Digestion - Dr. Ann Wechsler Room 1135 McIntyre...

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Unformatted text preview: Dr. Ann Wechsler Room 1135 McIntyre (514)398-4341 ann.wechsler@mcgill.ca March 19 – April 11, 2008 PHYSIOLOGY OF THE GASTROINTESTINAL TRACT (GIT) AND ITS ACCESSORY STRUCTURES GIT Role in HOMEOSTASIS – provide nutrients External Environment DIGESTIVE SYSTEM Absorbable Molecules FOOD we will focus on what happens to the food when it enters the digestive system before it can be absorbed into the intestinal system INTERNAL ENVIRONMENT “Processed” Cells ENERGY & RAW MATERIALS Growth & Repair Function & Regulation GIT structure Ext.env. EARTHWORM Ext.env. - the digestive system is open at both ends - the central lumen is an extension of the external environment GROWTH two properties of the digestive tract: DIFFERENTIATION 1. Tubular Nature 2. Communication with External Environment GROWTH 1 - in a cadaver, the muscle elements of the digestive tract are relaxed and the length of the GIT increases by a factor of two - in a living human, the muscle tone shortens the overall length of the GIT Mouth 4.5m Stomach LENGTH of adult GIT Small Intestine Large Intestine Anus 1.5m GROWTH 2 Internal Surface area = 200-250 m2 LUMEN - the internal surface area is increased by 600x over the external surface area - this is achieved by villi, microvilli etc. - this increased surfaced area makes for increased absorption and the efficiency of transport DIFFERENTIATION - different portions of the digestive tract are specialized to perform specific functions - there is always communication with the external environment at both ends despite the differentiation - associated with the digestive tube are a number of accessory organs: salivary glands, pancreas, liver Pp 581 - 4 layers of identifiable tissue fibers are extended parallel to the long axis of the gut - when contracted, the length of the gut shortens Longitudinal fibres Circular fibres fibers are at right angles to the length of the tract - when contracted, the diameter of the lumen gets smaller striated LUMEN S M O O T H - most of the muscle in the GIT is smooth muscle - only the muscle near the mouth and pharynx are striated - the muscle from about 1/3 of the esophagus down is smooth striated SEROSA thin, tough layer of connective tissue MUSCULARIS EXTERNA double layer of muscle P 581 Longitudinal fibres Circular fibres Muscularis smooth mucosae muscle Lamina propria LUMEN layer of loose connective tissue Epithelial layer epithelial cells with secretory and absorbing properties MUCOSA made up of three layers SEROSA MUSCULARIS EXTERNA loose connective tissue with nerves lymphatics and blood vessels SUBMUCOSA GUT WALL STRUCTURE (mid-esophagus to anus) 1. Serosa – thin, tough layer of connective tissue (continuous in places with abdominal mesentery) 2. Muscularis Externa – outer layer longitudinal fibres (when it contracts, GIT shortens), inner layer circular fibres (when it contracts, lumen narrows); (musculature in oral cavity, pharynx, upper 1/3 esophagus and external anal sphincter is striated; the rest is smooth) 3. Submucosa – loose connective tissue, housing neuronal network, lymphatics, blood vessels 4. Mucosa – muscularis mucosae (sm. muscle) - lamina propria (loose connective tissue) - epithelial layer (secretory - exocrine and endocrine - and absorptive cells) GIT FUNCTIONS To convey food along GIT, allowing it to be disrupted into small molecules which can be absorbed into circulation. 3 Activities: 1. MOTILITY (muscular activity) Propulsion & physical breakdown Chemical Breakdown digestion in its truest sense 2. SECRETION (glandular activity) 3. ABSORPTION - Transfer to circulation DIGESTIVE / ABSORPTIVE EFFICIENCY CARBOHYDRATE FAT PROTEIN 99% 95% 92% - most of what we ingest, we digest and absorb - we can absorb much more than we are capable of eating in a normal day Pp 588-590 how are we able to be so efficient in digestion and absorption? PROPULSIVE – SECRETORY– ABSORPTIVE ACTIVITIES integrated for high functional efficiency by NEURAL and HORMONAL MECHANISMS ENTERIC INNERVATION (ENS) - the digestive system has its own neural system INDEPENDENT, INTEGRATIVE NERVOUS SYSTEM of the CNS, autonomic system - you can separate the gut from the brain and you will still have fundamental neural control INITIATES PROGRAMS REGULATES COORDINATES activities of muscular and secretory elements GUT WALL INNERVATION lumen - the enteric nervous system exists as a large number of neurons and associated fibers that are collected into ganglia - the ganglia are further collected into two plexuses - the submucosal plexus of meissner and the myenteric plexus of auerbach (located between the two muscle layers) - there are interconnections between the two plexuses - it contains everything necessary for reflex arcs - receptors (osmo, pH, mechano, chemo) - sensory fibers that carry information to other ganglia - large number of effector neurons - large number of interneurons - important for the coordination of the muscle - stimulating one sensory neuron can coordinate both muscular and secretory activity - an interneuron can activate effectors at a distance from the original stimulus - some interneurons are inhibitory - as a result of some reflex arcs, inhibitory neurons can be activated - the two plexuses are anatomically distinct - they are too many interconnections between them that it is difficult to distinguish different functions serosa The ENS consists of the myenteric plexus (between the longitudinal and circular muscle layers) and the submucosal plexus. Though anatomically distinct, the two plexuses behave as a functional unit, which