some bile salts, allowing access of lipase.

• Lipase remove 2 fatty acids from the triglyceride

• Phospholipids are digested by phospholipase. Cholesterol requires no processing.

• Fatty acids, monoglycerides, phospholipids, and cholesterol then form micelles

• The micelles contact the enterocytes and the fatty acids move out of the micelles and diffuse across the apical
membrane

• The triglycerides are then reassembled and packed into chylomicrons (ULD lipoproteins) in the SER

• Chylomicrons are then packed into vesicles and transported across the baso-lateral membrane

• Rather than entering the blood immediately, the chylomicrons enter the lymphatic system (lacteals)

• Supply various tissues with fat

 Absorption - Fats

Micelles release contents to

diffuse across enterocyte
membrane
Absorption - Fats
Enteric Nervous System

• Humans have 86 billion neurons in the brain

• C. elegans nematode has 302!

• Glial cells are responsible for metabolic and

structural support of neurons (including
making myelin)

• Ganglia are nerve cell clusters (house the

cell bodies) within the PNS
 Enteric Nervous System

• Has been described in humans as the “2 nd brain”

• This is because despite significant innervation of the ANS, it can act independently of the CNS.

• 2 ganglionic populations – myenteric plexus and submucosal plexus

- both populations have motor and sensory neurons
 Enteric Nervous System

Myenteric plexus has primary control over GIT motility

- contraction of the inner circular layer of muscle
- contraction of the outer longitudinal layer of muscle

Submucosal plexus is largely responsible for sensing the luminal environment and controlling
epithelial cell function (secretions)
- mechanical, thermal, osmotic and chemical stimuli (including amino acids, pH, fatty
acids, and glucose
- sensory/motor/secretomotor neurons
Enteric Nervous System

2 ganglion populations
 Enteric Nervous System
• Normal digestive function requires communication links with the CNS.

• These links take the form of parasympathetic and sympathetic fibres that connect either the
central and enteric nervous systems or connect the central nervous system directly with the
digestive tract.

• Through these cross connections, the gut can provide sensory information to the CNS, and the
CNS can affect gastrointestinal function.

• Connection to the central nervous system also means that signals from outside of the digestive
system can be relayed to the digestive system: for instance, the sight of appealing food
stimulates secretion in the stomach.
 Gastric secretion
• Secretion of acid into the stomach occurs before food even reaches the stomach

• The parasympathetic system is activated in response to stimuli (smell/taste/sight) via vagus

nerve
- acetylcholine, histamine, gastrin (parietal cells)

• Entry of food into stomach, and stomach “stretch” further increases acid secretion
- long reflex; CNS
- short reflex; myeneteric plexus
- peptides (broken down proteins) stimulate G cells of the pyloric glands to produce gastrin
- somatostatin release has an opposing effect

• Entry of chyme into the duodenum stimulates more stomach acid secretion
 Inhibition of gastric secretion
• Duodenum inhibits gastric secretion via enterogastric reflex

- via ENS
- via brain (inhibition of vagus nerve)
- via sympathetic neurons that inhibit stomach gastric secretions

• Duodenal cells also secrete cholecystokinin and secretin which inhibit gastric secretion but
stimulate gall bladder and pancreas (closes pyloric sphincter, and aids chyme processing in
duodenum)
 Microflora
• Hugely important – 60% dry mass of stools is bacterial

• For every 1 human cell, there are 10 bacterial cells in your body

• Large intestine is the most important sink

• Important for:
- breaking down dietary fibre
- protection against pathogens (such as C. difficile)
- vitamin synthesis
- metabolism of drugs
- neutralising bile acids

• Systemic antibiotics