Download Cell Bio/Physio Exam 1 Outline Lecture 1

Cell Bio/Physio Exam 1 Outline
Lecture 1-Organization of the GI System I
 The GI tract is a disassembly line.
 Absorbed nutrients are used for fuel and repair.
o Molecules provide the energy to drive cellular processes
o Molecules represent the building blocks for cell growth and repair.
 Basic Steps of Digestion
o Ingestion
o Digestion-breakdown of ingested products into molecules
o Absorption-uptake of molecules by digestive epithelium
o Compaction-absorption of water consolidates indigestible residue into feces.
o Defecation
 Digestive system consists of the digestive tract and accessory organs.
 Digestive Tract
o Hollow, muscular tube extending from mouth to anus (GI tract is used
synonymously, but refers to stomach and intestines only)
o ~5m in life but may double in length after death due to loss of muscle tone.
o Oral cavity is the site of food intake, analysis of ingested material is also
performed in the oral cavity.
o Feeding behavior is controlled by the hypothalamus
 Digestion
o Breakdown of food into components which can be absorbed by the body,
done by mechanical or chemical.
o Mechanical digestion comprises the physical processes of crushing and
shearing, these occur from the mouth to the small intestine.
 Purpose is to ease swallowing and movement of solid foods
 Increases surface area of ingested food which facilitates chemical
digestion.
o Chemical digestion is a series of enzymatic reactions that break down
macromolecules into monomers.
 Occurs along the length of the GI tract but is predominant in the
intestine.
 Initiated by sight, smell and taste of food.
 Oral Cavity
o Mechanical digestion through chewing and initiates breakdown of food.
o Chemical digestion of both lipids and carbohydrates.
 Lipid digestion begins with lingual lipase
 Carbohydrate digestion is initiated by salivary amylase.
 Pharynx and Esophagus
o Muscular tubes that serve as conduits from the mouth to the stomach.
o No digestive enzymes are secreted by the pharynx or esophagus, but
enzymes do travel with food from mouth.
 Stomach
o J-shaped muscular sac in the upper abdomen
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o Links the esophagus to the small intestine
o Temporarily stores food, and continues mechanical and chemical digestion.
o Initiates chemical digestion of protein
o Digestion results in chime, a semifluid mixture of partially digested food.
Small Intestine
o Coiled mass filling most of the abdominal cavity inferior to the stomach and
liver.
o Longest part of digestive tract
o The length provides for principle and final site of chemical digestion, and
primary site of nutrient absorption
Large Intestine
o Begins at the terminal part of the ileum and ends at the anus.
o Functions to:
 Reabsorption of water, compacting food into feces
 Absorbs key vitamins liberated by bacterial action
 Storage of fecal matter prior to defecation.
Accessory glands and organs add secretions to the hollow organs to aid in digestion
and absorption and aid in mechanical digestion (teeth and tongue)
o Salivary glands-initiate digestion, lubricate food, cleans mouth and inhibit
bacterial growth.
o Liver and Gallbladder
 Liver produces and secretes bile (fat emulsifier)
 Bile is stored and concentrated by the gallbladder.
o Pancreas
 Secretes pancreatic juice
 Contains digestive enzymes for all the macromolecules
 Contains bicarb which buffers stomach acids.
Primary Role of the digestive system is preparation of foods for use by body cells.
Additional roles-fluid and electrolyte balance and immune function
o Fluid/Electrolyte balance-GI tract represents main source of fluid and
electrolyte intake.
 Represents a potentially significant route for loss of
fluids/electrolytes
o Immune Function
 Many lymphocytes and other immune cells are located along GI tract
in two main non-encapsulated forms
 Scattered diffuse-Mucosa-associated lymphatic tissue (MALT)
 Organized into nodules/follicles (Peyer patches)
 Lymphatic tissue defends against pathogens and develops
immunological tolerance to dietary substances and friendly bacteria.
Regulation of GI Function
o Unlike CV or respiratory systems, the GI tract is quiet or inactive between
meals.
o Response to food
 Detection of food and composition
 Coordinated movement of food through the tract
 Secretion of various fluids
 Control of blood flow to the tract
o Control
 Response of the GI tract to food is coordinated/regulated in two ways:
neurally and hormonally
o Neural Regulation
 GI tract consists of four layers histologically:
 Mucosa (epithelium, lamina propria and muscularis mucosa)
 Submucosa
 Muscularis externa
 Serosa (visceral peritoneum)
 Intrinsic nervous system
 GI tract has its own intrinsic nervous system called the Enteric
Nervous System
 Creates space and location advantages
 GI tract can’t function without the ENS and cannot function
properly with pathologies of the ENS (causes retention of
feces)
 ENS lies entirely in the wall of the gut, has no cell bodies in
brain or spinal cord
 Begins in esophagus and runs to the anus
 ~100 million neurons, thousands of small ganglia
 Ganglia are organized into two plexuses:
o Submucosal plexus (in the submucosal layer)-found
only in the small and large intestine. Controls the
function of the mucosa, tiny segment by tiny segment
o Myenteric plexus (in between the circular and
longitudinal muscle layers)-mainly promotes muscle
activity along the length of the gut to move food along.
 Some neurons are inhibitory which permits
opening of certain sphincters.
 At least a dozen different neurotransmitters are known to be
secreted by the enteric nervous system
o Acetylcholine generally excites GI activity
o Epinephrine and norepinephrine generally inhibit GI
activity
 Extrinsic nervous system (autonomic nervous system)
 ENS can operate independently of the brain or spinal cord,
some GI functions are highly dependent on extrinsic
innervation.
 Parasympathetic Nervous System
o All parasympathetic nerve fibers arise from brainstem
and sacral spinal cord.
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o Parasympathetic nerve fibers supplying the digestive
system arise from both locations
o CN X supplies GI organs from the esophagus to the first
half of the large intestine. 75% of parasympathetic
fibers are carried in the vagus nerve.
o Sacral parasympathetics are carried by the pelvic
splanchnic nerves, which supplies the distal half of the
large intestine all the way to the anus.
o Preganglionic parasympathetic fibers synapse with
enteric postganglionic fibers in the wall of the organ.
Then effector cells are controlled by the ENS.
o Parasympathetic stimulation causes a general increase
in the activity of the entire enteric nervous system,
which is reflected by increased glandular secretion and
motility.
Sympathetic Nervous System
o Sympathetic nerve fibers arise from the
intermediolateral gray matter of T1 to L2
o Sympathetic fibers to the GI tract originate in the spinal
cord between segments T5 and L2, these fibers
innervate the GI tract equally.
o Preganglionic sympathetic fibers synapse with
postganglionic fibers in the prevertebral ganglia.
o Postsynaptic fibers reach the end organ along the major
blood vessels and their branches. Some may innervate
the blood vessels and glands directly, while others may
synapse in the ENS.
o Sympathetic stimulation inhibits activity of the GI tract.
 Minorly norepi directly inhibits muscularis
externa activity
 Majorly norepi inhibits the entire ENS.
Sensory Nerves
o GI tract is richly supplied with sensory nerve fibers.
 Fibers conveying pain sensations
 Fibers conveying reflex sensations
o Reflex Sensation
 Carried by visceral afferent fibers, generally do
not reach the level of consciousness.
 Used to provide specific gut information
resulting in specific motor commands.
 Fibers carrying reflex info also have cell bodies
in the inferior vagal ganglion and the dorsal root
ganglia.
 Some may have cell bodies in the ENS.
Stimulated mechanically by stretch of smooth
muscle and chemically by changes in pH,
osmolality, or concentration of specific nutrients.
o Short Reflexes
 Integrated entirely within the ENS. They
coordinate local responses to local stimuli, the
arrival of a food bolus may cause local peristalsis
and glandular secretion.
 Short reflexes provide most of the control
required for normal GI function.
o Long Reflexes
 Utilize some aspect of extrinsic innervation
 Two forms: reflexes involving other parts of the
GI tract, and reflexes involving the CNS
 GI Tract reflexes
 Reflexes from one area of the gut to the
prevertebral ganglia and back to another
part of the gut.
 These reflexes are designed to protect
against large increases in tone and
intraluminal pressure.
 I.E.: colon is full, signals stomach and
small intestine to slow down.
 CNS Reflexes
 Reflexes from the gut to the spinal cord or
brainstem and back to the GI tract.
 Many of these reflexes can be mediated
entirely by the vagus nerve (vagovagal
reflex)
 Enterogastric reflex
o Chyme from stomach fills
duodenum, stretching walls.
o Sensory signals are integrated in
the brainstem resulting in
diminishing parasympathetic
impulse to the stomach.
 GI tract also under control of higher CNS centers,
i.e. fight-or-flight response. Sight and smell of
food can increase gastric acid secretions.
o Hormonal Regulation
 Digestive tract produces at least 20 hormones that affect almost every
aspect of digestive function.
 Produced and secreted by enteroendocrine cells of the epithelium in
response to various stimuli.
 Endocrine-uses the bloodstream to travel to target cells
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Paracrine-not secreted into the blood and targets nearby cells.
 GI tract and accessory organ glands
 GI tract and accessory organ smooth muscle
 Organs not directly associated with digestion and absorption.
Lecture 2-Organization of the GI System II
 GI tract is extensively supplied with smooth muscle, allowing motor activity which is
crucial for proper GI function.
o Individual smooth muscle fibers are arranged into parallel bundles.
o Organized into two layers, circular and longitudinal
o Within a bundle, smooth muscle fibers are extensively coupled electrically by
gap junctions. Bundles are separated by connective tissue but still fuses at
many points. Results in a latticework of smooth muscle bundles causing each
muscle layer to function as a syncytium.
o A syncytium is essentially a multinucleate cell. Results in any action
potential elicited anywhere in the muscle mass is very rapidly propagated.
 May travel length and breadth of the gut and between circular and
longitudinal layers.
 Contraction occurs in coordinated fashion, which results in peristalsis.
 GI Smooth muscle
o Excitation occurs through slow waves and action potentials.
o Slow Waves
 Refers to the cyclical variations in the membrane potential of GI
smooth muscle cells.
 Slow waves are not action potentials, however they are the prelude to
action potentials
 Cause of slow waves is not well understood.
 Modified smooth muscle cells (interstitial cells of Cajal) are
thought to act as pacemakers for smooth muscle cells, similar
to the heart muscle.
 Interstitial Cells of Cajal (ICC)
 Found from esophagus to large intestine, located primarily in
between the longitudinal and circular muscle layers
 Physically interposed between enteric nerve terminals and
smooth muscle and receive modulatory input from the CNS
and ENS.
 Electrically coupled to each other and to smooth muscle cells
via gap junctions forming extensive networks.
 Generate slow waves and impart slow wave activity to smooth
muscle cells via gap junctions.
 Loss of ICC function results in numerous GI motor disorders.
 Rhythm of most GI contractions is determined by slow wave
frequency.
 Slow wave frequency corresponds to GI contraction frequency.
o Spike (action) potentials
Two forms of action potentials in smooth muscle. Spike and plateau
(prolonged for sustained contractions, i.e. ureter).
 As the resting membrane potential of GI smooth muscle cycles, the
peaks approach -40mV, when the membrane potential exceeds -40mV
a typical action potential occurs.
 The greater the slow wave potential, the greater the frequency of
spike potentials.
 Slow wave potential is a result of Na+ influx; Ca2+ influx results in
spike potential.
 GI action potentials last 10-20 msec, which allows for a more
sustained contraction which produces a smoothly increasing level of
tension.
o Excitation-Contraction Coupling
 Slow waves that are not accompanied by action potentials, elicit little
or no contraction of the smooth muscle cells.
 Much stronger contractions result from action potentials, but some
muscle tone is elicited by slow wave potentials.
o Resting Membrane Potential
 Can be modified by external stimulation.
 Depolarization-factors include stretching, acetylcholine from
parasympathetic nerves and stimulation by GI hormones.
 Hyperpolarization-epinephrine/norepi, NO and ATP.
o Phasic Contractions-rhythmic contractions associated with both circular and
longitudinal muscle.
o Tonic contraction-sustained muscle contractions associated with all smooth
muscle.
 Circular and longitudinal smooth muscle have a baseline tension
called tone, occurs even in absence of spike potentials.
 Sphincteric muscle contracts tonically.
 Closure of sphincters is the common state, can last for minutes
and hours.
 Tonic contraction is an inborn property, not result of neuronal
input.
 Basal sphincteric tone is mediated by constant calcium influx
 Relaxation of sphincters is mainly mediated by NO release by
parasympathetic fibers or certain ENS fibers.
 Sympathetic activation of sphincters tends to induce
contraction of smooth muscle.
o Overall function of GI tract and smooth muscle is in response to neural input.
However, many other stimuli may cause contraction/relaxation in smooth
muscle cells.
Functional Types of Movements
o Propulsion
 Basic movement of the GI tract is peristalsis, which propels food along
the tube in a caudal direction.
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Peristalsis consists of waves of muscular contractions resulting form
the alternating actions of circular and longitudinal smooth muscle.
 Behind the bolus, circular muscle is contracting, longitudinal
muscle is relaxing.
