Digestive system

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 Main function provide body with nutrients through performing the followings
Movement , Secretion, Absorption, Portal circulation, Control by nervous & hormonal mechanisms

Intestinal barrier function

A- Mucosal surface = columnar epithelium→ Forms semipermeable barrier →
for absorption of nutrients & Prevents crossing of pathogens
B- Dysfunction of barrier →cause inflammatory conditions in the GIT.

GIT immune system

A- Mucosal immunity = Largest immune system in GIT, formed of
Organized lymphoid tissue T lymphocytes between enterocytes Lymphoid tissue in lamina propria
as tonsils, adenoids forming intestinal barrier, mainly formed of T and B cells, plasma
cytotoxic T cells cells
B- Gut microbiota
C- Dysfunction of mucosal immunity and/ or microbiota (dysbiosis), → cause dysfunctions in various systems
Basic Electrical Activity of GIT Smooth Muscle
1. The slow waves: (Basic Electric Rhythm) = (BER)
Definition
o Slow changes in RMP, in smooth muscles of GIT (except in esophagus and proximal part of stomach)
o In the form of spontaneous depolarization & repolarization from -65mv to -45mv
Frequency: determines the frequency of contractions in each segment
• 4/min in stomach, 12 in duodenum, 8 in ileum.
• 2 in cecum , 6 in the sigmoid colon
Cause Initiated by interstitial cells of Cajal $
Importance: Not causes muscle contraction
Allows smooth muscle to generate spike potentials
interstitial cells of Cajal (ICCs)
Function: pacemaker cells →generates slow waves in smooth muscle fibers
Site: In stomach & small intestine→ in outer circular muscle
In colon: inner circular muscle at submucosal border
2.The Spike Potentials:
Definition True action potentials
Cause Depolarization is due to Ca++ influx, repolarization is due to K+ efflux.
Importance cause contraction due to entry of calcium.
• Acetyl choline →↑number of spike potentials
• Epinephrine: vice versa

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Regulation of gastrointestinal functions
A-Nervous regulation = Innervation of the GIT:
1. Intrinsic innervation = Enteric Nervous System (independent)

2 neural plexuses 1- Myenteric (Auerbach's )plexus 2-Submucosal (Meissner's) plexus

Located between longitudinal and circular muscle layers circular muscle layers & mucosa
For control of Motility Secretion & blood flow
• Contain sensory neurons, interneurons, motor neurons, Connected to CNS via autonomic fibers
• Can control all functions independently of extrinsic innervation
• Neurons secrete: serotonin, NO, VIP, acetylcholine, NE
2. Extrinsic Innervation: dual innervation from ANS
Parasympathetic cholinergic fibers Sympathetic noradrenergic
↑activity of smooth muscles ↓activity of smooth muscles
While causing sphincter contraction
1. Preganglionic fibers 1. Preganglionic fibers synapse in ganglia
A- Vagus nerve outside GIT
B- Pelvic nerve 2. Post ganglionic adrenergic fibers, secrete
2. Post ganglionic fibers are either norepinephrine on neurons of ENS or
A- Cholinergic neurons (Ach) Directly on smooth muscle
B- neurons secrete peptides as VIP On blood vessels,cause VC
Vagal nerve carry sensory information from blood vessels have also intrinsic innervation
GIT to CNS VIP + No in ENS →cause VD

Sensory information as fullness, ischemia, Reach CNS to,

o Initiates feedback control to digestive organs
o Cause sensations such as satiety
o Release mediators from their peripheral ends→ affecting motor and secretory function.

B- intrinsic endocrine

A- Endocrine hormones: Secreted from enteroendocrine cells or nerves in GIT→ Pass from portal to
systemic circulation and back to target cells in GIT
B- Paracrine Polypeptides: released from similar cells in GIT and exert their actions locally on target cells

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 Gastrin

Site of release G cells in antrum, duodenum, pancreas

Mechanism of secretion
A- Mechanical: Distension
B- Chemical: Protein digestive products as tryptophan & ↑pH
C- Nervous: vagal stimulation (release Gastrin Releasing peptide (GRP) not blocked by atropine
Stimuli inhibit gastrin secretion ↓pH (acid) by direct action on G cell or on D cells that stimulate
Somatostatin secretion that inhibit gastrin release = negative feeds back
Actions:
a) Stimulates gastric motility
b) Stimulate HCL secretion from parietal cells (HCL is essential for conversion of pepsinogen into pepsin)
c) Trophic Action: stimulates growth of mucosa
d) Stimulates insulin secretion
Zollinger-Ellison Syndrome: gastrinoma in pancreas→ hyper-gastrinemia →↑acid secretion→ ulcer
In pernicious anemia→ destruction of parietal cell →↑ gastrin secretion to high levels

