Download Burns GI Physiology 2017

OPTO 5331 General Pathology and Medicine
GI Physiology 2017
Dr. Alan Burns
Rm 2168
[email protected]
Overview
1. GENERAL ORGANIZATION - Components, Blood Supply, Control and
Coordination
2. NEURAL AND CHEMICAL CONTROL - General Organization,
Neural Control, Chemical Control, Reflex Control of Motility
3. MOTILITY-General Principles, Chewing and Swallowing, Esophagus,
Stomach, Small Intestine,Vomitting, Large Intestine or Colon
4. SECRETION - General Principles, Secretion (Salivary, Gastric,
Pancreatic,Bile)
5. DIGESTION & ABSORPTION – General Organization, Carbs,
Protein, Lipid, Vitamins, Ions and Water
6. OBESITY
1.1 Components
Chewing, Hydrolysis
– make bolus and swallow
Propel bolus
Churning,
Hydrolysis,
Storage - chyme
(gastric juice and
partly digested food)
Absorption
Hydrolysis,
Absorption
Storage
Expulsion
1.2 Blood Supply
• GI tract is supplied by splanchnic circulation which also
supplies pancreas, spleen and liver
• Portal system delivers all GI tract venous blood to the liver
• In the liver, blood passes through a second capillary bed
where the RES removes bacteria before blood re-enters
general circulation
1.3 Control and Coordination
• GI motility and secretion is controlled through a complex of sensors
and effectors so that digestion and absorption are optimized
• GI motility must also be coordinated with secretion from pancreas
and gall bladder
• Receptors outside and inside the GI tract receive visual, mechanical
and chemical stimuli
• Receptor activation induces responses through changes in autonomic
and enteric nervous systems and through the effect of GI hormones
• Understanding GI function requires an understanding of many
interrelated reflex loops
Overview
1. GENERAL ORGANIZATION - Components, Blood Supply, Control and
Coordination
2. NEURAL AND CHEMICAL CONTROL - General Organization,
Neural Control, Chemical Control, Reflex Control of Motility
3. MOTILITY-General Principles, Chewing and Swallowing, Esophagus,
Stomach, Small Intestine,Vomitting, Large Intestine or Colon
4. SECRETION - General Principles, Secretion (Salivary, Gastric,
Pancreatic,Bile)
5. DIGESTION & ABSORPTION – General Organization, Carbs,
Protein, Lipid, Vitamins, Ions and Water
6. OBESITY
2.1 General Organization
• GI tract motor activity is largely performed by SMCs
• Wall of GI tract is multilayered (glands, nerves and muscles)
• GI tract has its own nervous system (enteric)
• GI tract musculature is primarily smooth muscle. Only upper
1/2 of esophagus and external anal sphincter are skeletal
GI Tract Wall
Covered by mesothelium
• Mucosa
(mucous membrane)
• Submucosa
• Muscularis externa
(Peristalsis)
Auerbach’s
Plexus
• Serosa (adventitia)
Meissner’s
Plexus
(Secretion)
2.2 Neural Control
• Extrinsic component
Parasympathetic nervous system
Sympathetic nervous system
• Intrinsic component
Enteric nervous system
2.2 Neural Regulation
sympathetic
parasympathetic
Motility
Motility
Secretions
Secretions
Sphincter
constriction
Sphincter
constriction
Gastrin
2.2 Neural Regulation
Enteric Plexuses
•
•
•
Plexuses are
networks of nerve
fibers and ganglion
cell bodies
Interneurons
connect afferent
sensory fibers with
efferent neurons
to smooth muscle
and secretory cells
Local and central
reflex pathways
(NEXT SLIDE)
2.2 Neural Regulation
Enteric plexuses interconnected
by fiber tracts
Reflex Control of Motility
• Reflexes exist within gut to regulate motility
• Mechanical and chemical stimuli initiate reflexes
• Reflexes are classified by neural systems involved:
a. Enteric
b. Prevertebral ganglia with sympathetic afferents
and efferents
c. Spinal cord and brain stem with vagal afferents
and efferents
d. Combination of a, b and c
2.3 Chemical Control - Peptides
• GI peptides divided into 3 classes: hormones, paracrines and
neurocrines
• Hormones – released by cells distant from their site of action