 In front of the bolus, circular muscle is relaxing and
longitudinal muscle is contracting.
 Stimulus for peristalsis is distension of the gut.
o When a food bolus collects at any point in the gut, the
stretching stimulates the ENS to contract 2-3 cm behind
that point.
o Other stimuli include chemical or physical irritation and
strong parasympathetic input.
o Mixing
 Represents the churning of food.
 Differ in different parts of the alimentary tract.
 In some areas peristaltic contractions cause most of the mixing,
especially close to sphincters.
 Segmentation is the process that churns and fragments a food bolus,
causing mixing.
 Result of segmental contractions of circular muscle. Does not
propel bolus.
o Sphincter Activity
 Six sphincters in GI tract: upper esophageal sphincter, lower
esophageal sphincter, pyloric sphincter, ileocecal sphincter and
internal and external anal sphincters.
 Function to regulate movement of material.
 Segregates GI tract by function, permits organs to act as
reservoirs.
 It helps control one-way flow of luminal contents.
GI Blood Flow
o Arterial blood supply to the abdominal region derives from aorta and its
branches.
o Portal Circulation
 GI tract along with spleen and pancreas are drained by a separate
venous circulation called portal circulation.
 Portal vein returns blood from the GI tract to the liver first (before
going to the heart) which removes bacteria, and immediately
processes many nutrients.
 Blood from the liver then drains into the IVC.
o Rest of the abdomen is drained by tributaries emptying directly into the IVC
o GI blood flow is greatest flow of any system, ~25% of cardiac output.
o Flow to the GI tract serves multiple purposes
 Meet metabolic needs imposed by secretion and absorption, 80% of
blood flow is to mucosa.
 Transport of nutrients, hormones, water, and waste
 Maintain defensive integrity of mucosal barrier.
o Increased blood flow to GI tract is reflexively triggered by sight, smell, taste
of food; local chemical and mechanical stimulation, and oxygen deficiency.
o Two main targets for blood flow regulation in the GI tract, with submucosal
arterioles and capillaries.
o Mediators of Blood Flow
 Humoral
 In response to varying local conditions the gut mucosa releases
various vasodilator substances
o Cholecystokinin, vasoactive intestinal peptide, gastrin
and secretin
o Kinins-kallidin and bradykinin
 Neural
 Neural vasoconstriction in the gut results solely from
sympathetic input.
 Neural vasodilation is the gut is modulated in three ways
o Intrinsically-ENS (short reflex)
o Extrinsically-parasympathetic input (long reflex) and
afferent neuron itself.
Lecture 3-Cephalic, Oral and Esophageal Phases
 Cephalic Phase
o Activation of the GI tract in readiness for the meal, based on cognitive input,
thinking about food, olfactory, visual, and auditory.
o Increased parasympathetic outflow
 Increased salivary secretions
 Gastric acid secretion
 Pancreatic enzyme secretion
 Gallbladder contraction
 Relaxation of the sphincter of Oddi
 Oral Phase
o Same responses as cephalic phase, increased parasympathetic outflow.
o Contact with food elicits additional responses
 Additional increase in salivary secretions
 Swallowing reflex
 Subsequent esophageal motility responses
o Chewing breaks up food and begins mixing food with enzymes to start
breaking down starches and lipids. Very little absorption in the mouth.
o Salivary Glands
 Parotid, submandibular and sublingual glands.
 Exocrine glands, structure is tubuloalveolar.
 Acinar cells-secretory cells of the gland
 Serous (watery) cells, abundant in endoplasmic reticulum,
zymogen granules (store enzymes), and amylase (breakdown
starch).
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Mucous cells-mucin droplets, produces mucin which is
essential for lubrication and protection.
Salivary glands are classified based on acinar portion.
 Parotic-primarily serous, secretes amylase, water and
electrolytes.
 Submandibular-mixed serous and mucous
 Sublingual-primarily mucous
Functional unit is salivon, which is made of the acinus and associated
ductal system. 3 kinds of ducts
 Intercalated-secretory granules, drain acinar fluid into larger
striated ducts.
 Striated-columnar cells modify ionic composition of the saliva
and empty into larger excretory ducts.
 Excretory-columnar cells make additional changes in ionic
concentration, singular large duct coming from each gland and
drain into the mouth.
o Saliva
 Composition: low osmolarity, high K+ content, high organic content
 Rate-large flow rate relative to mass, ~30mL/h
 Primary secretion by acinar cells and intercalated ducts.
 Electrolyte composition resembles plasma and is isotonic.
 Secretion is driven by Ca2+ dependent signaling and opening
of apical Cl- channels in acinar cells. Cl- movement into the
ductal lumen creates the initial electoral chemical gradient
driving ion movement.
 Secondary (final) secretion
 Striatal and excretory ducts.
 Hypotonic, relative impermeability of ductal epithelium.
 Net absorption of ions by the ductal epithelium, creates a
hypotonic solution.
 At a slow rate the primary secretion is changed a lot by passing
through ducts, eventually creating a hypotonic solution. At faster
rates the primary secretion does not get altered much because it is
moving faster.
 Functions to initiate lipid and starch digestion, reduces friction,
moisten oral cavity for speech, and dissolve food to release flavor and
stimulate taste buds.
 Role in oral hygiene and immunity
 Bicarb helps neutralize acid in the moral cavity, prevent acidic
damage to teeth.
 Enzyme present to help kill bacteria.
 Immunoglobulins present helps play a role in mucosal
immunity.
 Hypotonicity of saliva aids in lysing HIV-infected leukocytes
o Salivary Gland Stimulation
Acidic foods are a potent stimulus
Smelling food and chewing
Inhibited by fear and some drugs.
Maximal stimulation can result in the parotid gland increasing from
400 mL/h to 1 mL/min/g of gland.
o Salivary Gland Regulation
 Parasympathetic
 Increase electrolyte and amylase
 Increase acinar and ductal cell activity
 Control center in medulla oblongata
o CN IX to otic ganglia to parotid gland
o CN VII to submandibular gland and sublingual gland
 Increase blood flow to glands, one of the very few places this
occurs
 Increase glandular metabolism and growth
 Sympathetic
 Increase mucous secretion
 Preganglionic thoracic nerves synapse in the superior cervical
ganglion
 Innervate acini, ducts and blood vessels
 Short-lived, smaller increases
 Beta receptors
Pharyngeal Stage-swallowing
o Functions to propel food form the mouth to stomach, inhibits respiration,
prevents entry of food into the trachea, and initiates primary peristalsis in
the esophagus
o Voluntary phase-tongue separates a bolus of food, thrust up and back and
initiates swallowing reflex.
o Pharyngeal phase, occurs in <1 second.
o Reflex Sequence Regulation
 Stimulation of touch receptors in the pharynx stimulates swallowing
center of the medulla and lower pons.
 Return motor impulses to pharynx and upper esophagus: CN IX, X and
XI.
 Esophagus body and lower esophageal sphincter innervated by CN X.
Esophageal Phase
o Three regions: upper esophageal sphincter, esophageal body, lower
esophageal sphincter
o Upper 2/3 of esophagus is striated muscle, lower 1/3 is smooth muscle.
o Functional Anatomy
 One of the only two places in the GI tract that has striated muscle, two
muscle layers including circular and longitudinal.
o Function is to propel food and sphincters protect airways during swallowing
and protect esophagus from gastric acid reflux
 Primary peristalsis is initiated by act of swallowing.
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Secondary peristalsis is initiated by distention caused by failed
transport or due to acid reflux.
o Regulation
 Extrinsic reflex-vagus afferents to the brainstem
 Nucleus ambiguous efferents via CN IX, X and XI, control
striated muscle
 Dorsal motor nucleus efferents via the vagus nerve, control
smooth muscle.
 Intrinsic reflex-results of mechanosensitive stimuli
 Peristalsis of striated and smooth muscle, relaxation of the LES
and proximal portion of the stomach.
o Changes in Esophageal Pressure
 Basal state-esophageal muscles are relaxed and the lower esophageal
sphincter is tonically contracted
 Presence of food bolus in the pharynx causes UES to open and LES to
relax
 Stimulation of the pharynx by swallowing relaxes the LES and
proximal portion of the stomach, readying the LES and stomach to
receive the bolus.
 Occurs with each swallow, and allows accommodation of large
volumes without raising the intragastric pressure.
 Resting esophageal luminal pressure is ~0 mmHg, inspiration results
in a negative intraesophageal pressure, increases LES and intragastric
pressure.
o Esophageal Disease
 Diagnosis is done with manometry, catheter with multiple pressure
sensors is used to measure pressure along esophagus.
 Incompetent LES
 Acid reflux
 Chronic exposure can cause GERD.
 GERD increases risk of developing Barrett’s esophagus, in
which damaged cells transform into metaplastic cells.
Precursor to carcinoma.
 Dysphagia-difficulty swallowing
 Failure of pharynx, esophageal body peristalsis, or failure of
LES to relax.
 Symptoms include inability to swallow.
 ‘Nutcracker Esophagus’-dysphagia associated with high
amplitude pressure waves as measured by manometric
catheters. Symptoms include angina-like chest pain.
 Achalasia-smooth muscle sphincters fail to relax, usually due to loss of
ENS inhibitory control. Caused by an inflammatory ENS disease.
 LES achalasia-liquid and solid food dysphagia without chest
pain.
 Diagnosed with manometric catheter.
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Corkscrew esophagus
 Diffuse esophageal spasms.
 Manometric measurement shows a simultaneous contraction
of entire esophageal body.
 Barium swallow shows a contorted esophageal body
(corkscrew esophagus)
 Often seen with achalasia.
Lecture 4-Gastric Phase I
 Stomach
o Functions
 Reservoir
 Mixing and the formation of chyme-initiate protein digestion
 Emptying
o Anatomy
 Regions: cardia, fundus, corpus, and antrum
 Functional regions
 Proximal (gastric reservoir)-fundus and 1/3 corpus
 Distal (antral pump)-2/3 corpus, antrum and pylorus
o Gastric Mucosa
 Columnar epithelium folded into gastric pits, each pit is a duct for
stomach glands.
 Surface epithelium cover entire surface
o Gastric Glands
 Oxyntic glands
 Most abundant gland in stomach, acid secreting.
 Located above gastric notch
 Parietal (oxyntic) cells secrete hydrogen chloride and
intrinsic factor
o Hydrochloric Acid
 Release stimulated by gastrin, Ach and
histamine.
 Converts pepsinogen to pepsin, aids in protein
digestion, helps kill bacteria/pathogens in food.
o Intrinsic Factor
 Release stimulated by gastrin, ACh, and
histamine
 Absorbs cobalamin (Vitamin B12)
 Endocrine cells
o Enterochromaffin-like cells secrete histamine into
surrounding tissues
 Histamine
 Release stimulated by Gastrin
 Stimulates parietal cell secretion via H2
receptors.
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o D cells secrete somatostatin
 Chief (peptic) cells secrete pepsinogen, located at base of
gland.
o Pepsinogen
 Release stimulated by ACh
 Converted to active pepsin in the stomach, best
at pH of 3
 Protease to digest proteins.
 Becomes inactive at pH >5 (intestines)
Pyloric glands
 Located below gastric notch, secretes acid but functions more
in control and regulation.
 Mucous neck cells secrete mucous
o Release stimulated by ACh, forms a sticky protective gel.
 Endocrine cells
o G cells secrete gastrin into stomach
 Stimulated by ACh, and oligopeptides and
amino acids in the antrum (meal high in
protein can cause more acid release)
 Gastrin stimulates H+ and histamine release
o D cells secrete somatostatin into surrounding tissues
 Release stimulated by luminal acidity and
gastrin.
 Functions as a tonic paracrine restraint on g cells
and tonic restraint on parietal and ECL cells.
Additional Secretions
 Electrolytes
o K+ is always higher than plasma, vomiting can result in
hypokalemia.
o Na+ concentration is lower than plasma
o Cl- is a major anion
 Surface epithelial cell secretions
o Bicarbonate anion, release stimulated by eating and
prostaglandins. Provides alkaline barrier.
o Mucus release stimulating by eating, functions to
provide a gel layer to protect epithelium from gastric
environment
Mechanism of Parietal Cell Secretion
 Structures
o Tubulovesicular membranes contain H+/K+-ATPase
pump.
o Intracellular canaliculus-branching secretory system
connected to the luminal surface.
 Activation
o Tubulovesicular membranes fuse with the intracellular
canaliculus.
o Massive luminal surface exposure of proton pump.
o Pumps H+ against its concentration gradient, cytosolic
pH=7, luminal pH=1.
 Ion Exchange
o Basolateral CL- exchange with HCO3-, generates
cytosolic CL-gradient need for release through luminal
Cl channels.
o HCO3- released into bloodstream and maintains
cytosolic pH, counteracts H+ secretion on the luminal
side.
o Luminal K+ channels release K+ back into the lumen
following cytosolic build up from proton pump
activation.
o Both luminal K+ and Cl- are stimulated by increased
cAMP
 Regulation of Gastric Secretion
o Neural pathways-vagovagal
 Parasympathetic innervates via intrinsic
neurons. Causes increase of gastric secretion.
o Endocrine
 Gastrin stimulates gastric acid secretion
 Stimulates release of somatostatin
o Paracrine
 Histamine-stimulates gastric acid secretion
 Regulation of Parietal Cell Secretion
o Histamine stimulates H+ secretion, increases cAMP
o Prostaglandins and somatostatin inhibit H+ secretion,
inhibits adenylate cyclase decreasing cAMP
 Inhibition of Gastric Secretions
o Somatostatin inhibits gastric secretion
 Inhibition of parietal, ECL and G cell release
 Negative feedback loops inhibits gastrin release
when stimulated by gastrin.
 Inhibits parietal cell release when stimulated by
H+ in the antrum.
o Phases of Gastric Secretion
 Cephalic ~30-40% of secretion, CNS is stimulated. Vagal nerve
stimulates parietal and G cells which release H+, IF and gastrin.
 Gastric ~50-60% of secretion
 Distention-stimulates mechanoreceptors which stimulate
parietal cells through local ENS reflex and vagovagal reflex.
 Chemical-digested proteins stimulate gastrin release.
 Intestinal ~10% of secretions