Cholecystokinin-CCK
Site of release I cells in upper small intestine
Mechanism of secretion Presence of digestive products in small intestine
Actions
a) Stimulates pancreatic enzyme secretion
b) ↑action of secretin on pancreas
c) trophic effect on pancreas.
d) Contraction of wall of gall bladder & relaxation of sphincter of oddi
e) Inhibits gastric motility
f) contraction of pyloric sphincter to prevent reflux
g) ↑motility of small intestine and colon
h) On Brain: produces satiety → inhibits food intake

Secretin
Site of release S cells in upper small intestine
Mechanism of secretion ↓ duodenal pH < 4.5 & digestive products
Actions
a) Stimulates pancreatic & biliary HCO3 secretion → Neutralize pH in duodenum→ create suitable pH
suitable for action of pancreatic enzymes (-ve feedback)
b) ↑action of CCK
c) ↓ acid secretion by parietal cells

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 Glucose
d) dependent insulino-tropic peptide (GIP)
Site of release K-cells in upper small intestine
Mechanism of secretion Presence of glucose & fat in duodenum
Actions
a) Stimulate insulin secretion with GLP = (incretin hormones)= postprandial insulin response
b) stimulates production of B cells and inhibits their apoptosis.
Hyperplasia of K- cells & ↑ GIP levels are observed in obesity
INCRETIN HORMONES: released in response to nutrients in GIT and ↑insulin secretion
Vasoactive intestinal peptide (VIP)

Site of release in myenteric and submucosal neurons in GIT.

Mechanism of secretion released by many stimuli as acetylcholine, ATP, serotonin
Actions
a) VD & ↑ intestinal water and bicarbonate secretion
b) ↑ pancreatic & biliary water and bicarbonate secretion
c) Inhibits HCI secretion
d) Relaxation of smooth muscles & sphincters
VIP- secreting tumors ( VIPomas ) Cause severe watery diarrhea, hypokalemia and achlorhydria.
Irritable bowel syndrome (IBS): Stress `Induced diarrhea is mediated via stimulation of CRH and
VIPergic submucosal neurons.
• treated with VIP- receptor antagonists
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Motilin
Site of release: MO cells in stomach, small intestine, and colon
Mechanism of secretion: Motilin binds to receptors on enteric neurons in stomach, small intestine, colon
Actions
a) ↑ motility during fasting.
b) Regulates migrating motor complex ( MMC ) that move undigested food into colon
o level is reduced with ingestion or Pregnancy→ cause constipation
o
Somatostatin (paracrine manner)
Site of release D cells of GIT & pancreas.
Mechanism of secretion: Presence of digestive products &, ↓ duodenal pH
Actions inhibitory to GIT→ maintain continuous supply of nutrients
a) Inhibits gastrin & secretin, CCK, GIP
b) Inhibits acid secretion & Inhibit gastric motility
c) Inhibit endocrine & exocrine pancreatic secretion
d) Inhibit gall bladder contraction
e) Inhibit absorption

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 Mainly 3 pairs of Salivary glands Type of secretory cell (acini)
1. Parotid gland Serous 25 % of saliva
2. Sublingual gland Mixed (mucoserous) 5%
3. Submandibular gland Mixed (mucoserous) 70%
Small Buccal glands Mucous

Composition of saliva Volume: 1500 ml/day PH: 7 Contents: Electrolytes, Enzymes: Ptyalin,
Mechanism of salivary secretion 2 stages
First stage Second stage
Acini secrete 1ry secretion Ducts modify primary secretion
Ionic composition as • Na+ are actively reabsorbed in exchange with K+
plasma (ECF) • stimulated by aldosterone.
• Na+ reabsorption > K+ secretion →causes Cl- to be reabsorbed
• Bicarbonate is actively secreted.
• Duct: impermeable to water.
• Net:↓ Na, Cl in saliva ,↑K, HCO3 > plasma.
1ry secretion is Isotonic 2nd secretion is hypotonic

• During maximal salivation (parasympathetic stimulation):

o Na+, CI- and HCO3- in saliva as in plasma, K+ conc. not ↑, as ductal modification is markedly ↓by
rapid flow

Functions of Saliva

A- Protection of oral mucosa

1. Cooling hot foods.
2. Neutralizing acid → Maintain oral pH at 7.0.& relieve heartburn
3. Maintaining healthy oral mucosa: Washing away & attacks bacteria via Lysozyme & IgA
Lactoferrin is bacteriostatic.
B- Protection of teeth
1. Buffers in saliva maintain oral pH at 7.0. → saliva is super-saturated with calcium →
✓ Teeth do not lose calcium (as Ca++ precipitate in alkaline medium).
✓ Loss of Ca++ → cause dental caries.
2. Fluoride (added to drinking water) protects teeth enamel.
3. Proline-rich proteins protect teeth enamel
(xerostomia) →dry oral-mucosa →becomes ulcerated and infected, ↑incidence of dental caries
C- Digestion via Salivary -amylase (Ptyalin) →digests starch.
Acts in mouth, Inactivated by low pH of stomach , Reactivated by high pH of small intestine.