and carried to target cells by the blood (gastrin,
cholecystokinin (CKK), secretin, gastrin inhibitory peptide
(GIP) and motilin)
• Paracrines – released by cells adjacent to target cell and
reach target by diffusion (somatostatin and histamine)
• Neurocrines – similar to paracrines but released solely by
nerves (vasoactive intestinal peptide (VIP), gastrin-releasing
peptide and enkephalins)
Summary of Chemical Control in GI Tract
Chemical Control – Hormones - FEEDBACK
• Gastrin
o chyme acidity triggers stomach G cells to secrete Gastrin
o Also, Gastrin-releasing peptide (GRP; vagus) stimulates
Gastrin release
o Gastrin increases stomach motility and chyme delivery to
duodenum
o pH (<3) inhibits Gastrin secretion (negative feedback)
• Cholecystokinin (CCK)
o chyme fat triggers duodenal I cell CCK secretion
o CCK stimulates pancreas to release lipase
o CCK also causes gall bladder to release bile into the cystic
duct for delivery to the duodenum
o CCK slows chyme secretion to give time for digestion
Chemical Control – Hormones -FEEDBACK
• Secretin
o acidic chyme triggers duodenal S cell secretion of Secretin
o Secretin stimulates pancreatic ductule cells to release
water and bicarbonate which neutralizes chyme
o Secretin inhibits Gastrin secretion
• Gastric Inhibitory Peptide (GIP)
o Fat, CHO and AA trigger duodenal K cell GIP secretion
o GIP inhibits acid and pepsin secretion and motility
• Motilin
o fat and acid trigger endocrine M cell Motilin secretion in
the crypts of duodenum and jejenum
o Motilin increases gut motility and pepsin secretion
Overview
1. GENERAL ORGANIZATION - Components, Blood Supply, Control and
Coordination
2. NEURAL AND CHEMICAL CONTROL - General Organization,
Neural Control, Chemical Control, Reflex Control of Motility
3. MOTILITY- General Principles, Chewing and Swallowing, Esophagus,
Stomach, Small Intestine,Vomitting, Large Intestine or Colon
4. SECRETION - General Principles, Secretion (Salivary, Gastric,
Pancreatic,Bile)
5. DIGESTION & ABSORPTION – General Organization, Carbs,
Protein, Lipid, Vitamins, Ions and Water
6. OBESITY
3.1 General Principles
Interdigestive period
- Every 90 min, migrating motor complex (MMC) a
strong contraction sweeps through the stomach and intestine
- MMC extends to ileum and is triggered by cyclical release
of “Motilin” from small intestine; inhibited by food
Digestive period
- During digestion, the basic electrical rhythm (BER) of
SMCs is altered by nerve and chemical control
Basic Electrical Rhythm (BER)
• Interstitial cells of Cajal (pacemakers) in stomach, small and
large intestine undergo spontaneous, rhythmic membrane
depolarizations which create a slow wave (BER)
• Slow waves are transmitted to smooth muscle cells
• Neuronal and hormonal factors do not modify the BER but they
do alter the SMCs likelihood of generating multiple APs in
response to slow waves
P=Perstalsis; S=storage; M=Mixing
3.2 Chewing and Swallowing
Chewing (mastication)
• Mechanoreceptors detect food and send signals to
swallowing center in brain stem which sends rhythmic
stimulatory signals to pharyngeal striated muscles
• Functions
Breaks food into small pieces
Mixes food with saliva
- mucins lubricate
- digestion begins (amylase and lipase)
Muscles of the Tongue
• Intrinsic muscles (longitudinal, transverse and
vertical) change tongue shape and size
• Extrinsic muscles attach to bone and change tongue
movement
3.2 Chewing
and Swallowing
Swallowing (deglutition)
•Three phases:
Oral (buccal) - voluntary
Pharyngeal - involuntary
Esophageal – involuntary
propulsion
(peristalsis)
3.3 Esophagus
Muscle: Upper 1/3 skeletal,
Middle 1/3 skeletal + smooth,
Lower 1/3 smooth
Upper esophageal sphincter
(skeletal muscle – voluntary control)
Lower esophageal sphincter
(smooth muscle – involuntary
control) and the crural
diaphragm constitute the
intrinsic and extrinsic sphincter,
respectively.