includes all the elements required for reflex arcs: sensory neurons, effector neurons, and interneurons. ENS consists of ganglion cells and their processes which synapse with sm.muscle cells, endocrine and exocrine cells, and other ganglion cells. Some of the enteric neurons are excitatory (release mostly ACh – acting on muscarinic receptors -); others are inhibitory (release NANC (Non Adrenergic, Non Cholinergic transmitters). Also present are enteric sensory fibres with cell bodies in plexuses. - an enteric neuron is excitatory (orange) releases Ach and acts on muscarinic receptors (can be blocked by atropine) - some enteric neurons are inhibitory (yellow) do not release Ach or NE, but a neurotransmitter NANC - non-adrenergic-non-cholinergic, e.g. NO - there can be a variety of levels of activity which depends on the sum of all the excitatory and inhibitory impulses Secretory Cell intraneural SHORT REFLEXES G U T W A L L Chemoreceptors, osmoreceptors, mechanoreceptors sensory input bringing information from the gut, enteric layers integration of information modification of activity of smooth muscle Nerve plexus Smooth Muscle or Gland Gut Wall algebraic sum of all excitatory and inhibitory impulses Stimulus Response CNS *pp.199-202 - sympathetic connection to the CNS is through a sympathetic interneuron - release of NE on badrenergic receptors CNS GIT ACh Parasympathetic (preganglionic) - normally there is input from the CNS and autonomic system - there is no synapse between the CNS along the parasympathetic preganglionic fiber - the first synapse is with an enteric interneuron (can be excitatory or inhibitory) - they release Ach acting on nicotinic receptors NA ACh ENS Sympathetic (postganglionic) Autonomic Innervation of GIT AUTONOMIC INNERVATION OF GUT WALL - parasympathetic innervation begins in the medulla and pelvis and information travels along the vagus nerve - there is no synaptic interruption of the parasympathetic system - the sympathetic innervation begins in the spinal cord - lumbar and thoracic regions - there is synaptic interruption before forming synapses with the ENS - the gut provides information to the brain that is integrated centrally --> regulation of the level of activity in the enteric neurons - there is sensory input to the medulla and spinal cord - this results in parasympathetic and/or sympathetic activity to enteric interneurons (excitatory or inhibitory) - when you stimulate an excitatory enteric neuron there is increased activity - when you stimulate an inhibitory enteric neuron there is increased inhibition - inhibiting an inhibitory enteric neuron results in increased activity Secretory cell The ANS modulates the ENS The parasympathetic reaches the wall of the GIT as preganglionic fibres, synapsing (via nicotinic ACh receptors) with enteric neurons (both excitatory and inhibitory) exerting an excitatory effect. The sympathetic reaches the wall of the GIT as postganglionic fibres, synapsing (via NA receptors) with enetric neurons (both excitatory and inhibitory) exerting an inhibitory effect. The sympathetic also innervates smooth muscle in blood vessels in the wall, causing vasoconstriction. Sensory neurons also exist allowing for “long reflexes”. Emotional States integration of sensory input - if you stimulate at one point, because of the integration and wide distribution of the autonomic nervous system the distal ends of the digestive tract can be regulated - amplification of the sensory input Sight, smell, taste of food sensory fibers going from the gut to the CNS CENTRAL NERVOUS SYSTEM ps LONG REFLEXES s Efferent Autonomic modify, modulate the neurons the enteric innervationlevel of activity of - DO NOT regulate smooth muscle directly Afferent neurons G U T W A L L Chemoreceptors, osmoreceptors, mechanoreceptors Stimulus Nerve plexus SHORT REFLEXES Smooth Muscle or Gland Response ANS MODULATES ACTIVITY OF ENS ALLOWS FOR INTEGRATED ACTIVITY OVER LONGER DISTANCES ALONG GUT LONG, EXTRINSIC REFLEXES In general, PS – EXCITATORY (may also excite inhibitory neurons) S - INHIBITORY (may also inhibit inhibitory neurons) pp.589-590 HORMONAL REGULATION OF GUT ACTIVITY DES = DIFFUSE ENDOCRINE SYSTEM (scattered in mucosa) - individual cells, they do not collect together into an organ (such as in the thyroid) - cells are scattered out throughout the intestine and GI tract largest, most diversified endocrine system in the body it can operate in a variety of ways - over 20-30 substances are released in many different ways Different modes of regulation AUTOCRINE PARACRINE diffusion of hormone through the ISF ENDOCRINE diffusion of hormone through the vascular system capillary ENDOCRINE CELL GUT REGULATORY PEPTIDES - there are many ways of increasing or decreasing the activity of the intestinal tract 1. Released from mucosa into portal blood - all substances released are peptides, no steroid hormones liver systemic circulation are released 2. Have multiple targets intestine, gall bladder, pancreas - the substances are released from the mucosa into the portal blood, the blood flow from the gut to the liver - once they have gone through the liver, they enter the systemic circulation (they can be modified in the liver) - they are then transported to muscular and secretory elements the rest of the body to multiple targets excitatory inhibitory 3. Interact with one another and with neurotransmitters that are released locally at the level of the cell a) synergistically b) antagonistically GUT PEPTIDES A number of peptide agents are released from endocrine cells in the mucosa of the stomach and the small intestine by nervous, chemical, and mechanical stimulation, coincident