Distention-proximal small intestine releases gastrin
Chemical-circulating amino acid stimulates parietal cells
directly
o Interdigestive Period
 Mostly mucus secretion, very little stimulation of oxyntic cells.
 Emotional stimuli-increase interdigestive gastric secretions by
oxyntic cells, nervous stomach and ulcers.
 pH of the stomach
 Between meals: 4-5
 During a meal: 1-2
o Intestinal Inhibition of Gastric Secretions
 Reverse enterogastric reflex stimulated by the presence of food in the
small intestine.
 Coordinated effect on gastric emptying.
 Releases secretin
 Released by S cells in duodenum
 Stimulated by acid (most important)
 Controls pancreatic secretion and inhibits gastric secretion.
o Gastric Digestion and Absorption
 Digestion
 Some digestion not necessary, intestinal digestion is sufficient.
 Some amylase digestion, low pH inactivates amylase
 Lipid digestion begins
 Absorption
 Very little
 Drugs-ASA, NSAIDs and alcohol
Lecture 5-Gastric Phase II
 Gastric Motility
o Electrical Activity
 Slow waves are always present, sets the pace.
 Gastric antrum, slow wave and action potential used interchangeably.
 GI smooth muscle depolarization is caused by activation of L-type
Ca2+ channels
 Ca-channel blockers can cause constipation
 Plateau phase is a balance of inward Ca2+ and outward K+ currents.
 Slow waves occur at different frequencies in different locations
(antrum, small and large intestines)
 Slow waves trigger AP, which trigger contraction. When AP are
associated with slow waves it occurs during the plateau phase.
 Interstitial Cells of Cajal generate the electrical slow waves in the
stomach, small intestine and large intestine. Form gap junctions with
both layers of smooth muscle.
o Functional Anatomy
 Functions to mix, propel, and store
Proximal (corpus and fundus)-storage and mixing
Distal (corpus, antrum and pylorus)-mixing and propulsion
Two Sphincter regions
 LES (cardia), relaxation allows food in and gas out
 Pyloric sphincter (gastroduodenal junction), regulates gastric
emptying, higher muscular tone and closed during gastric
phase.
o Proximal Gastric Motility
 Regulates gastric pressure and compliance
 Tonic contraction-does not contract phasically. Tone is important in
regulated gastric emptying.
 Low tone associated with delayed or slow gastric emptying.
 Maintains forces that push the contents into the antral pump.
 Regulated by ENS and vagal efferents
 Receptive relaxation-swallowing
 Receive food without increasing intragastric pressure
 Failure leads to bloating, epigastric pain and nausea.
 Adaptive relaxation-distention of gastric reservoir
 Vagovagal reflex, initiated by stretch receptors in stomach.
 Lost in vagotomy-lose vagal efferent relaxation, increased tone
and decreased wall compliance. Lowered threshold for
sensations of epigastric fullness and pain.
 Feedback relaxation-triggered by presence of nutrients in the small
intestine.
o Distal Gastric Motility (Antral Pump)
 Mixes food and propulsion
 Thicker muscle capable of phasic contractions. Contractions are ringlike and initiated in midportion of the stomach and move toward the
pylorus.
 Gastric action potentials determine the duration and strength of the
phasic contractions. Rate is set by ICC cells, strength set by ENS
neurotransmitters.
 Leading contraction
 Relatively constant amplitude
 Rising phase of the AP
 Close the pyloric sphincter
 Trailing contraction
 Follows lead contraction by a few seconds
 Variable amplitude
 Occurs when plateau phase is above threshold
 Retropulsion
 Occurs when the trailing contraction reaches the pylorus
 Increased intraluminal pressure causes a jet-like retropulsion
back through the orifice created by the trailing contraction,
reduces particle size.