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D- Lubrication and Wetting
1. Swallowing: lubricates food via mucin
2. Speech: facilitates movements of lips and tongue
3. Taste: dissolve molecules → stimulate taste receptors.

Control of Salivary secretion:

• Salivary glands are continuously secreting, under ANS control , Inhibited by fear, or during sleep
Innervation of salivary glands
1. Parasympathetic efferent fibers
Center Superior salivary nucleus in medulla Inferior salivary nucleus in medulla

Efferent Chorda tympani branch of facial nerve→ Glossopharyngeal nerve

relay in submandibular ganglion. relay in otic ganglion.

1. Gland Sublingual and Submandibular salivary glands Parotid gland

Effect • Marked VD due to local release of VIP + acetylcholine

• Profuse secretion of watery saliva (High in electrolytes)

• Atropine →↓ salivary secretion

2. Sympathetic
• Center From LHCs of 1st & 2nd thoracic segments→
• Post ganglionic fibers cause → V.C. & secretion of small amount of saliva
Secretion of saliva can occur in response to
1. Unconditioned reflexes:
Stimulus: Taste, tactile, and thermal stimuli from mouth or reflexes from stomach and upper intestine
due to swallowing of irritating foods
Center: salivary nuclei
Response: ↑ salivary secretion.
2. Conditioned reflexes:
Stimulus Sight, smell, hearing preparation of food
Center taste and smell areas of cerebral cortex or Appetite area in hypothalamus → excites salivary nuclei

Stomach

• Contains many deep glands , open on a common chamber (gastric pit) that open on mucosal surface
• Stomach has a very rich blood and lymphatic supply.
• Parasympathetic: 2 vagi
• Sympathetic: from celiac plexus.

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Gastric secretion
Volume 2.5 liters/day
PH highly acidic= 1
Constituents Water, Electrolytes, Enzymes: pepsinogen, Mucus, Intrinsic factor for absorption of vit. B12

Functions of HCL
1. Activate pepsinogen → pepsin.
2. Provide optimum pH for action of pepsin.
3. Dissolves food →into chyme
4. Helps iron & calcium absorption
5. Sterility of stomach
6. Stimulates flow of bile.

Mechanism of acid secretion:

• HCL is secreted by parietal cell via active process
1. Cl- is actively transported to the lumen→ creates -ve potential → Leads to passive diffusion of K+
2. H2O dissociates into H+ and OH- in the cell.
3. H+ is actively secreted to lumen in exchange for K+ by H+/K+ ATPase pump (proton pump).
4. OH + CO2 (form metabolism or blood) carbonic anhydrase HCO3-
5. HCO3- diffuses out of the cell → to blood in exchange for Cl-
6. H2O diffuse to the lumen by osmosis.
Alkaline tide: as HCl is secreted by the parietal cells, HCO3- is added to gastric venous blood →↑PH

Stimuli of HCl secretion & their mechanism of action

Stimuli Receptor 2nd messenger
Histamine H2 receptors ↑intracellular cAMP
Acetylcholine M3 muscarinic receptors ↑intracellular Ca++.
Gastrin directly on oxyntic cells by ↑intracellular Ca++ or indirectly through stimulating
secretion of histamine from enterochromaffin-like cells (ECL cells).

• 2nd messengers → transfer H+/K+ ATPase to plasma membrane

II-Secretion and Activation of Pepsinogen

Secreted by chief (peptic) cells
✓ Activated by HCI at pH 2 to active pepsin
✓ Active pepsin →activates pepsinogen = positive feed-back.
✓ Pepsin is inactivated by alkalinity of duodenum
Action: digest protein into peptides (incomplete)

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III-Secretion of Intrinsic Factor from parietal cells with HCl.
Action: Essential for absorption of vitamin B12 in ileum
In Chronic gastritis → damage of parietal cells → causes achlorhydria & pernicious anemia.