with the intake of food. Released into the portal circulation, the gut peptides pass through the liver to the heart, and back to the digestive system to regulate its movements and secretion SUMMARY OF GIT REGULATION 1. Short enteric (intramural) reflexes the main control of the GI tract, merely modified by long reflexes and hormonal activity 2. Long extrinsic (ANS) reflexes modify short enteric reflexes, sympathetic and parasympathetic components 3. Hormonal Factors interact with neural regulation (#2 and #3 modulate effects of #1) GIT STRUCTURE, FUNCTIONS, REGULATION 3 Activities: 1. MOTILITY (muscular activity) Propulsion & physical breakdown Chemical Breakdown 2. SECRETION (glandular activity) 3. ABSORPTION - Transfer to circulation Pp 581 Longitudinal fibres Circular fibres narrow the lumen shorten the length of the tract striated LUMEN S M O O T H striated SEROSA MUSCULARIS EXTERNA basic muscular layer - 2 fibrous layers most of the muscular tube is smooth muscle, excluding the pharynx, larynx, uppwe 1/3 of the esophagus and the anal sphincter PROPULSION (FLOW) IN THE GIT Gradients of pressure Variations in resistance Coordinated contractions Normally, of muscular elements in segmentation - standing rings ofat little/no resistance contraction that are established - normally sphincters open in the different points along the tube arrival of a meal wall of GIT followed by relaxation and perastalsis - propagated wave of contraction that moves over the wall of the organ causing the narrowing of the lumen - causes the contents to move in the aboral direction, mainly responsible for propulsion contraction of the adjacent region of the tube - important in essential mixing activity, also responsible for a certain amount of propulsion - they do not offer any resistance - in the absence of a meal moving in the GI tract they are closed Normally, flow is slow, aboral and meets little/no resistance increased resistance of sphincters and the GI tract are manifestations of disease PHASES OF DEGLUTITION (swallowing) Pp.590-593 ORAL - three phases to swallowing correspond to the transfer of food through the oral cavity, pharyx and esophogus and into the stomach - the first propulsive activity of the GI tract PHARYNGEAL ESOPHAGEAL DEGLUTITION (Swallowing) is accomplished through a complex series of highly coordinated muscular movements aimed at building up pressure, temporarily sealing off of compartments to prevent dissipation of pressure, and decreasing resistance. ORAL PHASE – transport from anterior mouth to pharynx VOLUNTARY CONTROL - food is ingested into the mouth and is moved to the tip of the tongue - the food begins to move to the back of the mouth by elevation of the tip of the togue and depression of the back of the tongue - the food is thrusted into the pharynx by elevation of the middle part of the tongue - the ability to initiate swallowing in under oral control ORAL PHASE – transport of bolus (masticated, insalivated mass of food) from anterior to posterior portion of mouth. This involves a series of reflexes coordinated in DEGLUTITION CENTRE in medulla oblongata CORTICAL vs MEDULLARY CENTRES “Voluntary” facilitates the involuntary reflexes - makes them more smoothly integrated swallowing centers Deglutition Centre “Involuntary” ORAL PHASE CORTEX 1. ABILITY TO INITIATE: VOLUNTARY 2. COORDINATED MOVEMENTS: REFLEX (INVOLUNTARY) the actual movements that allow for the transport of the food from the anterior to the posterior regions of the oral cavity are involuntary MEDULLA PHARYNGEAL PHASE - the pharyx is the site where the respiratory and digestive tracts cross - the first thing that must happen during swallowing, the two tracts must be separated - the bolus enters the pharyx it initiates a series of protective movements that closes the openings back to the nose and to the trachea - only then can it enter the esophagus PHARYNGEAL PHASE INVOLUNTARY 1. - the bolus begins to pass downward and at the same time the vocal cords come together to seal the glottis and the whole larynx moves upward and forward to fit under the tongue --> main way to protect the respiratory tract - the epiglottis flips down to cover the lower respiratory tract --> secondary to the upward movement of the vocal cords to fit beneath the larynx - the upper esophageal tract relaxes (to decrease the resistance to flow) and the pharyx muscles contract (to generate a pressure difference)as the bolus enters into the esophagus - these involuntary contractions and relaxations are accompanied by deglutition apnea - inhibition of respiration Passages into nose, mouth, and trachea are blocked Apnea relaxes 2. 3. UES 4. Pharynx muscles contract PHARYNGEAL PHASE Under involuntary control, consists of a) a series of protective reflexes, initiated by stimulation of afferent fibres in the pharynx, organized in Deglutition Centre, closing off nasal, oral, and laryngeal cavities, preventing misdirection of the bolus. Simultaneously, respiration is briefly inhibited. b) transfer to esophagus, as pharyngeal muscles contract and Upper Esophageal Sphincter relaxes. DEGLUTITION REFLEXES afferent Pharyngeal Receptors DEGLUTITION CENTRE efferent “protective reactions” relax UES contract pharyngeal constrictor muscles “deglutition apnea” Vagus UES - striated muscle - in order to contract it needs to receive innervation - at rest in the absence of swallowing, the UES receives constant innervation from the CNS mediated by the vagus - releases Ach that acts on nicotinic receptors - on swallowing there is an inhibition of the vagally sent impulses - the muscle no longer receives regulation --> they relax ACh(N) CLOSURE – impulses originate in