o Regulation of Gastric Motility
 Vagovagal control-similar to gastric secretions
 Gastric stimuli activate vagal afferent activity to the medulla
 Distention-stimulates mechanoreceptors
 Chemical-digested proteins
 Vagal efferents elicit a response
 Proximal motility-inhibition of smooth muscle and reflex
accommodation, entry storage of food with little increase in
intragastric pressure
 Distal motility-magnitude of contractions is regulated by ENS
neurotransmitters.
Gastric Emptying
o Third function of the stomach, ensures proper delivery of nutrients to the
duodenum. Prevent overload and maintain proper absorption.
o Steps
 Increased tone in the proximal section (increased intraluminal
pressure)
 Increased strength of antral contractions
 Opening of the pylorus
 Inhibition of duodenal segmental contractions
o Rate
 Dependent on the macronutrient content of the meal and the amount
of solids.
 Liquids empty faster
 Lag phase-time required for grinding
o Regulation
 Under inhibitory control of the duodenum to prevent overloading sm
intestines. Allows for time to neutralize acid, dilute to proper
osmolality and digest foodstuff
 Stimuli (sensing food in the stomach and duodenum), increase proton
release.
 Hypotonic and hypertonic solutions empty slower than
isotonic solutions
 High caloric content decreases emptying, fat is emptied at the
slowest rate.
 Response
 Gastric phase response-slows gastric emptying
 Activates vagovagal reflex
 Mechanism
 Nutrients in the duodenum release cholecystokinin from
endocrine cells in the duodenum.
 Initiates vagovagal reflex-mediated decrease in gastric
emptying
 Once chyme has passed into the jejunum, inhibitory
mechanisms fade and stomach can empty.

Gastric Disorders
o Gastritis-secretory disorders and mucosal barrier breakdown
 Mucosal Protection and Defense
 Breakdown of mucosal barrier:
o Superficial breakdown with an effect on the submucosal
are erosions.
o Breakdowns effecting deeper layers of the muscularis
are called ulcers
 Harmful factors increasing the effects of H+
o Pepsin, bile and NSAIDs
o Others-EtOH, tobacco and caffeine
o H. pylori-gastric inflammation, ulcers and gastric
carcinoma
 Gastritis
 Erosive and hemorrhagic
o Etiology: NSAIDs, ischemia, stress, EtOH, trauma,
Zollinger-Ellison
 Zollinger-Ellison-increased gastrin production,
usually a tumor
o Leads to an acute ulcer, causing bleeding/and or
perforation
 Non-erosive, chronic active
o Antral gastritis
o H. Pylori infection
o Lead to ulcer development especially in presence of
other risk factors.
o Most common cause of ulcer
o Tx is antibiotics and PPI (clarithromycin, amoxicillin
and PPI)
 Atrophic (fundal gland)
o Autoantibodies attack parts and/or products of the
parietal cell
o May lead to endothelial metaplasia
o Pernicious anemia
 Cobalamin (Vit B12) deficiency
o Gastric motility disorders-rate dysfunction and sphincter dysfunction
 Too fast or two slow
 Too slow
 Delayed gastric emptying
 20-30% of pts with DM
o Vagal neuropathy, loss of adaptive relaxation-epigastric
pain and fullness. Loss of propulsive motility
 Pyloric stenosis-thickening of pyloric canal muscles. Usually
children (mostly males and first born)
 Surgery to correct.

Too Fast
 Surgical causes
o Distal stomach resection
o Pyloroplasty-elective surgery to open up the pyloric
canal and treat PUD
 Pyloric incompetence
o Reflux of bile acids-damage gastric mucosa, lead to
gastritis and ulcers.
Lecture 6-Exocrine Pancreas and Hepatobiliary Systems
 Exocrine Pancreas
o Function
 Secrete pancreatic enzymes
 Amylase-breakdown carbs
 Trypsin and chymotrypsin-breakdown proteins into
polypeptides
 Procarboxypeptidase-breakdown polypeptides into amino
acids
 Lipase-breakdown fats
 Neutralize acids
o Anatomy
 Pancreatic ducts
 Wirsung (major)-enters duodenum with the common bile duct
at sphincter of Oddi
 Santorini (minor)-enters duodenum proximal to Wirsung
 Sphincter of Oddi regulates flow of bile and pancreatic juice, prevents
reflux into the pancreatic ducts.
 Acini
 Acinar cells-enzyme producing cells
 Centroacinar cells-modify electrolyte content
 Ducts
 Duct cells-bicarb secretion, modify electrolyte content.
o Exocrine Pancreas Enzymes-all are synthesized in Acinar cells in forms of
zymogens and must be activated.
 Trypsinproteins to amino acids
 Chymotrypsinproteins into amino acids
 LipaseTGLs into FAs and glycerol
 Carboxypeptidasetakes off terminal acid group from a protein
 Elastasesdegrade elastin
 Nucleasesdegrade nucleic acids
 Pancreatic amylasestarch, glycogen and other carbs.
 Trypsinogen is released into small intestine, enterochinase turns
trypsinogen into active Trypsin.
o Electrolyte Secretions
 HCO3- and H2O neutralize HCL



Duct cells-electrolyte modification
Opening of CFTR Cl- channels, activated by increase in
cytosolic cAMP. CFTR dependent (pancreatic dysfunction in
CF).
 HCO3- is generated by Na+/HCO3- symporter and catalyzed
intracellularly by carbonic anhydrase. Bicarb originates in the
stomach, and then released into blood stream.
 Normally isotonic, but HCO3- increases 5 fold when stimulated.
o Regulation of Pancreatic Secretion
 Cephalic phase-enzyme secretion
 Gastric-vagovagal reflex
 Intestinal-most important, mostly hormonal. Effector cells include
ductal and acinar cells.
 Principal stimuli
 Ach and CCK stimulate enzyme secretion
 Secretin stimulate HCO3- secretion
 Regulation of Ductal Secretions
 Duct cells are stimulated by secretin, which is made in S cells in
the sm intestine.
 Effect-stimulate bicarb release
 Mechanism-increases intracellular cAMP
 Secretin is stimulated by duodenal pH <4.5
 Regulation of Acinar Secretions
 Acinar cell stimuli include ACh from vagus nerve and CCK
(primary) from I cells.
 Causes increased enzyme release
 Mechanism-increase intracellular Ca2+
 Source stimulus: ACh (vagovagal reflex) and CCK (long-chain
fatty acids, free amino acids)
 Additional Stimulants of CCK Release
o CCK-releasing peptide: paracrine cells sense fatty acids
and amino acids and release CCK-releasing factor
o Monitor peptide released by acinar cells into the gastric
juice
o Both CCK-releasing peptide and monitor peptide, may
be stimulated by neuronal input and help match CCK
release and subsequent pancreatic enzyme release to
the meal stimulus. These peptides are degraded once
the ingested meal has passed.
o Pancreatic Disease
 Cystic Fibrosis-mutation of CFTR Cl- channel. Causes meconium
illness in newborns. Results in thickened pancreatic secretions block
the pancreatic duct, which reduces digestive ability and results in
malabsorption disorder and pancreatitis.
Hepatobiliary System
o Function-produce bile (aids in digestion and absorption of lipids), store bile
and reabsorb bile.
o Anatomy
 Liver-hepatocytes produce bile
 Bile canaliculi are dilated intercellular spaces between
hepatocytes and drain into bile duct which leads to gallbladder.
 Gallbladder-stores bile
 Between meals the sphincter of ODDI is closed so the bile is
stored in the gallbladder, which absorbs H2O and concentrates
bile. Released into duodenum with eating.
 Ducts-right and left hepatic ducts combine to form common hepatic
duct, which empties into common bile duct and joins with the
pancreatic duct to form the Ampulla of Vater
 Sphincter of Oddi regulates flow.
o Bile
 Contents
 Bile salt-conjugated bile acid
 Bile pigment-bilirubin
 Lipids-cholesterol and phospholipids
 Proteins
 Function
 Digest lipids, emulsifying fats by forming micelles which
aggregates fat droplets and allows missing of lipids and bile
acids, then increase surface area which increases lipase action.
 Excrete bilirubin and cholesterol
 Gallbladder bile is highly concentrated compared to hepatic
bile.
 Bile Acids
 Produced in hepatocytes by cytochrome P450 oxidation of
cholesterol.
 Stored and concentrated in gallbladder
 Primary bile acids-cholic acid and chenodeoxycholic acid
 Secondary bile acids-conversion of primary bile acids by
bacteria in the gut: deoxycholic acid and lithocholic acid.
 Bile Salts
 Bile acids conjugated with glycine or taurine and forms a
complex with Na+. At neutral pH they are ionized, which limits
absorption. Conjugated bile acids require active carriermediated transport for absorption.
 Function-promote intestinal absorption of lipids, acts like a
detergent. And acts to excrete cholesterol.
 Bile Lipids
 Cholesterol-cholesterol gallstones
 Phospholipids-phosphatidylcholine
 Bile Flow