IV-Secretion of mucus in the stomach

Soluble mucous Insoluble mucous
Secreted by mucus cells at r=the neck of Secreted by surface epithelium of body and fundus, as well
gastric glands as esophageal and pyloric junctions.
In response to vagal stimulation. Action: It forms gel layer 1.5mm in thickness→
Action: lubricates gastric chyme ✓ Protect gastric mucosa against mechanical friction
✓ Neutralize acid

Phases of Gastric Secretion

1. Cephalic stimulatory phase: (Nervous)→

Both conditioned reflex Signals from cortex or hypothalamus

and unconditioned reflexes (from mouth) → stimulate dorsal nucleus of vagus →↑ gastric
secretion by:
a. Acetylcholine → acts directly on gastric glands
b. GRP →↑ gastrin secretion.
• Accounts for 1/3 of gastric secretion

2. Gastric stimulatory phase: (Nervous and Hormonal)

• Presence of food in stomach →↑ gastric secretion by 3 mechanisms:

a. Long vago-vagal reflexes
b. Local enteric reflexes (submucous plexus):
c. Gastrin secretion.
• Accounts for 70% or 2/3 gastric secretion

3. Intestinal inhibitory phase: (Nervous and Hormonal): Presence of food in duodenum→↓ gastric
secretion by: Enterogastric reflex. & Hormones as GIP and secretin.
Mechanisms of inhibition of gastric secretion

1. Enterogastric reflex
2. Hormones as GIP, secretin
3. ↓pH< 2 in pyloric region & duodenum →↓gastrin
4. Emotional depression and fear, via impulses from cerebral cortex→ inhibit dorsal vagal nucleus.
5. Somatostatin (paracrine), inhibit both G and ECL cells as well as secretion by parietal cells

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 Mucosal Barrier
1. Insoluble mucus: secreted by surface mucus cells → forms flexible gel, coats the mucosa.
2. HCI secreted by parietal cells in finger like channels
3. Integrity of the membrane of mucosal cells:
o impermeable to H+
o Active transport →pumping H+ into lumen, and Na+ into ISF.
4. Prostaglandins →↑mucosal blood flow→ Stimulate mucus and bicarbonate secretion→ augment
gastric mucosal barrier & inhibit acid secretion

Causes of peptic ulcers

Breakdown of gastric mucosal barrier & gastric ↑secretion of HCl

irritation
• Ethanol, vinegar Zollinger-Ellison syndrome: see before
• Aspirin and non-steroidal inflammatory drugs,
corticosteroids → ↓production of
prostaglandins→↓ mucus and HCO3- secretion.
• Infection with Helicobacter pylori
As a result of breakdown of the barrier:
• H+ ions diffuse from lumen to the cell, Na+ ions diffuse from plasma to the cell.
→ destroy metabolic function→ forming ulcers

Treatment of peptic ulcers:

(1) Inhibit acid secretion:
a) Block H2 receptors e.g. by cimetidine.
b) Proton pump inhibitors e.g. Omeprazole.
(2) Surgical removal of tumors.
(3) Stop aspirin and non-steroidal anti-inflammatory drugs.
(4) Antibiotics for Helicobacter pylori

Pancreatic Secretion

Composition
Volume 1500 ml/ day.

pH alkaline (high HCO3-) with Bile & intestinal secretion → neutralize HCl→↑ pH of duodenum to 6.0- 7.0.

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 Contents

A- Enzymes: sufficient for complete digestion even in absence of salivary amylase & gastric pepsin

o Secreted by pancreatic acini as inactive proenzymes.

o In duodenum, trypsinogen is converted to active trypsin by brush border entero-peptidase (↑by CCK)
o Trypsin activates trypsinogen and chymotrypsinogens (autocatalytic reaction)
o Congenital Entero peptidase deficiency → causes protein malnutrition.

B- Secretion of Trypsin Inhibitor:

o The same cells secrete proteolytic enzymes secrete simultaneously trypsin inhibitor→ prevents
activation of trypsin inside secretory cells & acini & ducts
o In severe damage of pancreas or blockage of the duct
→ pancreatic secretions accumulate in damaged areas & rapidly activated & attack the pancreas
causes disruption of pancreatic tissue and necrosis of surrounding fat
→ Lethal acute pancreatitis due to shock, or lifetime pancreatic insufficiency.
o Marked ↑ in plasma amylase or lipase in acute pancreatitis

Mechanism of Secretion of Bicarbonate Ions via epithelial cells of the ducts

𝑐𝑎𝑟𝑏𝑜𝑛𝑖𝑐 𝑎𝑛ℎ𝑦𝑑𝑟𝑎𝑠𝑒
1. CO2 (from the blood) + H2O and→ H2CO3→ HCO3- + H+
2. H+ is exchanged for Na+ at basolateral border (2nd active transport).
3. HCO3- actively transported with Na+ ions (for electrical neutrality) at luminal border into lumen
4. Na+ and HCO3- into duct lumen creates osmotic pressure →cause osmosis of water (isosmotic solution)
Acid Tide: entry of H+ →↓ pH of pancreatic venous blood→ neutralizes alkaline tide of gastric venous blood
Regulation of Pancreatic Secretion
1- Nervous regulation During cephalic & gastric phases of gastric secretion →↑ vagal discharge → activate
pancreatic acini → secretion of small amount of pancreatic juice rich in enzymes.
2- Hormonal regulation (main mechanism)