CNS, mediated by vagus, releasing ACh , causing muscle contraction RELAXATION – cessation of impulses, results in muscle relaxation PHARYNGEAL PHASE 1. Involuntary 2. Rapid 3. “Stereotyped” 4. Temporospatial Coordination - there are about 25 different muscles that must contract with the appropriate amount of strength at the correct times - it is one of the most vulnerable areas in neuromuscular disease - aspiration pneumonia - elderly people aspirate bacterial particles ESOPHAGEAL PHASE - main function is propulsion - transfer of the bolus from the UES to the LES - there is no absorption in the esophagus - the sole function is transport UES Body of esophagus lies within thoracic cavity - the pressure in the thoracic cavity is negative - the body of the esophagus lies in a subatmospheric region - the pressure in the pharynx is atmospheric - if there was no esophageal sphincters we would constantly be aspirating air each time you take a breath --> the UES keeps the top of the esophagus tightly closed - in the absence of swallowing, no air moves into the esophagus - if there was no LES we would constantly be refluxing the stomach contents into the lower esophagus - the esophagus does not have a mechanism to protect itself from stomach acid LES p h a r y n x UPPER GIT PRESSURES Intragastric (+ve) atmospheric pressure UES Body of Esophagus LES Intrathoracic (-ve) the vagus directly innervates the striated muscle - typical neuromuscular junction vagus UES Striated muscle vagus - in the smooth muscle region the vagus does not innervate the muscle, but it synapses with enteric interneurons which innervate the smooth muscle - autonomic innervation Smooth muscle LES ESOPHAGEAL FORCES 1. Gravity - you can swallow in the absence of gravity, if you stand on your head - gravity in the esophagus helps, but it is not the main mechanism 2. Peristalsis p.592 PERISTALSIS - a wave of contraction moving over the wall of the organ, narrowing the lumen and setting up a gradient of pressure favouring aboral movement Each time we swallow, a single PRIMARY PERISTALTIC WAVE is generated It takes 8-10 seconds to be propagated the length of the esophagus Primary peristalsis is part of the deglutition reflexes stimulation of pharyngeal receptors give rise to primary peristalsis cannot distinguish between the innervation or regions --> coordinated contraction - activation of the striated portions of the esophagus through vagal-somatic fibers - muscle contracts sequentially, propelling food toward the aboral end of the esophagus - vagal autonomic fibers activate almost at the same time as vagal somatic signals - but there is progressive delay in the enteric neurons - causes a propagated contraction - if the vagi are cut high up in the neck there cannot be the generation of a primary peristaltic wave - if the cut is lower down in the thorax, a wave can be generated because the striated muscle will still be intiated - a few of the enteric neurons will be initiated - it is sufficient to relay between the enteric neurons such that the wave propagates to the end - we need the activation of the vagus to introduce the signal into the esophagus, but in the distal region there is sufficuent relay such that there is pre programmed innervation Note that although the musculature of the proximal third of the esophagus is striated, while that of the distal third is smooth, the peristaltic wave moves over the entire esophagus as a smoothly propagated contraction. In the striated portion, peristalsis results from the sequential firing of vagal motor neurons, activating progressively more distal regions of the musculature. In the smooth muscle region, once some of the enteric neurons have been activated, they are capable of relaying and activating other entering neurons (in an orderly fashion), evoking and propagating muscular contraction in the aboral direction, independently of the extrinsic nerves. Thus, the integrity of the enteric innervation is critical to the propagation of the peristaltic wave in the distal esophagus. PRIMARY PERISTALSIS VAGUS is essential for initiating peristalsis in proximal esophagus Continuation and propagation in distal esophagus requires intactness of ENS there can be many secondary peristaltic waves until the bolus is dislodged (compared to only 1 primary wave) SECONDARY PERISTALSIS – -initiated by local distension; -may be mediated by enteric reflexes short reflexes -or by long (vagal) reflexes. Local distension Several secondary peristaltic waves may be generated, until bolus has been displaced - sometimes a bolus is very large and sticky and it can become stuck - local distention created by the bolus will give rise to a number of secondary peristaltic waves (it is not stimulated by the pharyngeal receptors) vagus LES pH=7 Anatomically insignificant, functionally very important CLOSURE: MYOGENIC RELAXATION: NEUROGENIC Local release of NANC LES NANC - there is no evidence of a sphincter anatomically - there is no enlargement of the muscle - the aboral 4cm of the esophagus straddle the diaphragm - it is important functionally - it is so effective as a sphincter that it allows for a pH difference of 5 units - it remains tonically contracted at rest in the absence of any innervation - destroying the enteric innervation or cutting the nerves will do nothing - it will remain closed during relaxation - it is under myogenic control - opening requires the release of NANC by the enteric neurons which causes relaxation - relaxation is brought about by the vagus innervation of enteric interneurons V pH=2 Pharyngeal Receptors DEGLUTITION CENTRE Vagal somatic Skeletal Muscle (upper esophagus) Vagal autonomic Peristaltic