Canalicular bile flow and ductular secretion
Canalicular Bile flow
o Bile acid-dependent secretion
 Energy dependent.
 Bile salts are taken up by the hepatocytes, new
bile salts synthesized from cholesterol.
 Cholesterol and phospholipid secretion is
coupled to bile salt secretion.
o Bile acid-independent secretion
 Energy dependent
 Secretion of HCO3 Ductular Secretions
o Secretions include H20 and bicarb
o Effected by CFTR mutations, thickening of the bile
secretions can result in obstruction
Bile Acid Regulation
 Highly regulated, prevents toxicity to GI lining.
 Synthesis and secretion is regulated by the amount of bile acid
in the hepatic portal circulation.
o Negative-feedback system
o Between meals-low concentrations of bile salts in the
portal blood, results in high synthesis
o After meal-high concentrations of bile salts in portal
blood inhibits bile acid synthesis.
Bile Release
 Similar to pancreatic regulation, cephalic, gastric and intestinal
phases.
 Cephalic and gastric phases are the same as pancreatic
secretions.
o Increased parasympathetic outflow results in
gallbladder constriction and relaxation of the sphincter
of Oddi.
 Intestinal phase is primarily regulated by GI hormones
 CCK stimulated by amino acids or free fatty acids in duodenum.
o Effect-gallbladder contraction, Oddi relaxation.
Stimulates vagovagal reflex.
 Secretin-just like pancreas, stimulated by acidic chyme.
o Effect-Bicarb secretion from duct cells
 Additional Regulators
o Gastrin-stimulates bile acid secretion, direct effect on
liver. Indirectly increase acid which results in increased
secretin.
o Steroids (estrogen and androgen)-inhibit bile secretion
Enterohepatic Circulation
 Recycling of Bile Salts-occurs in small intestine and liver.
o All bile acids=total bile acid pool=2-4 grams.
 Absorbed bile salts return to hepatocytes via portal vein,
attached to albumin and HDL.
 Absorption of Bile Salts
 Passive diffusion-entire small intestine, small amount
 Active carrier-mediated-most important, very efficient
 Passive diffusion following deconjugation by bacteria-forms
bile acids
 Passive diffusion following dehydroxylation by bacteria-forms
secondary bile acids; deoxycholic acid is absorbed while
lithocholic acid is poorly absorbed.
o Bilirubin
 Major pigment in bile-orange color
 End product of hemoglobin degradation, transported in blood bound
to albumin.
 3 important hepatic processes
 Remove bilirubin from blood
 Conjugation with glucuronic acid
 Excreted into bile canaliculi
 Deconjugated to urobilinogen (reabsorbed), urobillin (excreted), and
stercobilin (excreted, brown color).
o Disease
 Cholelithiasis (gallstone)-imbalance in the bile, either too much
cholesterol or too little bile salts. Can form anywhere in biliary tree.
Causes jaundice, pancreatitis, colic, acute cholecystitis, more prevalent
in women.
 Jaundice-increase in unconjugated bilirubin in the plasma, causes
yellowing of the skin and conjunctiva. Caused by liver disease, and
bile duct blockages.
 Cholestasis-blockade of bile flow, disruption of bile flow through the
canaliculi. Results in jaundice, deposition of cholesterol and pruritus.
Lecture 7-Integrated Response to a Meal I
 Small Intestine
o Structure
 Absorptive surface is amplified by villi, folds, and microvilli.
 Enterocytes and goblet cells originate from stem cells
 Stem cells are located in the bottom of crypts
 As cells mature they migrate to the tops of crypts.
 Rapid proliferation affected by GI hormones, growth factors, presence
of food, starvation and surgical resection. Rapid turnover makes
these cells vulnerable to radiation and chemotherapy.
o 3 types of Digestion
 Luminal-luminal enzymes
 Membrane-brush border enzymes

 Intracellular-intracellular proteases
o Process of Absorption
 Location
 Stomach-limited absorption
 Small Intestine-primary and only real site for the digestion of
food
 Colon-limited, mainly water and electrolyte absorption.
 Transport
 Occurs across a number of cellular barriers, from fluid layers to
a number of membranes.
 Absorption-pinocytosis, diffusion, facilitated diffusion, and active
transport
 Adaptation-resection and bypass surgery initially impede absorption.
Hyperplastic changes result which allow for adaptation
 Assimilation=digestion + absorption
Carbohydrate Digestion
o Breakdown of complex molecules are accomplished using molecules of H2O.
o Structure
 Cellulose-straight glucose polymer, non-digestible with beta-1,4
linkage
 Starch-straight glucose polymer, digestible with alpha-1,4 linkage
 Glycogen-branched glucose polymer, digestible with alpha-1,4 and
alpha 1,6 linkages.
 Oligosaccharides
 Disaccharides-sucrose and lactose
 Monosaccharides-glucose and fructose
o Luminal Digestion
 Carbohydrate digestion in the mouth and stomach occurs via amylase,
actively secreted and breaks down alpha-1,4 bonds.
 In the mouth accomplished with salivary alpha-amylase, breaks down
starch to digested maltose.
 In the small intestine accomplished with pancreatic alpha-amylase.
More efficient than salivary amylase, completes starch digestion to
maltose.
o Membrane Digestion
 Action of three enzyme complexes generates several
monosaccharides:
 Lactase: lactosegalactose + glucose
 Lactase deficiency results in inability to breakdown lactose.
Causes diarrhea, cramps and flatus.
 Lactose is fermented by colonic bacteria.
 Treatment by eliminating dietary milk intake.
 Maltase and alpha-dextrinase: maltoseglucose + glucose
 Sucrase: sucrosefructose + glucose
o Disorders of Carb Digestion Pt 1
Congenital lactose intolerance-ingestion of breast milk or formula
results in diarrhea. Must avoid lactose formula and breast milk.
 Congenital sucrose (is maltase deficiency)-autosomal recessive,
intolerance for starch and sucrose. Treat by avoiding sucrose and
starch.
o Carbohydrate Absorption
 Transport of glucose and galactose across the apical membrane via
the Na+/Glucose symporter
 Driven by Na+ gradient
 Reinforced by a baso-lateral sodium-potassium pump.
 Requires D-configuration or six-membered pyranose ring.
 Transport of fructose via the furanose transporter; Na+
independent, found mainly in jejunum.
 Transport of glucose, galactose, and fructose across basolateral
membrane via the glucose/fructose/galactose symporter
 Mediated by facilitated diffusion of all three monosaccharides.
 Driven by concentration gradient
 Disorders
 Congenital Glucose/Galactose malabsorption results in fluid
secretion and osmotic diarrhea. Caused by mutation of SGLT1.
Treat by avoiding glucose, galactose and lactose. Infants must
be fed with fructose.
Dietary Fiber
o No digestion of vegetable fiber, but results in bulk. In low fiber diets,
infrequent bowel movements results.
o Bulk laxatives increase the volume of indigestible material in the colon.
Protein
o Structure-dietary proteins are chemically long chains of amino acids bound
together by peptide bonds.
o Enzymes Location
 Luminal Enzymes
 Multiple Brush-Border Peptidases-affinity for larger oligopeptides
 Cytoplasmic di- and tri-peptidases-intracellular proteins
o Digestion Pathways
 Luminal proteases from stomach and pancreas
 Proteins + peptides  AA  absorbed
 Luminal proteases then brush border enzymes
 Proteins  peptides & peptides  AA  absorbed
 Luminal proteases then cytoplasmic enzymes
 Proteins  peptides  absorbed
 Absorbed peptides  AA  transported to blood
 Luminal proteases
 Proteins  peptides  absorbed  transport to blood
o Digestion Enzymes



Gastric and pancreatic enzymes are zymogens (pro-enzymes) and
activated in the lumen.
 Stomach enzymes are not essential.
 Pepsin-mediated digestion in stomach, first secreted as
pepsinogen by chief cells. Converted to pepsin by stomach
acid.
 Most pancreatic zymogens are activated by trypsin.
 Trypsinogen secretion stimulated by CCK. Trypsinogen converted to
trypsin by enterokinase, trypsin can also self-convert trypsinogen to
trypsin.
 Endopeptidases-cleave peptide bonds adjacent to specific AAs, result
in oligopeptides. Types: trypsin, chymotrypsin and elastase
 Exopeptidases-cleave peptide bonds adjacent to the carboxyl
terminus, result in individual AAs. Types: Carboxypeptidase A and B.
Apical Absorption of Peptides
 Transported into enterocytes using the PepT1 symporter. H+
dependent and important for uptake of di-peptide antibiotics.
 Once inside the cell peptides are hydrolyzed to individual AAs by
cytoplasmic peptidases.
 PepT1 is advantageous over single AA transporters because it is nonselective and can simultaneously uptake a number of AAs compared
to single transporters.
Brush-Border Digestive Enzymes
 Substrate specific
 Aminopeptidase: N-terminal  AA
 Dipeptidase: Dipeptides  AA
 Dipeptidyl aminopeptidase: N-terminal  dipeptide
 Dipeptidyl Carboxypeptidase: C-terminus  dipeptide
 Cytoplasmic peptidases are distinct di- and tri-peptidases internal to
the cell.
Absorption of AAs at the Apical and Basal Membrane
 Almost all peptides and proteins are digested into AAs via brushborder peptidases or cytoplasmic peptidases.
 At least 7 distinct AA transporter systems are located on the apical
membrane with overlapping affinities.
 Almost all are Na+ dependent, driven by action of baso-lateral
sodium-potassium pump.
 Rare absorption of larger proteins and peptides can cause serious
allergic or immunologic responses.
Source of Intracellular AAs
 Uptake across the apical/basolateral membrane from the lumen and
blood.
 Hydrolysis of oligopeptides which enter via the apical membrane.
 10% of absorbed AAs are used for intracellular protein
synthesis.