3.4 Stomach
Two regions with different motility
- “Orad” (fundus and proximal body)
- “Caudad” (distal body and antrum)
Functions
1) Orad, thin walled, relaxes and
receives food bolus from esophagus
2) Caudad, thick walled, churns food
bolus to fragment food and mix it
with chyme before propelling it into
duodenum
3.4 Stomach
3.4 Stomach
Gastric Emptying
• Approx 3hrs
• Regulated by duodenal contents
• Regulation achieved by hormones
• Migrating myoelectric complex
3.5 Small Intestine
Duodenum – receives
chyme; most digestion
(breakdown) occurs here
Jejenum – most
absorption of nutrients
occurs here
Ileum – Vit B12, A, D, E
and K; important
absorption
3.5 Small Intestine
• Functions :
Mixing chyme with digestive enzymes
Bringing digested material in to contact with mucosa
Propelling unabsorbed material in to large intestine
• Slow waves (BER)
• Two types of contraction:
- Segmentation - circular muscle
- Peristaltic - longitudinal muscle
• Muscularis mucosa – thin innermost layer of intestinal muscle
- contraction throws mucosa into folds
• Migrating myoelectric complex - extends to Ileum
3.5 Small Intestine
longitudinal SMC
circular SMC
3.6 Vomitting
• A reflex contraction of stomach and small intestine to rid the
body of noxious or toxic substances
•
Can also occur in response to other stimuli (dizziness,tickling
in back of throat, or painful injury)
•
Controlled by vomitting center in Brain medulla
•
Involves skeletal (abdominal wall, diaphragm) and smooth
muscle (esophagus, stomach and intestine)
•
Begins with contraction of stomach and small intestine
(reverse peristalsis) combined with skeletal muscle
to propel food out of the mouth
3.7 Large Intestine
• Receives 500-1500ml chyme/day
• Ileocecal sphincter relaxes intermittently to allow
entry
3.7 Large Intestine
•
Enteric nervous system regulates
two basic motility patterns:
segmentation and mass movement
•
Segmentation mixes and makes
intestine appear divided into small
interconnected sacs (haustra)
•
Mass movement pushes contents
significant distance
3.7 Large Intestine
haustra
• 1-3 times/day coordinated peristaltic
contraction occurs (mass movement)
propelling contents of one large
intestine segment into the next
downstream segment
• Segmentation stops in the area of the
large intestine undergoing mass
movement and the haustra disappear
and the contour of the colon is
smoothened
smoothened
3.7 Large Intestine
•
Defecation: Mass movement propels material from sigmoid
colon in to rectum
•
Rectal distension initiates involuntary relaxation of internal anal
sphincter (defecation reflex) as well as rectal peristalsis
• Defecation reflex involves enteric nervous system and parasymp.
• Rectal contraction signals urge to defecate.
• If convenient, external anal sphincter (skeletal muscle) relaxes (voluntary)
• If inconvenient, relaxation is not initiated, rectum accommodates and
reduces intensity of defecation reflex, and internal anal sphincter contracts
Overview
1. GENERAL ORGANIZATION - Components, Blood Supply, Control and
Coordination
2. NEURAL AND CHEMICAL CONTROL - General Organization,
Neural Control, Chemical Control, Reflex Control of Motility
3. MOTILITY-General Principles, Chewing and Swallowing, Esophagus,
Stomach, Small Intestine,Vomitting, Large Intestine or Colon
4. SECRETION - General Principles, Secretion (Salivary, Gastric,
Pancreatic,Bile)
5. DIGESTION & ABSORPTION – General Organization, Carbs,
Protein, Lipid, Vitamins, Ions and Water
6. OBESITY
4.1 General Principles
• GI secretions function to lubricate, protect, sterilize, neutralize and digest
• Secretions - specialized cells lining GI tract, pancreas, liver and gall bladder
• Secretions – generated by cell clusters connected to the GI tract lumen
• Secretion rate regulated by autonomic nerves and hormones
4.2 Secretion- Salivary
3 paired Salivary glands (acinar and ductal cells)
- Parotid glands (serous...alpha-amylase)
- Submandibular and Sublingual glands (mixed serous & mucous)
- amylase remains active until caudad stomach
Von Ebner’s gland
- Lingual lipase converts triglycerides to FFAs
- Lipase remains active until duodenum
Salivary Glands
• 1L of saliva/day
• Functions
Digestion (amylase, lipase)
Dilution and buffering
Lubrication (mucus)
• Composition : Water
Electrolytes
α-amylase
lingual lipase