wave ENS (lower esophagus) Smooth Muscle (lower esophagus) LES relax. LES – lowermost 4 cm of the esophagus, straddling the diaphragm. When swallowing is not occurring, the sphincter is in a state of tone, and its walls are in firm apposition. The tone is largely myogenic, but under neural and hormonal influences. Relaxation of the LES is reflex, initiated during swallowing and mediated by vagal efferent fibres releasing ACh, which activate inhibitory enteric neurons which release a NANC transmitter, causing muscle tone decrease. NORMAL - there is an increased resistance to flow when the intragastric pressure increases - main mechanism to prevent reflux - the pressure in the intraabdominal LES increases as well --> can cause reflux HIATUS HERNIA - physiological example: pregnancy, as the uterus grows and displaces the GIT Increases in intraabdominal pressure increase pressure equally on stomach and intraabdominal LES If LES is entirely displaced into thorax, intraabdominal pressure increases do NOT increase LES pressure Note: the LES has an intrathoracic segment (subject to –ve pressure) and an intraabdominal segment (subject to +ve pressure), and the pressures within these segments vary with phases of respiration. The presence of an intraabdominal segment of the LES assists the sphincter in maintaining an effective barrier between the stomach and esophagus: if the intraabdominal pressure is raised, the pressure of both the terminal segment and the intragastric contents is raised equally, so that there is no effective change in the gradient of pressure between stomach and esophagus. LES Characteristics *1. INTRINSIC PHYSIOLOGIC SPHINCTER 2. Assisted by presence of an INTRAABDOMINAL SEGMENT Incompetent LES - Sphincter fails to close “Heartburn” (PYROSIS): burning sensation, radiating upwards in the chest towards the neck, due to acid reflux into esophagus HORMONAL MODULATION OF LES?? - progesterone will lower the resting pressure of the LES - it is thought that in the last trimester of pregnancy the reason that women have such large heart burn, part of this has to do with the large concentrations of progesterone present - this causes partial relaxation of the LES and cardiac sphincter PROGESTERONE LES - some text books will say that one of the gut hormones plays a role in regulating the tone of the LES - this is not true - it is a hormone that increases acid secretion - in large, non physiological doses it will cause a slight tightening on the LES but it has no physiological effect like this ? NO! Gastrin PHASES OF DEGLUTITION (swallowing) Pp.590-593 ORAL PHARYNGEAL ESOPHAGEAL MOTOR FUNCTIONS OF THE STOMACH - the stomach is not a major organ of digestion - there is no absorption that takes place from the stomach - the main functions are the motor functions 1. Temporary Storage: 1–2L the empty stomach is a very small organ, but it can increase in size to accommodate a large meal 2. Physical Disruption and Mixing of Contents: Semi-liquid consistency = CHYME converts the bolus into chyme - mushy consistency 3. Propulsion into Duodenum: Regulated - highly regulated propulsion - this is necessary because in order for digestion and absorption to be efficient in the intestine, the stomach must act as an effective storach, releasing small amounts of chyme per unit of time - slow, small quantities released at a time Pp.597-598 Structure – Motor Function cardia fundus fundus mucosa Pyloric sphincter antrum pyloric mucosa corpus body mucosa takes place exclusively in the proximal region thin walled exclusively thick walled Intragastric pressure = ~5 mm Hg - the empty stomach is a very small organ, there is hardly any lumen, about 50mL - the intragastric pressure when the stomach is empty is the typical intraabdominal pressure, +5mmHg - with the intake of meal, there is an increase in intragastric volume - in spite of the increase in volume, there is little or no change in intragastric pressure - this phenomenon is known as receptive relaxation - restricted to the proximal stomach, it does not occur in the distal region - the receptive relaxation is part of the deglutition reflexes - way before the bolus falls into the stomach there is receptive relaxation - once the bolus enters into the stomach there is further receptive relaxation by stimulation of local enteric neurons, local distention, short reflex - local distention also gives rise to a long reflex, a vagal-vagal reflex - the afferent and efferent regions of the reflex are mediated by the vagus - the vagal activation of the receptive relaxations is extremely important - the local distention reflex is much more insignificant - if you cut the vagus proximal to the proximal region of the stomach receptive relaxation is limited, you can no longer eat a large meal If the vagi to the proximal stomach are cut, receptive relaxation is limited, resulting in great increase in intragastric pressure. RECEPTIVE RELAXATION – is the ability of the stomach to accommodate a large meal without significant increase in intragastric pressure. It is restricted to the proximal part of the stomach. It is due largely to a vagally mediated reflex, initiated by swallowing, and resulting in the inhibition of muscle tone, and the consequent increase in intragastric volume. The transmitter released by the inhibitory enteric neurons activated by the vagus is NANC. The local distension created by the entering meal sets up local (enteric) and long (vago-vagal) reflexes which sustain the receptive relaxation. - in response to the intake of a meal there is a wave of suitable mechanisms that take place stimulation of pharyngeal receptors gastric phase PERISTALSIS – main form