o
o
o
o


o Basolateral transport of AAs
 At least 5 antiporter systems at the baso-lateral membrane.
 To blood (cell  blood): 3 AA antiporters
 From blood (blood  cell): 2 AA antiporters for cell nutrition
 Crypt cells are the origin of intracellular AAs absorbed from the
blood.
o Defects of Apical AA Transport
 Hartnup’s Disease-autosomal recessive, both small intestine and renal
tubule abnormalities.
 Defective transport of neutral AAs from the lumen across the
apical membrane. Resulting decrease in NAD, niacin, serotonin
and melatonin synthesis.
 Treatment-Eliminate high protein diet.
 Cystinuria-autosomal recessive, both small intestine and renal tubule
abnormalities
 Defective absorption of cysteine and basic AAs
 Impairment in cysteine reabsorption resulting formation of
cysteine kidney stones.
 Treatment is eliminate cysteine in diet.
o Defects of Baso-lateral AA Transport
 Lysinuric Protein Intolerance-rare inherited disorder
 Defect in baso-lateral transporter which results in impaired
cationic AA transport across membrane.
 Characterized by malnutrition, impaired immune response,
osteogenesis imperfect
 Renal reabsorption of lysine is affected.
 Cannot be treated with dipeptide/high protein diet.
GI Bacteria
o Virtually no bacteria in the jejunum and ileum, due to presence of gastric acid
and rapid intestinal motility
o Large number of bacteria in the colon, significant mass in feces.
o Benefit
 Digestion of some cellulose
 Vit K, Vit B1 (thiamine), Vit B2 (Riboflavin), Vit B12 (Cobalamin)
o Disadvantage
 Exposure to ionizing radiation can result in overwhelming sepsis due
to destruction of immune defenses.
 Antibiotics must be administered to pts undergoing XRT.
Feces
o Composition
 75% water
 25% solid matter including bacteria, undigested material, fats,
inorganic matter and proteins.
o Considerations
 Unaffected by variations in diet.

 Large fraction of fecal mass is non-dietary in origin.
 Meconium is a newborn baby’s first feces.
Intestinal Gas
o Gas eliminated as flatus originates in three sources:
o Swallowed air
o Gas formed from bacterial action
o Gas that diffuse into the GI tract from the blood
o Bad odor originates from H2S and aromatic amines
o Composition of Gas
 Individual variation
 Sex variation
 Volume is 200-2000 mL/day
 Contains combustible gases, associated with explosions during
cautery involving intestine. Comes from fermented mannitol. Nonfermentable purgatives now used.
Lecture 8-Integrated Response to a Meal II
 Dietary Lipids
o Structure
 Polar-soluble in water
 Non-polar-insoluble in water, i.e. cholesterol
 Amphipathic-polar and non-polar, i.e. free fatty acids, TGL and
phospholipids
o Only source of essential fatty acids
o Impairment of lipid transport/intake leads to hypovitaminosis
o Consumption
 TGL: origin from plant and animal cell membranes
 Cell membrane phospholipids-plant and animal cell membranes
 Unesterified cholesterol-animal cell membranes
o Endogenous Lipid sources
 Bile-digestion and absorption of lipids, phospholipids and unesterified
cholesterol
 Membrane lipids-from desquamated intestinal epithelial cells
 Dead colonic bacteria
o Emulsification
 Essential for the effective action of digestive lipases, necessary as
lipases are more efficient at oil-water interfaces.
 Initiated by food preparation
 Facilitated by chewing, gastric churning, and retrograde movement of
fluid through the pylorus
 Involves coating of lipid droplets using bile acids, lecithin, membrane
lipids, denatured protein and cholesterol.
 Result of emulsion decreases in lipid droplet size, increase in oilwater interphases which supports the activity of lipases and forms
micelles.
o Digestion:
 Mouth-lingual lipase, no digestion
 Stomach-gastric lipase and swallowed lingual lipase, require a pH of 4.
Functions to begin the hydrolysis of triglycerides in mucous layer,
inactivates by increasing pH of the duodenum.
 Processing of resulting products:
 Long chain FAs-water insoluble, remain in droplet core and
absorbed by enterocytes
 Medium/short chain FAs-water soluble, passively absorbed in
gastric mucosa and enterocytes.
 Duodenum-presence of free fatty acids result in the release of CCK
from the duodenal mucosa.
 CCK increase results in increased bile secretion and increased
secretion of pancreatic enzymes.
 Pancreas-pancreatic lipase functions in the digestion of TGLs in the
presence of colipase, secreted as a zymogen and activated by trypsin.
Hydrolyzes ester bods and results in 2-monoglycerid and two fatty
acids.
 Regulation of pancreatic lipase
o Acts only at the oil-water surface of a lipid droplet
o Inhibited by presence of surface emulsifier components
o Co-enzyme required.
 Enzymes that Hydrolyze Lipid Esters
 Pancreatic Carboxyl Ester Hydrolase-breaks ester bonds of
cholesterol and glycerol esters producing free fatty acid and
free cholesterol or glycerol respectively
 Pancreatic Intestinal Phospholipase A2 (PLA2)-breakdown of
glycerophsopholipids
 Colonic bacterial lipases-non-specific and not inhibited by bile
salts.
o Absorption
 Formation of mixed micelles
 Lipases, bile salts, lecithin and cholesterol absorb to the
surface of emulsion droplets
 TGLs are transported to surface which stabilize the drop
 Lipases hydrolyze TGLs at the surface releasing long-chain FAs
resulting in the shorter-chain FAs containing TGLs moving to
the surface from the core.
 Hydrolysis of lipids resulting in multi-lamellar layer formation
 A piece of the droplet buds off forming a multi-lamellar vesicle,
additional action of lipase resulting in forming a unilamellar
vesicle
 Further addition of bile salts results in the formation of mixed
micelles.
 Transport of Free Fatty Acids Across Membrane


Mixed micelles carry FFAs which must cross 3 barriers:
intestinal mucus gel layer, unstirred water layer, and apical
surface of the enterocytes.
 Transport of Non-micelle FFA Monomers
 Absorbed into enterocytes following protonation by diffusion.
Bile salts from micelles return to lumen and are absorbed.
 Uptake of dietary FAs occurs 2 ways:
 FAs from the cellular lumen are transported into the blood
unchanged
 FAs are incorporated into TGLs intercellularly via the action of
the smooth ER and bound to fatty-acid binding protein. This
results in the formation of chylomicrons.
o Fatty Acid binding Proteins prevent reflux of long chain
FAs back into lumen, and prevent cellular damage by
free-floating intracellular FAs.
 Chylomicron Absorption
o Secreted by enterocytes into the blood via exocytosis
o Large majority pass into the blood capillaries and enter
the lacteals
o From there pass into the lymphatic system, enter the
lymphatic duct and pass into the venous circulation.
Water Soluble Vitamins and Minerals
o Cobalamin (Vitamin B12)
 Sources-meat, fish, eggs, dairy products, requires IF for absorption in
the ileum
 Functions
 Methyl transfer
 Krebs’ Cycle Intermediate conversion
 Deficiency-leads to accumulation of Methylmalonyl-CoA
 Following gastrectomy pts fail to absorb B12 efficiently from the
ileum due to the loss of the source of IF (parietal cells)
 Absorption
 Cobalamin is ingested with dietary meals
 Liberated from meat and other foods via pepsin
 Free cobalamin binds with protein haptocorrin to prevent
breakdown
 Pancreatic proteases liberate haptocorrin from cobalamin
 IF secreted from parietal cells is substituted for haptocorrin
 IF-bound cobalamin is absorbed in the terminal ileum by
enterocytes
 Endosome is fused with lysosome where IF is broken down by
proteolytic enzymes
 Cobalamin is transported to a secretory vesicle prior to the
destruction of IF