Secretin Cholecystokinin (CCK):

Site of release: see before Site of release: see before

Stimulus: see before Stimulus: see before
Action: acts on pancreatic ducts (↑c-AMP) Action: acting on acinar cells (PLC → see before
See before
Aim:

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Liver Facts During pregnancy→↑ liver size due to ↑ metabolism
• Liver store 13% of the blood + store Vitamin A.
• Liver can regenerate itself. as 25% of healthy liver remains→ it can become whole again.
• Alcohol → toxic to liver
•
Functions of the liver

1. Vascular Functions store 400 ml. of blood. (replace lost blood).

2. Metabolic Functions:
A- CHO metabolism liver functions as "glucostat" → maintain constant glucose level
B- Fat metabolism oxidation (energy) & Formation of lipoproteins as VLDL, HDL.
C- Protein metabolism liver produce
i- Most plasma proteins (90%)as Albumin (major protein) → regulate blood volume
• Liver dysfunction→↓ albumin → edema
ii- Apo-Ferritin + proteins bind hormones
iii- Most coagulation factors
• Liver produces bile salts essential for absorption of fat-soluble vitamin.
• ↓clotting factors or not absorbed vit K → Uncontrolled bleeding.
iv- Synthesis of all non-essential amino acids.
v- Deamination of amino acids for energy or transformed into CHO
vi- Formation of urea for removing of ammonia
D- Storage of vitamins & minerals: as vitamin A, D and B12, & minerals as iron:
• Apoferritin-ferritin system of liver acts as blood iron buffer.
o When iron in body fluids is ↑ → iron combines with apoferritin to form ferritin.
3. Hormonal functions of your liver: Secretes
- IGF-1→ promotes growth. , Angiotensinogen → involved in ABP control
- Chemical conversion of thyroid hormone into its most active form.
- breaking down and removing many hormone (when not needed)
4. Role in digestion and absorption (exocrine gland)
o Formation of bile containing bile salts→ Digestion and absorption of fats , HCO3 neutralize acid
5. Liver and Immunity: liver is rich in cells of innate immune system as
o NK cells → produce INFγ & cytotoxic towards tumor cells.
o Kupffer cells: derived from monocytes → Secrete cytokines →activate immune systeminitiating
inflammation
• Depending on their type:
a) Periportal cells: more active in phagocytosis→ 1st line defense towards gut derived bacteria
b) Perivenous kupffer cells: smaller and produce NO, prostaglandins

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6. Anti-inflammatory function and the Acute Phase Response
- Detecting and responding to inflammatory signals from other sites.
- cytokines enter blood stream →detected by hepatocytes→↑ acute phase protein production
• Responsible for systemic effects of inflammation
• Inducing leukocytosis, pyrexia
• Massive immune cell infiltration to site of initial inflammation.
• limit excessive inflammation as
➢ inhibition of neutrophil function by protease inhibitors,
➢ inhibition of TNF production
7. Secretory and excretory functions:
- degrade old RBC's into breakdown products, as bilirubin → eliminated via urine and stool.
- In liver failure→ jaundice = yellow coloration of skin & eyes
8. Detoxification or excretion of drugs, all steroid hormones), drugs, , and waste
- In liver failure → ↑toxicity
9. Role of liver in controlling appetite:
- ↑glucose levels →↑ FGF21 secretion from liver→ to PVN in hypothalamus to ↓CHO intake→
↓sweet-seeking behavior and meal size.
- FGF21: involved in insulin sensitivity , modulation of hepatic fatty acid oxidation

Regulation of bile secretion

➢ ↑ by vagus nerves & secretin→↑ H2O and HCO3 of bile via its effect on bile ducts.
➢ Bile salts reabsorbed from intestine→ most important physiologic choleretics.
Choleretics: ↑secretion of bile
N.B.: when bile salt reabsorption is prevented by resection or by a disease of terminal ileum
→ interrupts enterohepatic circulation→ 50% of ingested fat appears in stools
1. Stools become bulky, pale, foul-smelling and greasy (steatorrhea)
2. Malabsorption of fat-soluble vitamins (A, D, E and K).
The Gallbladder
Functions of the Gallbladder
1- Storage of Bile:
2- Concentration of Bile: as Maximum volume of the gallbladder = 60 ml, but can store 500 ml by active
transport of Na→ passively draws Cl, HCO3, H2O→↑ concentrations

3- Prevention of marked rise in Intra-biliary pressure: as ↑ pressure → stop bile secretion

4- Acidification of Bile: due to HCO3 absorption →keeps lecithin, cholesterol, bilirubin, in solution

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Control of Emptying of the Gallbladder=Cholagogues= cause contraction of gallbladder
1) Cholecystokinin (CCK): major stimulus for gallbladder contraction & sphincter of Oddi relaxation.