of contractile activity in distal stomach - the main activity in the distal stomach is peristalsis - there is no peristalsis in the proximal stomach - the pyloric sphincter is an integral part of the antral region of the stomach GASTROINTESTINAL PERISTALSIS – propagated contraction results from a series of local reflexes in response to local distension - it is similar to secondary esophageal peristalsis - initiated by local distention and involve a series of local reflexes --> propagated contraction AMPLITUDE how vigorous the contraction is depends on the stimulus - the greater the degree of distention, the greater the amplitude of contraction, within physiological boundaries MAGNITUDE OF STIMULUS (and interaction of neural and hormonal factors) FREQUENCY Direction Velocity ELECTRICAL CHARACTERISTICS OF SMOOTH MUSCLE different from the muscles in the proximal stomach Pp. 316 and 598 - put electrodes and measure the potential different across the membrane in the muscles in the proximal stomach, there will be a constant potential - if you measure the potential in the distal muscle cells, you will measure a resting potential that undergoes waves of depolarization that occur at regular intervals - the waves of depolarization are known as slow waves/BER/ECA - each cell/smooth muscle fibre of the distal stomach experience BER - each cell along the circumference will have the exact same rhythm and the waves of depolarization are synchronous - if you measure the potential along the long axis of the stomach, at every point there is a BER but the signal appears to migrate along the longitudinal axis - the BER is present all the time and it is always detectable - it is not always accompanied by contraction however - occasionally, a second electrical signal appears as a series of spikes - the ERA - it appears only at the peak of electrical depolarization and never between depolarizations - it moves synchronously along the circumference and migrates along the longitudinal axis - the second electrical signal is associated with a contraction - there is a definite 1:1 relationship between contractions and the appearance of the second electrical signal - the amplitude of the contraction is related to how many spikes there are in each spurt a BER is present, but no contraction Gastrointestinal smooth muscle cells show a resting membrane potential of ~60 mV (outside +ve). This “resting” potential is unstable, showing rhythmic depolarizations of 10-15 mV (at regular intervals, with uniform time course) which are propagated to adjacent cells. These spontaneous waves are the BER (basic electrical rhythm) or ECA (electrical control activity), and are independent of innervation. The BER is present continuously; occasionally, spike potentials occur at the peak of depolarization, and when they do, they are initiative of a contraction, which also spreads to adjacent cells. These spikes constitute the ERA (electrical response activity). ECA (BER) - constantly present – NOT initiative of contractions it is there all the time - propagated from cell to cell - f constant for a given region - detectable in both longitudinal and circular muscle - ORIGIN ????? (non-neuronal) ERA (“Spikes”) - intermittent - non-muscular and non-neuronal - it - phase-locked to BER (ECA) occurs in specialized cells - they cannot occur between the waves of BER - they must occur at ACh the peak of depolarization - stimulus Stretch ++ dependent - Ca - in longitudinal and circular fibres rom muscle - cell to cell propagation - MYOGENIC fmuscle cell cell to # spikes/burst magnitude of stimulus - associated with Spikes (ERA) CONTRACTIONS amplitude of contractions # spikes/burst - MAXIMAL f of contractions is LIMITED by f of BER (ECA) γ γ CONTRACTILE ACTIVITY Frequency – determined by f of BER (ECA) Propagation – though built in the ability of sm. muscle to propagate electrical signal from cell to cell, peristaltic contraction requires integrity of ENS - the ability to convey the signal from one muscle cell to another is dependent on the ENS - it integrates the activity of the propagation - the vagus and sympathetic activity (CNS) is not needed for peristaltic activity - cutting out the ENS will stop peristalsis Amplitude – determined by magnitude of stimulus (stretch, ACh) In the stomach, waves of depolarization begin in pacemaker cells in the musculature in the upper corpus, and spread towards the pylorus, with a frequency of 3/min, and at a velocity which increases from 1 cm/sec in the corpus to 3-4 cm/sec in the antrum. Spike potentials which are initiative of contractions occur only intermittently, though always with a fixed phase relationship to the BER (ECA). Consequently, when gastric contractions occur, they do so at intervals of one every 20 secs, or some multiple thereof. The effect of the higher conduction velocity in the antrum is that when a wave of contraction is set up, the whole terminal antrum contracts synchronously, and the event is termed ANTRAL SYSTOLE. contraction cannot exceed the BER - initially the contraction is weak and slow moving - as it moves towards the pyloric sphincter the band of contraction widens, the indentation is much great and the contraction becomes progressively stronger and more rapid until the contraction moves over the pyloric sphincter - the antral region and the pyloric sphincter contract simultaneously - antral systole - it is an enlargement of the circular muscle, but it is functionally insignificant because it remains open at rest - it is a very narrow diameter - in the absence of peristaltic activity there is little movement of chyme into the duodenum due to the absence of a large pressure gradient