Cobalamin is bound to transcobalamin II and secreted into the
blood.
 Can take 3-4 hrs from brush border to lumen.
 Malabsorption can be from vegetarian diets, pernicious anemia,
impaired intestinal function, Crohn’s disease, and Ileal resection
 Malabsorption can be treated with IM/SQ administration of cobalamin
o Calcium Absorption
 Source from milk and milk products. Increased absorption with
pregnancy and decreased with aging.
 Types of Absorption
 Active Transport
o Occurs in Duodenum, regulated by Vit D.
 Passive Transport
o Small intestine, not vitamin D regulated
o Iron Absorption
 Dietary forms
 Non-heme iron and heme iron
 Sources in meat and vegetables, Fe3+ not readily absorbed
 Vitamin C reduces Fe3+ to Fe2+
 Iron is absorbed in the duodenum, only Fe2+.
 Mechanism
 Receptor-mediated endocytosis-transferrin receptor
 DCT1 Symporter-co-transported with H+
 Heme absorption-occurs via unknown mechanism
 Iron deficiency results in microcytic anemia, iron overload results in
hemochromatosis
 Hemochromatosis
 Inherited disorder, northwestern European ancestry. Most
commonly autosomal recessive.
 Mutation of the HFE gene
 Accumulated iron results in increased oxidative stress leading
to tissue damage.
 Can cause cirrhosis, DM, bronze skin pigmentation, HF,
cardiomyopathy, Vit D deficiencies, arthritis and infertility.
 Excess iron can trigger airport metal detectors
 Treatment is blood removal until plasma ferritin levels
normalize.
Lecture 9-Secretory Functions of the GI Tract
 Small Intestine
o Anatomy
 Villus cells-absorption of nutrients and electrolytes. Epithelial cells
secrete enzymes and have microvilli on their surface that allow for
multiplication.
 Very large surface area
Crypt cells-secretion of electrolytes and fluid, contain stem cells and
Paneth cells.
 Proliferation and migration of intestinal mucosal cells is continuous,
process occurs at the crypt base in both small and large intestine,
produced by stem cells. New cells migrate along the crypt-villus axis,
cells reach top of villi and slough off within 48-96 hrs
 Cell turnover decreased during starvation and increased during
lactation, post-intestinal resection and postprandial phases.
o Secretions
 Duodenum
 Contain alkaline mucus-secreting glands known as Brunner’s
glands. Stimulated by irritation, vagal stimulus and secretion
of secretin.
o Secrete mucus for physical protection of duodenal wall
and secrete bicarb for acid neutralization.
o Inhibited by sympathetic stimulation
 Jejunum and Ileum
 Secretion of the intestinal digestive juices occurs via the Crypts
of Lieberkuhn (located between the intestinal villi throughout
the small intestine.
 Contains:
o Goblet cells to secrete mucus for protection
o Enterocytes-secrete fluid and electrolytes at the crypt
level, and absorb fluid, electrolytes and nutrients at the
villi.
o Paneth cells are innate immune cells that provide
antimicrobial protection.
 Fluid is mostly isotonic, slightly alkaline and serves to
neutralize acid.
 Watery Fluid-process is unclear, believed to be the product of
electrochemical drag caused both cations and anions to be secreted
into the intestinal lumen. Water moving out of small intestine only
occurs by osmosis.
 Digestive Enzymes
 Enzymes are secreted or attached to cellular membrane (brush
border enzymes), regulated by tactile stimulation and local
enteric reflexes.
Large Intestine
o Anatomy
 Absence of Villi
 Surface epithelium absorbs electrolytes but does not secrete
electrolytes
 Crypts of Lieberkuhn-secretion of electrolytes, do not absorb
electrolytes.
o Secretions


Mucus Secretion
 Main product of secretion, regulated by tactile stimulation and
local enteric reflexes as well as Parasympathetic stimulation.
 Functions in feces formation and protection of the intestinal
wall.
o Diarrhea
 Primarily caused by the excess secretion of water and electrolytes in
response to irritation.
 Changes in secretion occur in order to protect against bacteria,
irritants, or adapt to other conditions.
 Mechanism
 Increased fluid secretion
 Increased smooth muscle motor activity
o Fluid and Electrolyte Absorption
 Nutrient absorption is an exclusive function of the small intestine.
 Fluid and electrolyte absorption is a function of both the small and
large intestines.
 Absorption mediated by a variety of transport mechanisms.
Amplification of Surface Area
o Small Intestine-increased surface area facilitates increased absorption,
translates to a 600-fold increase in surface area
 Level 1-folds of Kerckring, macroscopic organ level
 Level 2-Villi and Crypts-microscopic tissue level
 Level 3-Microvilli on apical surface of epithelial cells-submicroscopic,
cell level.
o Large Intestine-Increased surface area facilitates increased absorption
 Level 1-folds of Kerckring
 Level 2-crypts, no villi
 Level 3-Microvilli on apical surface of epithelial cells
Intestinal Absorption
o Small Intestine-Maximum absorptive capacity is 15-20 L/day
o Large Intestine-Maximum absorptive capacity is 4-5 L/day
 High compensatory potential for water absorption
Intestinal Electrolyte Movement
o Overall ion movement in any segment of the intestines is representative of
the summation of various absorptive and secretory events. These may be
paracellular or transcellular, may occur in the villi or crypts, and may be
mediated by goblet or absorptive cells.
o Na+ Absorption
 Nutrient-Coupled Absorption: very resistant to pathological changes
 Primary mechanism of Na+ absorption during a meal and soon
after the large meal.
 Apical-presence of glucose, galactose, and amino acids in the
lumen provides a gradient for the uptake of Na+





Baso-lateral-secondary active transport, fueled by Na+/K+
pump
 Located in small intestine.
 Parallel Antiporter Exchange
 Primary mechanism of Na+ uptake between meals.
 Apical-Na+/H+ and Cl=/HCO3- antiporters
 Baso-lateral-Na+/K+ pump
 Located in small intestine.
 Na+ uptake driven by activity of carbonic anhydrase due to
intracellular production of bicarb.
 Susceptible to pathological changes, transporters can be
inhibited by aldosterone.
 Epithelial Na+ Channels
 Apical-epithelial Na+ channels
 Baso-later-sodium-potassium pump
 Located in distal large intestine
 Susceptible to pathological or pharmacological changes.
o K+ sparing diuretics can affect this process
o Activity can be enhanced by aldosterone
o Cl- Absorption
 Voltage-Dependent Absorption
 Apical- Cl- channels
 Baso-lateral- sodium-potassium pump
 Driven by sodium transporter and postprandial transport of
sodium/glucose/AAs.
 Located in small and large intestine
 Neutral Antiporter Exchange
 Apical- Cl-/HCO3- antiporter
 Baso-lateral- sodium-potassium pump, Na+/H+ antiporter and
diffusion of CO2
 Located in large intestine and some parts of small intestine
 Susceptible to pathological changes, affected by rise in
intracellular enterotoxins.
 Parallel Antiporter Exchange
 Responsible for Cl- absorption during the interdigestive period
 Apical- Na+/H+ and Cl-/HCO3- antiporters
 Baso-lateral- sodium-potassium pump, osmosis of H2O and
diffusion of CO2
 Located in proximal large intestine and some parts of small
intestine
 Susceptible to pathological changes, affected by rise in
enterotoxins
 Congenital Cl- Diarrhea (Chloridorrhea)





Congenital absence of apical Cl-/HCO3- antiporter. Renal and
erythrocyte antiporters are unaffected
Results in increased Cl- in stool and increased plasma levels of
bicarb, leading to alkalosis.
Signs and symptoms-alkalosis, hypochloremia, CNS symptoms,
retarded growth and bowel distention.
o Cl- Secretion
 Electrogenic secretion of Cl- in the small and large intestine is
exclusively by crypt cells.
 Apical-Cl- channels
 Baso-lateral: Na+/K+/Cl- symporter, sodium-potassium pump, and
Na+ follows Cl- via paracellular path along with water.
 Susceptible to pathological changes, affected by rise in enterotoxins
and cAMP stimulation of apical Cl- channels results in diarrhea
 Dynamics
 Non-stimulated state results in decreased cAMP, decreased Clsecretion and channels are closed or absent.
 Stimulated state results in increased cAMP, increased Clsecretion and channel protein synthesis/open state.
o K+ Secretion and Absorption
 Gastrointestinal tract can absorb or secrete large quantities of
potassium. Absorbed in both small and large intestine, only secreted
in large intestine.
 Movement of potassium is paracellular, follows net movement of
water.
 Large intestine is major site for controlled K+ secretion
Regulation of Intestinal Ion Transport
o ENS-activation of secretomotor neurons, release of ACh and resulting active
Cl- secretion
o Endocrine Aldosterone (Na+ absorption of Na+ in large intestine)
 Renin-angiotensin activation (Na+ absorption)
o Paracrine Mucosal endocrine cells secrete serotonin and other peptide
hormones, stimulate adjacent epithelial cells.
o Immune cells
 Inflammatory cytokines are released from immune cells, results in
increased permeability of vascular membranes and expulsion of ions
and water into tissue and lumen
Water and Osmosis
o Water follows osmotic gradient produced mainly by Na+ and Cl- movement.
o Water enters the circulation from the intestines via two routes
 Paracellular pathway-around the cells
 Transcellular pathway-through the cells
o Diarrhea
Loss and/or active secretion of electrolytes into the lumen.
Electrolytes cause osmotic drag that attracts water, and water ends up
trapped in the stool.
 Leads to dehydration
o Constipation
 Increased absorption of electrolytes into the body from the lumen,
cause increase absorption of water.
Secretagogues-compounds that increase fluid and electrolytes in lumen of intestine.
o Bacterial exotoxins (Enterotoxins)
o Hormones and neurotransmitters-activation of intracellular mechanisms
including protein synthesis of Cl- Channels
o Immune Cell Products-histamine from mast cells increases vascular
permeability
o Laxatives-more in pharm
Absorptagogues-factors that stimulate the absorption of fluid and electrolytes
o Mineralocorticoids-act in distal colon to increase Na+ absorption and K+
secretion.
o Glucocorticoids-act in small intestine by activation of electroneutral Na+ and
Cl- absorption
o Hormones and Neurotransmitters
 Stimulate electroneutral Na+/Cl- absorption and inhibit bicarb
secretion, results in increased fluid absorption
Diarrhea
o Symptom of increased stool volume and mass.
o Results increased BM and loose stool
o Caused by
 Malabsorption of dietary nutrients
 Endogenous secretion of fluid and electrolytes
 Infections
 Inflammatory
 Long-standing diabetes-alternating with constipation, dysmotility due
to neuropathy
 Secretory-blood born tumors and bacterial products such as cholera
toxin. Bile acids can also damage secretory or absorptive apparatus of
luminal epithelium
 Chronic pancreatitis and liver cirrhosis
Oral Rehydration Solution
o Life saving for cholera, dehydration and metabolic acidosis
o Utilization of nutrient-coupled Na+ and H2O absorption
o Transporter is unaffected by the rise in intracellular levels of cAMP/cGMP or
Ca2+
o Increases in glucose or AA concentrations in the intestine will result in
increases in the absorption of Na+ and H20
o Solution made of glucose, sodium, chloride, and bicarb.