2) Vagal stimulation: less strong gallbladder contraction and sphincter of Oddi relaxation.

Gallstones: Cholelithiasis (gallstones)

1. Cholesterol Stones in USA, Europe (85%)

• Cholesterol: insoluble in water→ kept in solution in bile via formation of micelles in presence of bile salts

• When proportion of cholesterol and bile salts is altered→ cholesterol form stone

• Radiolucent

2. Calcium Bilirubinate Stones

• Infection of biliary tree → bacterial deconjugation of conjugated bilirubin.

• Free bilirubin combines with calcium → calcium bilirubinate (insoluble)→ form stone

• radiopaque stones
Effect of Cholecystectomy bile empties slowly but continuously into intestine, → insufficient
digestion of fat Avoid High-fat meals

Secretions of the Small Intestine

1. Intestinal Mucus: Covers and, lubricates, protect as it Binds bacteria & immunoglobulins
o Mucus is secreted by Surface epithelial cells , Goblet cells
a) Brunner's glands in duodenum→ secrete mucus in response to:
1. Chemical and physical irritation of mucosa.
2. Cholinergic stimulation & Inhibited by sympathetic→ peptic ulcers in 50% of all cases
3. GIT hormones, especially secretin.
2. Secretion of Intestinal isotonic Alkaline fluid: NaCl & HCO3, 1800 ml/day , Slightly alkaline (7.5 - 8.0).
• Formed by epithelial cells in crypts of Lieberkühn
Rapidly absorbed by villi → watery vehicle for absorption of substances from chyme
3. Enzymes: Peptidases, disaccharidases, lipase at brush border of epithelial cells (not secreted)

Regulation of Small Intestinal Secretion

1. Local Nervous Reflexes Most important, especially reflexes initiated by physical or chemical irritation

2. Hormonal Regulation:

a- Secretin and cholecystokinin →↑ secretion.

b- VIP (secreted by GIT nerves), ↑intestinal secretion of electrolytes & water.
N.B.: VIP-secreting tumors in patients with severe diarrhea.

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Types of Movements in the Gastrointestinal Tract
• intrinsic property, or reflexed from ENS or CNS or paracrine & endocrine GIT hormones

A. Propulsive movements =Peristalsis:

Definition: property of syncytial smooth muscle tubes
Stimulation at any point in the gut →cause contractile ring spreads along the gut.
Stimulus:
1. Mechanical: distention
2. Chemical or physical irritation
3. Nervous: parasympathetic signal
Mechanism: distention→ activates Sensory neuron→ releases serotonin → activate

Cholinergic neurons in retrograde direction cholinergic neurons in an anterograde direction

release substance P and acetylcholine→ causing release NO and (VIP), → causing relaxation ahead
contraction behind the stimulus of the stimulus
Control: Myenteric Plexus
• Prove: no or weak Peristalsis in absence of myenteric plexus or if blocked by atropine
Importance: move food forward

B. The Mixing Movements:

Description: Mixing movements modified in different parts
1- Peristaltic contractions → cause mixing when forward progression of contents is blocked by sphincter
2- Segmentation contractions: local intermittent contractions/every few centimeters, last 5 to 30
seconds; then new contractions occur at other points
Stimulus Distention
Control: by
• Slow waves →setting the rhythm of contraction & Enteric nervous system
Importance: mix food with secretion

C-Migrating Motor Complex (MMC)

Stimulus: fasting
Response: Repeated peristaltic wave travel a short distance and then die out.
o Then new wave starts lower than previous one.
o Slowly migrate → taking 2 hours to reach the large intestine.
Control initiated by motilin, stopped by food ingestion
importance: Moves undigested substances to large intestine
Prevents bacteria from remaining in the small intestine

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 Mastication (Chewing)

Control: Center: in the brain stem→ motor branch of 5th cranial nerve
Chewing reflex (stretch reflex):
• Bolus of food → cause descend of lower jaw →initiate stretch reflex of the muscles of
mastication →contraction→ raises the jaw → compresses bolus again.
• Importance of chewing:
- Breaks large food particles
- Stimulates taste & smell receptors →satiety.
- Stimulates salivary secretion →helps swallowing.
- Helps in satiety sensation

