Download Digestive physiology

Digestive physiology
Digestion and absorption
Gastric circulation and motility
Pre-ruminant GI development
Digestion and absorption
• These are related but separate
• Digestion: breakdown of complex molecules/nutrients into simple
molecules
• Absorption: process of transporting simple molecules across intestinal
epithelium
• Both are a result of biochemical events occurring in the gut
• Both are important for nutrient assimilation
• No absorption if food not digested
• Digestion fruitless if no nutrient absorption
• Various assimilation disturbances exist
• Caused by a variety of diseases
Digestion and absorption
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Some diseases affect digestion while others absorption
But signs often similar
Therapies might be different
Diagnosing cause is a challenge
Diarrhea occurs if there’s mismatch btwn secretion and
absorption
Microanatomy of SI
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SI mucosa has large surface area
Has epithelial cells with ‘leaky’ junctions btwn them
Facilates contact btwn SI mucosa & luminal contents
3 levels of surface convolutions serve to expand surface area
– Plicae circulares: large folds of mucosa, not present in all spp
– Villi: finger-like projections in epithelium, present in all spp, increase
SA 10-14 times
– Brush border: submicroscopic microvilli, further increase SA
• Base of villi has gland-like structures k.a. crypts of Lieberkuhn
Microanatomy of SI
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Villi & crypts covered with continuous layer of cellular
epithelium
Epithelial cells covering villi & crypts = enterocytes
Enterocytes have two distinct cell membranes
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Apical membrane covers cell surface facing lumen (apex)
Contains microvilli
Covered by jelly-like layer of glycoprotein k.a. glycocalyx
Enzymes & other proteins attached to MV & project into
glycocalyx
Basolateral membrane
Not in direct contact with ingesta
Absorbed nutrients exit enterocytes thru basolateral
membrane
Microanatomy of SI
• Attachments btwn adjacent enterocytes = tight junctions
• Not necessarily tight at molecular stand point
• Junctions form narrow band attachment btwn adjacent
enterocytes near apical end
• Allows free passage of water & some electrolytes
• Lateral space btwn lateral surfaces of enterocytes
• Distended & filled with ECF
• ECF separated from fluid in the intestinal lumen by tight
junctions
• & from blood by basement membrane capillaries
Microanatomy of SI
• Both tight junctions & capillary endothelia are permeable
barriers
• Allow free passage of water & small molecules
• Thus there’s relatively free flow of water & most electrolytes
btwn SI lumen fluid & ECF in lateral space & blood
Intestinal surface microenvironment
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Made up of glycocalyx, mucus & unstirred water layer
Goblet cells interspaced btwn enterocytes secrete mucus
Mucus covers mucosa
At brush border surface mucus blends with glycocalyx
Form viscous coating that trap molecules near apical
membrane
• Near intestinal surface in the unstirred water layer
• These form diffusion barrier thru which nutrient pass thru
before entering enterocytes
Digestion
• Involves physical & chemical breakdown
• Physical breakdown results in
– Reduction in feed particle size
– Allows food flow thru GIT
– Increases surface area exposed to enzymes
• Begins with mastication
• Completed by grinding action of distal stomach
• Physical action in stomach aided by chemical actions –
enzymes (pepsin) & HCl
• Chemical action breaks connective tissue
Digestion
• Physical breakdown complete when feed leaves stomach
• Chemical digestion accomplished thru hydrolysis
• Hydrolysis = splitting chemical bond by insertion of water
molecule
• Such bonds are
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Glycosidic linkages in CHO
Peptide bonds in proteins
Ester bonds in fats
Phosphodiester bonds in nucleic acids
• Enzymes catalyze hydrolysis
Digestion
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Enzymes are of two general classes
Those that act within lumen of gut
Those that act at membrane surface of epithelia
Lumen enzymes
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Originate from GI glands like salivary, gastric & pancreatic glands
Thoroughly mixed with ingesta
Actions thruout lumen of associated segments
Catalyse luminal phase of digestion
Results in incomplete nutrient hydrolysis
Results in short chain polymers from original macromolecules
Digestion
• Membrane surface enzymes
• Complete the hydrolytic process
• Enzymes chemically bound to surface epithelium of
SI
• Break short chain polymers to monomers
• Monomers absorbed across epithelia
• = membranous phase of digestion
• Followed by absorption
Summary
• Luminal phase
– Large polymeric molecules (starch & protein)
– Enzymes active in gut lumen (from salivary, gastric &
pancreatic glands)
• Membranous phase
– Small polymer molecules (polysaccharides, peptides)
– Enzymes active at surface of gut (synthesized in