mucins
Salivary Glands
(Acinus)
• Formation
Tonicity
pH
Step 1 acinar cells produce primary secretion
Step 2 ductal cells modify electrolyte composition
• Neural stimulation by parasympathetic (+++) and
sympathetic (+)
Salivary Glands
• Acetylcholine and norepinephrine released from parasymp and
symp post-ganglionic nerves, respectively, increase:
1)
2)
3)
4)
Ion transport activity
Blood flow
Cell metabolism
Myoepithelial cell (surround acinii) contraction
•
•
Chewing, taste and smell increase nerve activity and secretion
Sleep, fear and fatigue decrease nerve activity and secretion
4.2 Secretion - Gastric
• Major components :
Hydrochloric acid (HCl)
Pepsinogen (pepsin)
Intrinsic Factor*
Mucus
• Gastric glands (oxyntic and
pyloric)
• In oxynitic gland, parietal
and chief cells secrete into
a common gland
• Surface epithelial cells
*necessary for Vit B12 uptake in the ileum
4.2 Secretion - Gastric
• Distinct regions of the stomach produce 4 secretions
• Proximal (80%) of stomach (oxynitic gland area)
• Remaining (20%) of stomach (pyloric gland area)
pyloric
Histamine
ECL
cells
Somatostatin
Somatostatin (to circulation)
D
D cells
cells
Gastric Juice
• Regulation of Pepsin Secretion:
- Secreted in response to vagal nerve stimulation
- Acid is not only necessary for pepsin formation
but also for enhancing its secretion
Gastric Juice
HCl secretion
• Required to convert pepsinogen to pepsin
• Regulation:
- Acetylcholine (parasymp), histamine and
gastrin stimulate acid (HCl) secretion
- Somatostatin inhibits acid secretion
• Mechanism
• Phases : Cephalic
Gastric
Intestinal
Gastric Juice
• Acetylcholine released by
enteric parasymp. neurons
• Histamine (paracrine)
released from ECL
(enterochromaffin-like) cells
• Gastrin (hormone) released by
G cells in gastric epithelium
• Somatostatin
(paracrine/hormone) is
secreted by endocrine D cells
of the gastric epithelium
Gastric Juice
HCl secretion
• Required to convert pepsinogen to pepsin
• Regulation:
- Acetylcholine, histamine and gastrin
stimulate acid (HCl) secretion
- Somatostatin inhibits acid secretion
• Mechanism
• Phases : Cephalic
Gastric
Intestinal
Gastric Juice
- Mechanism of HCl secretion
*During a meal, the
elevated acid secretion
increases bicarbonate
levels in venous blood
leaving the stomach
(alkaline tide)
Gastric Juice
Termination of HCl secretion
• Gastric pH too low
• Acidic chyme in duodenum
• Fat digestion products
Gastric Juice
HCl secretion
• Required to convert pepsinogen to pepsin
• Regulation:
- Acetylcholine, histamine and gastrin
stimulate acid (HCl) secretion
- Somatostatin inhibits acid secretion
• Mechanism
• Phases : Cephalic
Gastric
Intestinal
Phases
Gastric Juice
o Cephalic
- stomach responds to sight,smell,taste or
thought of food
- 30% of total acid secretion occurs before
food enters stomach
o Gastric
– begins when food enters stomach
- increases gastric juice and gastrin
o Intestinal
– when chyme moves into duodenum
- triggers nerve impulses and hormones to
inhibit gastric secretion
Small Intestine
4.2 Secretion- Pancreatic
• Secretes pancreatic juice into duodenum
• HCO3- neutralizes acid… allows enzymes to function
• Formation :
ductal cells secrete aqueous HCO3- fluid
acinar cells secrete enzyme rich acinar fluid
• Regulation - neural and hormonal: regulates rate of
secretion not rate of synthesis
4.2 Secretion- Pancreatic
Phases: cephalic, gastric, intestinal (major stimulus – 70%)
• Cephalic and gastric (stomach distension) phases
stimulate enzyme secretion via Ach (vagal nerves)
• Intestinal phase initiated by duodenal contents
(acid, protein and fat)
4.2 Secretion- Pancreatic
Pancreatic enzymes and targets:
o Amylase - carbohydrates
o Lipase, cholesterol esterase, phopholipase - fats
o Trypsinogen, chymotrypsinogen,proelastase,
procarboxypolypeptidase, proaminopeptidase – proteins*
o Ribonuclease and deoxyribonuclease – nucleic acids
* Proteolytic enzymes activated in small intestine lumen
Pancreas
4.2 Secretion- Bile
• Liver secretes bile, for lipid digestion and absorption
• Gall bladder stores and concentrates bile
• Composition of bile
Bile
Bile Acids
Composition
Bile acids (50%)
Bile pigments (2%)
Cholesterol (4%)
Phospholipids (40%)
Electrolytes
Water
Cholic acid
1o
Chenodeoxycholic acid
Deoxycholic acid
2o (bacterial
Lithocholic acid