across the sphincter - as food contents are pushed towards the sphincter, particles that are very small can move through into the duodenum - it acts as a filter - food particles must be small enough to move across the sphincter RR= Receptive Relaxation - the emptying of liquid is dependent of a pressure gradient between the stomach and the duodenum - liquid can empty in the absence of peristalsis, the pyloric sphincter is always open - normally the gradient is not very large (because of receptive relaxation) - since the pressure difference is very small, liquid will move across the sphincter very slow - if you cut the vagus, you will not have RR and the pressure gradient will rise dramatically - this will cause a rapid increase in the amount of liquid that moves across the pyloric sphincter - if you cut the afferent nerves to the distal portion of the stomach, there will not be a large influence on the pressure difference across the pyloric sphincter - it is not peristalsis that brings about the emptying of liquid as much as 25mmHg higher - emptying of solids takes place in two stages - food is stored in the fungal region of the stomach - transfer to the distal stomach - food is subjected to peristaltic contractions - the distal regions behaves as a pump - every time the wave moves over the distal stomach some chyme is pumped into the duodenum - retropulsion - mixing and physical breakdown of the food which is too large to fit through the pyloric sphincter - the diameter of the sphincter is very small and only the smallest particles and liquid can fit through it PHYSICAL DISRUPTION and MIXING of MEAL This reduces meal to semi-liquid consistency of CHYME. Mixing is achieved as a result of the strong antral systole and the early closure of the pyloric sphincter: as the wave of contraction passes over the antrum, some of the chyme is discharged into the duodenum, but most of it is squirted back into the corpus at high velocity. This “retropulsive” turbulent flow results in effective mixing and physical disruption into a suspension of particles < I mm in diameter GASTRIC EMPTYING of Solids 1. FUNDIC (proximal stomach) RESERVOIR 2. ANTRAL (distal stomach) PUMP 3/min f x stroke volume fluidity of chyme determined by 2 key factors: there can be no more than 3 peristaltic waves per minute amplitude of contraction mainly determines the varying rate of gastric emptying - the size of the particles of food - only particles less than 1-2 mmHg can fit through the sphincter - does not give variation in output - in order to have a contraction there must be spikes superimposed on the BER - the number of spikes in each burst depend on the magtnitude of the stimulus (stretching the muscle, or the local release of Ach) - gastric peristalsis is determined by the stretch of the muscle (mostly) and enteric innervation - sensory fibers innervating through interneurons that release Ach - much more important are vagal reflexes - the vagus innervates the distal region - vagal-vagal impulses - vagal tone is constantly sending impulses to increase the strength of contraction - cutting the vagal innervation to the distal stomach, emptying of the food becomes much more sluggish, slow, less frequent - there is also the possibility of sympathetic reflexes that can be disturbed (they can stimulate inhibitory or excitatory interneurons) - reflexes involving the enteric nervous system bring about inhibition of gastric peristalsis - vagal-vagal impulses and and sympathetic activation of inhibition enteric interneurons - the final result is inhibition of antral peristalsis - all these reflexes are known as the enterogastric regflex - originates within the duodenum - much of the regulation of gastric emptying originates in the proximal duodenum - there is little or no digestion/ absorption in the stomach - the stomach is only a storage organ which allows for the meal to be stored temporarily before releasing small quantities into the duodenum such that it can be absorbed effectively - sensors are necessary for detecting the physical and chemical characteristics of the chyme as it enters the duodenum and send this information to the stomach - if too much chyme is released at once, there will be distention of the duodenum - the chyme will become acidified the small intestine must neutralize the chyme rapidly - the duodenum will signal the stomach if the chyme is too acidic - if the chyme entering the intestine is very hyper/hypotonic a signal will also be sent - it takes longer to digest and absorb fats than proteins and carbs - the amplitude of gastric peristalsis is controlled based on the type of meal - give rise to a release of hormones from the duodenum - all peptides do not go directly into the systemic circulation - they enter the portal circulation before returning to the heart and are pumped by the heart through the systemic circulation to the stomach and gastric circulation released form the duodenum and act on the distal stomach to decrease the amplitude of gastral contraction P 597 VOMITING -NOT the result of “antiperistaltic” waves! Pp.606-608 - relatively passive upper gastrointestinal tract - there is absolutely no contraction Increase in intraabdomi nal pressure the contents of the stomach travel to the area of lowest pressure, upwards (the upper GIT is relaxed) ++ Vomiting is entirely reflex; the Diaphragm reflex activity is organized in medullary Vomiting Centre - involves a number of phases - widespread autonomic discharge - autonomic innervation is activated such that there is an imbalance of the sympathetic and parasympathetic nervous systems - salivation, sweating, dilation of pupils, irregularities