enterocytes & attached to apical membrane
– Result in monomeric molecules for absorption
(monosaccharides, amino acids)
Absorption
• Movement of products of digestion across intestinal mucosa
into vascular system for distribution
• Need to understand
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Processes of diffusion
Differences in composition of ICF & ECF
Electrical polarity across membranes
Na+, K+ ATPase pump
Selective ion channels
• Uses specialized nutrient transport systems
• Exist in apical & basolateral membranes
• Involve specific proteins embedded in membranes
Absorption
• Proteins provide transport pathway
• Interact with specific organic nutrients & inorganic ions to
effect their transport across membranes
• Transport mechanisms classified as
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active,
secondary active,
tertiary active and
passive
Absorption
• Active transport
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Involves direct consumption of metabolic energy – ATP
ATP expended to move ions/molecules against electrical/chemical gradient
Na+,K+-ATPase pump important transport pathway
Lies in basolateral membrane
• Secondary & tertiary active tranport
– Utilize transcellular Na+ ion electrochemical gradient as source of energy
• Passive transport
– Occurs either thru ion channels in cell membranes
– Or directly thru the tight junctions
Regulation of GI function
• Diverse & specialized processes take place in different
sections
• Fundamental consistency in anatomy of the GIT
• Composed of 4 basic layers/tunics
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Tunica serosa
Tunica muscularis
Tunica submucosa
Tunica mucosa
• Mucosa most variable in structure & function
Regulation of GI function
Regulation of GI function
Regulation of the GI function
• Proper function of DS requires robust mechanisms for control &
communication
• Maintaining adequate control requires participation of both nervous &
endocrine systems
• GIT has built in versions of both
• DS control is complex
• Many DS diseases are associated with dysfunction of the relationship
• Regulation of GI function achieved thru
– Enteric/Intrinsic NS
– Enteric/intrinsic ES
– Motility of GI
Enteric/Intrinsic nervous system
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Exerts influence on motility, ion transport & GI blood flow
Control partly emanates from connections btwn DS & CNS
DS also has its own local NS k.a. enteric or intrinsic NS
ENS has immense complexity and magnitude
Has as many neurons as the spinal cord
Principal components are two networks/plexuses of neurons
embedded in GI wall
• Extend from esophagus to anus
Intrinsic NS
• Intrinsic motor nerves innervate
– Vascular muscle
– Gut muscle
– Glands in gut wall
• Gut smooth muscle innervation different from skeletal
muscle
• No direct synaptic junction btwn GI nerve & muscle
fibres
• Axons end in vesicular structures (varicosities)
• Contain neuroregulatory transmitter substances
Intrinsic NS
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Secreted by nerves in response to action potential
Affect actions of nearby muscles or glandular cells
Either inhibitory or stimulatory
Gut also receives extrinsic innervation from ANS
Parasympathetic & sympathetic NS form link
Link btwn intrinsic NS &CNS
Enteric nervous system
• Myenteric plexus
– Located btwn longitudinal & circular layers of muscle in the
tunica muscularis
– Exerts control primarily over GI motility
• Submucous plexus
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Buried in submucosa
Senses env within lumen
Regulate GI blood flow
Control epithelial cell function
Sparse and missing in some sections where these functions are
minimal such as the esophagus
• There are also minor plexuses beneath serosa
Enteric nervous system
The arrangement of the enteric
plexuses, depicted for the small
intestine. A: appearance in separated
layers. The myenteric plexus, consisting
of numerous ganglia and connecting
nerve fibre bundles, lies between the
longitudinal and circular muscle layers. A
second ganglionated plexus is in the
submucosa. These plexuses provide
nerve fibre plexuses in the muscle, in the
mucosa and around arterioles. B: The
enteric plexuses shown in a cross
section of the intestine
Enteric nervous system
• Enteric plexuses have three types of neurons –
sensory, motor & interneurons
• Sensory neurons
– Receive info (sensory input) from receptors in
mucosa & muscle
– Different types identified
– Respond to mechanical, thermal, osmotic and
chemical stimuli
Enteric nervous system
• Mechanoreceptors (muscular layers)
• Monitor distension
• Chemoreceptors (mucosa)
– Monitor chemical conditions in lumen
• Thermal
– Monitor temperature
• Osmotic
– Monitor ion concentration
Intrinsic NS
• Motor neurons
– Control motility & secretion, possibly absorption
– Have large # of effector cells – smooth muscle,
secretory cells, GI endocrine cells
• Interneurons
– Integrate msg from sensory neurons & provide it
to motor neurons
Enteric nervous system
• Uses various neurotransmitters
• Acetylcholine is the major one
– Generally neurons using Ach are excitatory.