conversion of 1o)
Small intestine: bile emulsifies fats, forms micelles for excretion
Bile
• Ejection begins 30min
after ingestion
• Most release during
intestinal phase
• 80% recycled to liver
(enterohepatic circulation)
• 20% excreted
• Bile synthesis is
negatively regulated by
portal venous blood bile levels
Bile
Composition
Bile acids (50%)
Bile pigments (2%)
- primarily bilirubin
Cholesterol (4%)
Phospholipids (40%)
Electrolytes
Water
Bile
Composition
Bile acids (50%)
Bile pigments (2%)
- primarily bilirubin
Cholesterol (4%)
Phospholipids (40%)
Electrolytes
Water
Overview
1. GENERAL ORGANIZATION - Components, Blood Supply, Control and
Coordination
2. NEURAL AND CHEMICAL CONTROL - General Organization,
Neural Control, Chemical Control, Reflex Control of Motility
3. MOTILITY-Chewing and Swallowing, Esophagus, Stomach, Small
Intestine,Vomitting, Large Intestine or Colon
4. SECRETION - General Principles, Secretion (Salivary, Gastric,
Pancreatic,Bile)
5. DIGESTION & ABSORPTION – General Organization, Carbs,
Protein, Lipid, Vitamins, Ions and Water
6. OBESITY
5.1 General Organization
• Small intestine is primary site for
digestion and absorption
• Surface area increased by villi
and microvilli (brush border) –
surface are > basketball court
• Secreted and surface-bound
enzymes break down of food
5.1 General Organization
• Small intestine is extremely efficient
• 60% can be removed with no change in
carbohydrate or protein absorption
• Only if the Ileum is removed will
Vit B12 and fat absorption be impaired
• Absorption occurs by diffusion,
facilitated diffusion, active
transport, endocytosis and
paracellular transport
5.2 Carbs
• Ingested carbs (starch) converted to glucose,
galactose or fructose
• Only monosaccharides absorbed
Carbohydrates
Starch
Amylase
Trehalose
Lactose
Sucrose
α-dextrins
Maltose
Maltotriose
Trehalase
Lactase
Sucrase
Dextrinase
Maltase
Sucrase
Glucose
Glucose + Glucose
Glucose + Galactose
Glucose + Fructose
Carbohydrates
SGLT1: energy-dependent sodium-hexose cotransporter
GLUT5 and GLUT2 : facilitative hexose transporters
5.3 Protein
• Must be broken down to amino acid, di- or tri-peptides
• Digestion : Pepsin in the stomach
Pancreatic enzymes (see below)
Brush border enzymes
- (enterokinase, peptidases)
Inactive
Acted upon
by Trypsin
Trypsinogen
Chymotrypsinogen
Proelastase
Procarboxypeptidase A
Procarboxypeptidase B
Active
Trypsin
Chymotrypsin
Elastase
Carboxypeptidase A
Carboxypeptidase B
5.4 Lipids
• Triglycerides, cholesterol, phospholipids
• Digestion
Lingual and gastric lipase
Pancreatic lipases
Bile
Enzyme
Substrate
Products
Pancreatic lipase
Triglyceride
2 fatty acids + monoglyceride
Cholesterol ester hydrolase Cholesterol esters Cholesterol + fatty acid
Phospholipase A2
Phospholipids
Fatty acid + lysolecithin
5.4 Lipids
Enterocytes re-synthesize Chol E, TG and PL which are then
packaged into chylomicra or VLDL particles which are exocytosed
through lymphatics because they are too large to cross blood
capillary endothelium – entering blood via thoracic duct
5.5 Ions & Vitamins
• Iron
• Calcium
• Vitamins
- Fat soluble (A,D,E and K): incorporated into
micelles, diffuse into cells and then into chylomicra
- Water soluble (B, C, thiamine, niacin and folate):
carrier mediated uptake coupled to Na+ movement
Iron
DMT1 – divalent metal
transporter 1
DcytB – a ferroreductase
FPN – a ferroportin
Hephaestin – a ferroxidase
Tf - transferrin
Calcium
Ca++ is actively absorbed in all intestine segments
Calcium
transporter
Anti-porter
Vitamin D increases Ca++ transport across apical membrane and it
increases calbindin and Ca++ ATPase levels
IMCal – intestinal membrane calcium-binding protein
Vitamin B12
TCI – transcobalamin I
Pancreatic
proteases
TCI
Salivary glands secrete TCI which binds and protects B12 from stomach
acid until duodenum where pancreatic proteases degrade TCI enabling B12
to bind IF. TCII- B12 complex enters portal circulation
Fluid
• 9L absorbed/day
• Most important ions are
Na+ and Cl-
• Transcellular/paracellular
transport
• Neural & hormonal
regulation
Electrolytes
What gets excreted
What gets excreted
Composition
75% water 25% solids
Solids : Cellulose & indigestible fiber
Dead bacteria
Inorganic matter
Fats
Desquamated cells, mucus, enzymes
Stercobilin & urobilin
Odor due to bacterial products