Lecture 10-Inegrated Response to a Meal III
 Small Intestinal Movements
o Mixing and Segmentations
 Distention of the small intestine stimulates localized and rapid
concentric contractions. Relaxations occur after the contraction.
 The results are chopping of the content and a sausage-like
appearance.
 Contraction is dependent upon the frequency of basic electrical waves
and myenteric stimulation (highly dependent)
o Propulsive
 Chyme is moved by peristaltic waves that move toward the anus at a
velocity of 0.5-2.0 cm/sec and dies out after traveling for 3-5 cm. Net
movement of chyme is 1 cm/min
 Movement can occur in both directions, but dies out more rapidly in
the oral direction due to polarization of the myenteric plexus in the
anal direction.
o Peristaltic Reflex
 Stretching of the intestinal wall during passage of bolus triggers a
reflex that constricts the lumen behind bolus and dilates ahead of it.
 Process controlled by interneurons.
 Cholinergic Type 2 motor neurons with prolonged excitation
simultaneously activate circular muscle fibers behind the bolus and
longitudinal muscles in front.
o Propulsive Control
 Ingestion increases peristalsis
 Stimulating Factors
 Stretch of the intestinal wall
 Gastroenteric reflex-stretch reflex of the stomach
 Gastrin, CCK, Insulin, Motilin and Serotonin
 Decreasing Factors
 Secretin and Glucagon
 Propulsive movements help spread chyme through small intestine.
Chyme remains in small intestine until the intake of the next meal
o Peristaltic Rush
 Presence of irritants and toxins in the intestine leads to peristaltic
rush characterized by powerful and massive contractions of the small
intestine. Does not occur in the large intestine.
 Motor Activity
o Stomach and Small Intestine
 Fasting state is characterized by rhythmic changes in electrical motor
activity contractions or migrating motor complexes.
 Migrating motor complexes (MMCs) have four distinct phases
 1. Prolong quiescent period
 2. Period of increased frequency of action potentials and
contractility

 3. Period of peak electrical and mechanical activity
 4. Period of declining activity
 Fasting and Fed States
 MMCs originate in the stomach and travel to the distal part of
the ileum.
 MMCs play an important role in elimination
o In the stomach food is pushed into the duodenum
o Small intestine undigested food, bacteria, desquamated
cells, and secretions are moved into large intestine.
 MMCs do not occur in the large intestine
 MMC Disorders
 Can be seen in a number of disease states: DM, pseudoobstruction, sclerodoma and ileus.
 In these cases the MMC is altered or weakened.
 Complications:
 Bezoar formation
 Intestinal bacterial colitis
 Excessive rapid small bowel transit time
 Nausea/vomiting
 Constipation
 Abd distension
Large Intestine
o Function
 Absorption of fluid and electrolytes (major)
 Absorption of short-chain fatty acids (minor)
 Reservoir function
 Elimination of fecal content
o Characteristics
 Motility is sluggish, no distinct fasting or fed patterns of contraction.
 Controlled by neurogenic, myogenic and hormonal signals
 Innervation
 Vagus nerve-proximal 2/3 large intestine (absorption)
 Pelvic nerves-descending and recto-sigmoid portion (storage)
o Motor Activity
 Proximal portion of large intestine is characterized by non-propulsive
mixing movements
 Segmental muscle contraction, circular muscle constrictions and
longitudinal muscle contraction.
 Results in mixing and rolling of content and formation of Haustras.
Functionally provides the intimate contact of fecal matter with colon
wall for absorption.
 Mid and distal portion of the large intestine performs mass
movements, which involves contractions of the larger segments of the
intestinal circular muscle.


Process beings at proximal transverse colon, with constrictive
ring forming.
 Several haustrations constrict simultaneously moving the
content ~20 cm distally
 Haustra disappear but then reappear after contraction
 Another distal contraction takes place, total duration is 10-30
min.
 Mass movements initiated by gastrocolic and duodenocolic reflexes
which occur from distention AND irritation
o Potassium
 Large intestine plays an essential role in the regulation of K+ levels in
the body
 Secretion is passive (paracellular) and active (pump-leak model)
 Passive secretion is driven by lumen-negative trans-epithelial
voltage
 Active secretion
o Baso-lateral: K+ uptake from blood via sodiumpotassium pump and Na+/Cl-/K+ symporter
o Apical: Apical K+ channels, rate-limiting step.
o Aldosterone enhances K+ secretion by increasing the
activity of the apical K+ channel
 Therapeutic Uses
o Because large intestine can secrete K+, it can be used in
pts with elevated K+ concentrations to lower those
levels.
o Administering an enema containing K+ binding resins
and non-absorbable carbohydrates (sorbitol) will cause
osmotic diarrhea resulting in colonic K+ loss
 Absorption is passive (paracellular) and active (H+/K+ antiporter)
 Absorption and secretion of K+ is location specific
 Proximal large intestine  absorption
 Distal large intestine  absorption and secretion
 Dietary effects on K+ regulation
 High dietary K+ enhances both passive and active K+ secretion
 Low dietary K+ results in active K+ absorption
Rectum
o Anatomy
 Defecation controlled by presence of two sphincters
 Internal anal sphincter
 Circular and longitudinal smooth muscle, high resting tone.
 Relaxation initiated by peristalsis
 External anal sphincter
 Striated muscle only
 Both voluntary and involuntary, kept continuously constricted
until consciously signaled

o Defecation
 Final stage of digestion resulting in expulsion of indigestible residues
from the body
 Achieved by coordinated action of the smooth and striated muscle
layers in the rectum and anus as well as pelvic floor muscles.
 Controlled by internal and external sphincters
 Reflexes
 Intrinsic reflex includes the peristaltic reflex and relaxation of
the internal anal sphincter
 Parasympathetic defecation reflex
o Stimulation of spinal cord segments at S2, cholinergic
fibers and pelvic nerves.
 Undesired Defecation
 Sequence:
 1. Mass movements fills rectum
 2. Unconscious relaxation of internal anal sphincter by NO
production
 3. Anal sampling
 4. Reflex contraction of the EAS
 5. Distention of rectum
 6. Reflex contraction of IAS causing increasing pressure
 Two Outcomes
o Reflex relaxation of the EAS-expulsion of feces in the
incontinent patient
o Conscious contraction of the EAS
 Desired Defecation Sequence
 1. Mass movement fills rectum
 2. Unconscious relaxation of the IAS
 3. Conscious effort-relaxation of the EAS
 4. Intra-abd pressure is raised to expel feces
o Deep breath moves diaphragm downwards
o Glottis closes + contraction of thoracic muscles
 5. Abd muscle contract
 6. Increased pressure enables the passage of feces through
relaxed sphincters
 7. Pelvic floor muscles relax which straightens rectum.
 Constipation
 Defined as slow movement of feces through the large intestine
associated with dry/hard feces in the descending colon.
 Caused by
o Obstruction of the movement of the colon
o Irregular bowel habits
o Overuse of laxatives
o Spastic colon
GI Obstruction


o Various causes, consequences depend on the point of obstruction in the GI
tract.
o Locations
 Proximal to Pylorus-causes persistent vomiting, acidic vomitus and
loss of H+
 Distal to pylorus-vomiting, loss of large amounts of water and
electrolytes, dehydration, neutral vomitus or basic vomitus with bile
 Distal end of large intestine-accumulation of feces for several weeks
with no vomiting, once colon is full severe vomiting begins.
Hirschsprung’s Disease (Megacolon)
o Associated with constipation, megacolon and narrowing of the rectal
segment of the colon.
o Caused by congenital absence of submucosal and myenteric plexi.
o Diagnostic signs include constipation and megacolon
o Mechanism-lack of relaxation of affected segment, backup of intestines, and
enlargement of colon
o Treatment-surgical excision of aganglionic segment required.
Vomiting
o Defined as reflex retrograde expulsion of GI content caused by excessive
irritation, over-extension, or rover excitation of GI mucosa.
o Initiated by strong stimulus such as distention or irritation
o Coordinated by vomiting center in medulla
 1. Vagal and sympathetic afferent impulses approach vomiting center.
 2. Efferent impulses exit via CN V, VII, X, XII and spinal nerves and
enter GI
 3. GI motor responses including the upper GI tract, diaphragm and
abdominal muscles play a role in process.
o Vomiting Reflex
 Antiperistalsis or reverse peristalsis starts prior to vomiting
 Antiperistaltic waves begin in ileum and push intestinal contents all
the way back into the duodenum and stomach
 Over-distention of GI tract initiates vomiting
o Stages of Vomiting Reflex
 1. Deep Breath
 2. Rising Hyoid bone and larynx
 3. Closing of glottis
 4. Closing of nares
 5. Contraction of diaphragm and abd muscles
 6. LES relaxes
o Control
 Chemoreceptor trigger zone located in the floor of the 4th ventricle
 Stimulated by Drugs (morphine and amorphine) and impulses from
vestibular apparatus (motion sickness)
o Complications
Vomit aspiration-gag reflex and coughing prevents occurrence,
inhibited by anesthesia and intoxication. Aspiration leads to chemical
aspiration pneumonia, severe pulmonary epithelium damage may
lead to death.
 Dehydration and Electrolyte imbalance-acute loss of H+, leads to
metabolic acidosis and loss of water.
 Mallory Weiss Tear-caused by forceful vomiting, defined by erosions
in the esophagus or small tears in the esophageal mucosa. Pts often
vomit bright red blood
 Destruction of enamel-acid destruction and with bulimia nervosa
o Nausea
 Defined as conscious recognition of excitation of an area of the
medulla closely associated with vomiting center.
 May or may not precede vomiting
 Stimuli-irritation impulses coming from the GI tract, impulses that
originate in the lower brain associated with motion sickness, and
impulses from the cerebral cortex to initiate vomiting.