Swallowing (Deglutition)

A. Voluntary oral Stage of Swallowing:

• Pressure of the tongue upward and backward against the hard palate→ food is rolled
posteriorly into pharynx, Helped by contraction of mylohyoid muscle

B. Involuntary Pharyngeal Stage of Swallowing = reflex act

Movement of food through pharynx into esophagus 1-2 seconds
Stimulus: bolus of food
Receptor: around pharyngeal opening, especially on tonsillar pillars
Center : swallowing center in medulla and lower pons
Response:
✓ Rapid peristaltic wave in superior → then middle → then inferior pharyngeal muscles
✓ Upper pharyngoesophageal sphincter relaxes
Result: movement of food through pharynx into esophagus
Protection of air passages during swallowing:
1. Closure of posterior nares via elevation of soft palate
2. Closure of glottis (approximation of vocal cords).
3. Elevation of larynx to be covered by epiglottis
4. Inhibition of respiration (swallowing apnea) for 1-2 sec.

C. Involuntary Esophageal Stage of Swallowing Movement of food from pharynx to stomach

2 peristaltic movements:

1. Primary peristaltic wave: continuation of peristaltic wave begins in pharynx, passes all
the way from pharynx to stomach in 8 to 10 seconds.

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 2. Secondary peristaltic waves: result from distention of the esophagus by retained food
if primary peristaltic wave fails

Function of Lower Esophageal Sphincter (Gastro-esophageal Sphincter) (LES):

• Sphincter tonically contracted, in contrast to the mid and upper esophagus

• Function prevents reflux of contents into esophagus
• When peristaltic wave passes down the esophagus→ "receptive relaxation" relaxes
LES a head of peristaltic wave → easy propulsion of swallowed food
Tone of LES is under neural control and other factors:
a. Acetylcholine: released from vagal nerve endings →contractions of LES.
b. NO & VIP from interneurons innervated by other vagal fibers → relax LES
c. High level of progesterone during pregnancy →↓Tone of LES → reflux and heartburn.
d. Diet (high sugar & fat) → cause heartburn
Abnormalities of the tone of LES:
1- Gastroesophageal reflux: ↓ tone of LES → reflux of acid into esophagus → cause heartburn and
esophagitis →ulceration and stricture of esophagus (scarring)
2- Achalasia: incomplete relaxation of LES →accumulation of food → massive dilation of esophagus
• Cause: deficient myenteric plexus → deficient release of NO and VIP.
• Treatment:
• dilation of the sphincter,
• esophageal muscle incision or
• injection of botulinum toxin in the LES to inhibit acetylcholine release.

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Gastric motility

A. Storage Function of the Stomach (Receptive relaxation)

Function of proximal motor unit (fundus & body).
• Volume of empty stomach: 50 ml
• Pressure in the proximal motor unit = intra-abdominal pressure
• Stimulus: gastric distension
• Control (Regulation):
1) Vago-vagal reflex (abolished by vagotomy)
2) Relaxation triggered by peristaltic wave in esophagus
• Response: reflex relaxation of stomach
• Aim: ↑ capacity for food (can accommodate 1-1.5 liters).

B. Mixing and Propulsion of Food in the Stomach:

• Control: Initiated by Gastric Slow Waves ((BER)
❖ Start at midpoint of the greater curvature (pace maker of the stomach)
❖ Rate = 3-5 cycles/min
❖ Some lead to spike followed by peristaltic wave at rate 3 / minute at rest
❖ ↑with vagal stimulation or gastrin hormone to 5 / min. (never exceed BER)
• Response: contractions: begin in the middle of the body → ↑in force & velocity towards pylorus
• Contraction of antrum→ followed by contraction of the pyloric region & duodenum
✓ Prevents solid masses from entering the duodenum
✓ Contraction of pyloric segment persist longer after relaxation of duodenum due to
stimulating action of (CCK) on pyloric sphincter to prevent regurgitation

Regulation of Gastric Evacuation

1. Gastric factors: Distension of the stomach →↑ emptying via

• Nervous reflexes: long vago-vagal reflexes, short local reflexes Hormonal: gastrin
2. Intestinal factors:
a. Nervous: (Enterogastric Reflex): ↑acidity, Fat, protein, distension→ inhibits gastric emptying
b. Hormonal: presence of fat in duodenum →releases (CCK, GIP and secretin) →
Inhibit emptying, with closure of pyloric sphincter.
c. Consistency of food: Liquid food is evacuated more rapidly than solids
CHO evacuated rapidly > protein > fat (slowest)
d. Reflexes from outside GIT:
• Pain → reflex inhibition of gastric motility.
• Emotions →↑or ↓ gastric motility.