– Stimulate:
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smooth muscle contraction,
increases in intestinal secretions,
Release of enteric hormones and
Dilation of blood vessels
• Norepinephrine also used extensively
– Derives from extrinsic sympathetic neurons
– Effect is almost always inhibitory
Enteric nervous system
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Functions autonomously
But note digestive fxn require communication links with CNS
Parasympathetic & sympathetic fibers connect CNS & ENS
Or connect CNS directly to GIT
Thru this gut provides sensory info to CNS & CNS can affect GI
function
• Signals from outside DS relayed to DS e.g. sight of appealing
food stimulates stomach secretions
Read more
• http://www.scholarpedia.org/article/Enteric_
nervous_system
Extrinsic Innervation
• Most of GIT receives parasympathetic innervation from vagus
nerve
• Part of terminal colon innervation thru pelvic nerve
• Preganglionic fibers synapse on cell bodies of intrinsic system
• Extrinsic sympathetic fibres enter gut thru post ganglionic
fibres
• Sympathetic fibres synapse on neurons of INS
• Others have direct effect on GI muscles & glands
Enteric/Intrinsic endocrine system
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Hormones from many endocrine glands affect DS fxn
Most profound effect from enteric hormones
GIT is largest endocrine organ in the body
Three hormones best studied are gastrin, CCK & secretin
EES is diffuse with single hormone-secreting cells scattered in
mucosa
E.g. stomach G cells are scattered among epithelial cells
Hormones synthesized within cells & secreted into blood
Hormones secreted in response to fairly specific stimuli
Endocrinocytes respond to changes in env within DS lumen
Their apical border is in contact with lumen & continuosly
‘taste’ luminal env
Enteric endocrine system
• Illustration of control: SI
– Ingesta from stomach = acidic
– SI is basic
– Presence of acidic ingesta stimulates secretin
secretion
– Secretin stimulates basic pancreatic secretions
that neutralize SI lumen contents
• ENS & EES interrelated
Intrinsic endocrine system
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Extensive # & variety of endocrine cells
Usually grouped together into gland
GI endocrine cells thruout gut epithelium
Broad base & narrow apex
Narrow apex exposed to lumen
Sample luminal contents
Secretory granules in base
Storage form of hormones
Intrinsic endocrine system
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Anatomy allows sensing lumen changes
Respond by releasing hormones
H released into mucosal area
Absorbed in blood stream
Not secreted into gut lumen
Each E cell has characteristic distribution
E.g. gastrin producing cells mostly in distal stomach
Cholecystokinin PC in SI esp proximal region
Major GI hormones
Hormone
Site of
production
Action
Release
stimulus
Gastrin
Distal
stomach
1o: stimulates acid secretion
from stomach glands
2o: gastric motility; stomach
epithelium growth
Protein in
stomach; high
gastric pH;
vagal
stimulation
Secretin
Duodenum
1o: bicarbonate secretion from Acid in
pancreas
duodenum
2o: biliary bicarbonate sec
Cholecystoki
nin (CCK)
Duodenum - 1o: enzyme secretion from
ileum
pancreas
2o: inhibits gastric emptying
Proteins &
fats in SI
Major GI hormones
Hormone
Site of
production
Action
Release
stimulus
Gastric
Duodenum +
inhibitory
upper
peptide (GIP) jejunum
1o: inhibits gastric motility
& secretory activity
2o: stimulates insulin
secretion if sufficient glc
present
CHO & fats in
SI
Motilin
1o: regulates motility
patterns btwn meals
2o: may regulate tone of
lower esophageal
sphincter
Acetylcholine
Duodenum +
jejunum
Gastric motility & emptying
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Entry of feed in stomach
Organ relaxes by reflex
Process of receptive relaxation
Triggered by pharynx & esophagus movement
Peristaltic contractions follow
Mix & squirt feed into duodenum
Controlled rate
Peristaltic wave, most marked in distal stomach
When well developed occur 3/min
Gastric motility & emptying
• Rate of emptying into duodenum depend on
feed type
• CHO rich feed leaves stomach in few hrs
• Protein –rich feed leaves slowly
• Slowest emptying with meal containing fat
Regulation of gastric secretion &
motility
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Under neural & humoral mechanisms
Neural: local autonomic reflexes
Involve cholinergic neurons & impulses
From CNS thru vagus nerve
Humoral: hormones e.g. gastrin, CCK
Vagal stimulation increases gastrin secretion
Some vagal fibers direct stimulation of fundus cells
Increase acid & pepsin secretion
Regulation of gastric secretion &
motility
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Gastrin & Ach potentiate each other
Cephalic, gastric & intestinal influences
Overlap
Cephalic influences