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 N.B.: Hunger contractions (Hunger pains):
• Painful contractions associated with fasting.
• Feeding center in hypothalamus is normally active, unless inhibited from satiety center.
• Hypoglycemia →↑ activity of feeding center → that sends impulses to:
- Limbic cortex →hunger sensation.
- Vagal nucleus in medulla→ hunger contractions & pain

Vomiting
Definition reflex abnormal emptying of gastric contents through esophagus and mouth
reverse peristalsis empties material from upper part of small intestine into the stomach
• Vomiting center: in medulla, anatomically associated with respiratory center
• importance: protective mechanism: protect GIT against toxic or irritant substances

Causes
Reflex:
a. Mechanical stimulation of the posterior part of the tongue.
b. Irritation of the gastric mucosa
c. Irritation or obstruction of the intestine
Central: stimulate vomiting center in the medulla directly:
A- Drugs: apomorphine.
B- Hypoxia and acidosis.
C- Motion sickness, due to labyrinthine stimulation.

Mechanism of vomiting preceded by nausea, sweating, salivation and tachycardia, then:

1. Stomach wall is completely passive:
- Relaxation of the wall of the stomach.
- Relaxation of LES.
- Contraction of pyloric sphincter
2. Deep inspiration (strong contraction of the diaphragm) + contraction of abdominal muscles →↑
intra-abdominal pressure →squeeze gastric contents up through a relaxed LES
3. Protection of air passages as during swallowing:
a. Elevation of soft palate to close the nasal cavity.
b. Closure of the glottis
c. Apnea.

Complications: Loss of water and HCL→ dehydration and metabolic alkalosis

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Movements of the Small Intestine

A- Segmentation (Mixing) Contractions

Stimulus Distention
Control by slow waves & ENS
Prove: become weak when excitatory activity of ENS is blocked by atropine.
Rate Maximum frequency in duodenum =12 /min / in terminal ileum=9 /min
Response localized contractions spaced at regular intervals
As one set of contraction relaxes,
A new set begins in between the previous ones
Aim mixing food with secretions.

B- Peristalsis in Small Intestine

Stimulus: distention of the stomach/ duodenum
Control
• Nervous regulation (gastroenteric reflex) →conducted via myenteric plexus from stomach to
small intestine.
• Hormonal regulation: gastrin, CCK, motilin, →↑ intestinal motility.
secretin and glucagon →inhibit small intestinal motility.
Rate Faster in proximal intestine and slower in terminal intestine
→ move chyme 1 cm/min→ 3-5 hours for passage of chyme from pylorus to ileocecal valve.
Response contractile ring spreads along the gut
Aim move chyme forward & expose it to mucosa.

C- Migrating Motor Complex (MMC): see before

Gastroenteric (gastroileal) Reflex:
• Caused by distention of the stomach
• Conducted via myenteric plexus from the stomach to small intestine→ ↑ peristaltic activity
Peristaltic Rush: rapid peristaltic activity Caused by Irritation of intestinal mucosa (infectious diarrhea)
Dynamic (Paralytic) Ileus: Diffuse ↓in peristaltic activity
Cause: due to activation of opioid receptors as a complication of abdominal operations
→ trauma to small intestine or peritoneal irritation
→ ↑discharge of noradrenergic fibers in splanchnic nerves
→ cause inhibition of intestinal motility

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THE COLON; LARGE INTESTINE

Function: absorption of water, Na+ and other minerals.

• Absorbs 90% of fluid present in 1- 2 L chyme → turning it to 200 –ml of feces.

Motility of the Colon (Types of Movements)

1. Segmentation contractions: similar to those in small intestine
• Mix the contents and exposing it to mucosa, facilitate absorption.
2. Peristaltic waves: propel contents toward the rectum.
• Unlike small intestine, ↑along colon→ lower at ileocecal valve and higher at sigmoid
3. Mass movement:
• Modified peristalsis, few times each day, often following breakfast.
• Simultaneous contraction of smooth muscle over large areas of the colon→ move feces
down into rectum → causes rectal distention → initiates defecation reflex.

Defecation: spinal parasympathetic reflex

Stimulus: rectal distention………………mass movement move
Receptors: nerve endings in the rectum
Afferent: pelvic nerve
Center: sacral segments of spinal cord
Efferent: pelvic nerves
Response: contraction of smooth muscles of distal colon and rectum
relaxation of internal anal sphincter.
❖ Modification:

If the conditions are not socially acceptable If the conditions are acceptable

Cerebral cortex causes Cerebral cortex send signals to cause

voluntary contraction of external anal Voluntary relaxation of External anal sphincter
sphincter & inhibits defecation reflex Contraction of abdominal muscles + deep breath
→↑intra-abdominal pressure

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