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Vagally mediated responses
Induced by CNS
Presence of feed in mouth – reflex gastric secretion
Sight, smell, thought in humans
Emotional responses –
anger/hostility –hypersecretion;
fear/depression – decrease sec, inhibit motility, blood flow
Regulation of gastric secretion &
motility
• Gastric influences
– 1o local reflex response
– Response to gastrin
– Feed presence accelerates secretions
– Stomach wall & mucosa receptors
– Respond to stretch & chemical stimuli
– Stimuli mainly aa & related products
Interaction of NS, ES & stomach
during gastric phase
Nervous system
Food in
stomach
Stomach
G cells
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+ Chief
cells
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Parietal
cells
Pepsinogen
HCl +
+
Pepsin
Gastrin
Protein
Peptides
Regulation in the stomach
• HCl activates pepsinogen – pepsin
• Pepsin formation stimulates more pepsin
production
• Experiment
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A. pepsinogen + ptn
B. pepsin + ptn
C. ptn + HCl
D. pepsinogen + HCl + ptn
E. pepsinogen + pepsin +ptn
Regulation of gastric secretion &
motility
• Intestinal influences
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Reflex & hormonal feedback effects
Initiated from SI mucosa
Gastric protein digestion products in duodenum
Stimulate gastric secretion from duodenal mucosa
Fats, CHO & acid in duodenum inhibits secretion & motility
• Other influences
– Alcohol & caffeine act directly on mucosa
– Moderate amounts +ve effects on appetite & digestion
– Stimulatory effects on gastric secretion
Absorption
• Substances pass thru lumen of GIT into circulation
• Different ways
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Diffusion
Non-ionic diffusion
Facilitated diffusion
Solvent drag
Active transport
Endocytosis
Summary
• Digestion & absorption depend on mechanisms that:
– Propel feed thru GIT
– Soften feed
– Mix feed with bile & digestive enzymes
• Mechanisms involve
– Dependence on intrinsic properties of intestinal muscle
– Operation of visceral reflexes
– Action of hormones
Hunger contractions
• Stomach musculature rarely inactive
• After emptying, mild peristaltic contractions
begin
• Gradual intensity increase
• More intense, mildly painful
• Associated with hunger sensation
• Interaction with feeding & satiety centres in
brain
Vomiting
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Visceral reflex
Starts with salivation & nausea sensation
Glottis closes
Prevents vomitus aspiration into trachea
Contraction abdominal wall muscles
Increase intra-abdominal pressure
Chest in fixed position
Esophagus & gastric cardiac sphincter relax
Reverse peristalsis begins
Vomiting
• Gastric contents ejected
• Vomiting centre in medulla oblongata
regulates
• Stimulated by
– upper GIT mucosa irritation
– Chemoreceptors stimulated by circulating
chemical agents
– Emotionally charged stimuli e.g. smells, sight
GI circulation and motility
GI motility
• Muscle contractions & motility are integral parts of digestive
fxn
• There are two fundamental patterns of motility
• Propulsion principally thru peristalsis
• Mixing thru segmentation contractions esp in SI
• These facilitate digestion and transportation of ingesta
GI motility: peristalsis
GI motility: mixing
GI motility
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Continuous contractions occur
The faster the contractions the faster the ingesta movements
More contractions when feeding than at rest
Amplitude of contractions vary
GIT Motility
MMC
FSM
GI circulation
Heart
Liver
Stomach
Spleen
Pancreas
Small intestine
Colon
GI circulation
• Main arteries
– Celiac – stomach, spleen, part of pancreas
– Hepatic - 1/3 of blood flow
– Superior mesenteric – SI, part of pancreas of LI
– Inferior mesenteric – main supply to LI
• Veins
– Portal vein - Drains blood from GI
– PDV = portal drained viscera
– Hepatic vein drains nearly all splanchic blood
Intestine
• Most perfused tissues in body
– Each villi with own vein and artery
– 50-60% blood to liver & SI
• PDV receives 30-35% of total cardiac output
• Increase in dietary intake increases flow to PDV
– Increased cardiac output
– %PDV remains relatively constant
• 75% to mucosa & submucosa – very metabolically
active
• 25% to muscularis & serosa
Counter-current mechanism
• Allows water/solute to pass from arteriole to
venule without passage through capillary bed
• Arteriole <20 µm from venule
• Vasculature has limited permeability
– Na+ cannot pass without transporter
– H2O & O2 can pass
Water & Na+ Absorption
• Na+ actively absorbed by SI to absorb water
from lumen
• Water movement allows follows Na+ via
osmotic gradient
• Water moves out of arteriole to venule due to
Na+ gradient created from venule to arteriole
• Increased Na+ conc in arteriole pulls water
from lumen