of heart, irregular breathing, nausea - there is retching, irregular uncoordinated contractions of the respiratory muscles - emesis - relaxation of the upper GIT and spasms of the antrum and then the fully coordinated contraction of the diaphragm and abdominals - chemoreceptor trigger zone = CTZ lies outside the blood brain barrier, distinct from the vomiting center - stimulated by substances that cannot act on the vomiting center because of the blood brain barrier - will send impulses to the vomiting center, activating it --> full efferent output - if the CTZ is not in tact, you can no longer vomit in response to circulating emetic agents while the vomiting center can still respond to other stimulants Vomiting involves three stages: (i) Nausea – a psychic experience (ii) Retching – abrupt, uncoordinated respiratory movements with glottis closed (iii) Emesis – actual expulsion of contents of upper GIT: individual takes deep breath, closes glottis, contracts abdominal muscles, exerting pressure on gastric contents. Emesis is completed with the reversal of thoracic pressures from –ve to +ve, as the diaphragm is displaced upwards, forcing esophageal contents to be expelled through the mouth. UPPER SMALL INTESTINE 1. NEUTRALIZATION 2. OSMOTIC EQUILIBRATION 3. DIGESTION 4. ABSORPTION Pp 603-604 MOTOR ACTIVITIES OF SMALL INTESTINE 1. EFFECTIVE MIXING 2. SLOW PROPULSION - must be slow enough for all these changes to take place - mix the chyme with the secretions that are released into the small intestine - osmotic equilibration, neutralization etc. 2-6 hours INTESTINAL CONTRACTIONS – governed by electrical characteristics of sm. muscle Frequency – governed by BER (ECA) ERA (spikes) – phase-locked to BER determines the maximum rate of contraction Amplitude of contraction – related to the number of spikes/burst of ERA (spikes) the amount of spikes on the BER are related to the strength of contraction and in turn to enteric innervation and release of Ach and stretching of the muscle INTESTINAL BER (ECA) Intrinsic f of different cells is very different – it declines systematically from proximal to distal intestine maximum number of contractions in the duodenum, 12/min - whereas in the stomach there is very good coupling of adjacent cells such that the pacemaker cells could drive the mucle cells to have the same frequency - this is not the case of the small intestine - they act as a series of cells that all have different intrinsic frequencies such that it cannot be driven by the same pacemaker cells 8/min Mechanism regulating intestinal motility: the BER (ECA) generated by the muscle fibres in the small intestine shows an aborally declining frequency gradient, with the highest frequency (12/min) in the duodenum and the lowest (8/min) in the terminal ileum. This gradient is determined by a series of pacemaker regions along the intestine, each with a slightly lower frequency than the preceding one. The distribution of the BER in time and space along the intestine establishes the distribution of spikes (ERA) and consequent contractions; thus, the proximal portions of the intestine exhibit more activity than the distal ones. The maximal contractile activity in the small intestine cannot exceed the BER frequency of that gut segment. PROXIMAL S.I. vs DISTAL S.I. 1. f of BER is greater 2. Excitability of sm.m. is greater 3.Thickness of sm.m. is greater less distinction in the proximal region to generate a strong contraction than in the distal there will be more vigorous contraction in the proximal versus the distal Therefore, both frequency and amplitude of contractions is greater in proximal S.I. Most common type of contractile activity: Standing rings of contraction - SEGMENTATION - effective mixing movement - pushes things back and forth over the same region of the intestine - most common type of contraction in the small intestine after the ingestion of a meal - digestive and absorptive purposes - net slow propulsive activity 1. Myogenic response to physiological distension 2. ENS organizes over longer regions of the gut 3. ANS (parasymp increases, symp decreases), and hormones modulate this is not required however FUNCTION MIXING - the contractile activity of the proximal SI is more frequent and more vigorous --> net movement in the net aboral direction, net gradient of pressure SLOW PROPULSION* Propagated wave of contraction - PERISTALSIS - propagated wave of contraction - in the SI it is not very frequent there are not rapid rushes of contents as a result of preistaltic activity in a normal individual In the Intestine INFREQUENT, IRREGULAR WEAK, SHALLOW, TRAVELS FOR SHORT DISTANCES ONLY (a few centimeters) INTESTINAL PERISTALSIS A SERIES OF LOCAL REFLEXES INVOLVES INTERACTION OF LONGITUDINAL (segmentation just AND CIRCULAR MUSCLE requires the circular muscle) Maximum f cannot exceed f of BER (ECA) at that particular region of the intestine INTEGRITY OF ENS required MODULATED BY ANS AND HORMONES The “Law of the Intestine” Pp 204-205 - digestion and absorption is completed by the time the chyme reaches the ilealcaecal valve - food will not be digested and absorbed in the colon COLON MOTILITY similar to S.I. but slower, more sluggish, irregular Digestion and - 1500mL of a very liquid Absorption of chyme enters the colon per day and only 200mL Nutrients is exits the anus - the rest of the fluid, 1500 mL water and ions, are completed in S.I. absorbed by the colon - this job is started by Some H2O and the small intestine and completed by the colon ions still to be absorbed 200 mL FUNCTIONS: MIXING - promotes Absorption of Water and Ions PROPULSION – Slow (50 – 60h) STORAGE until elimination MOTOR ACTIVITY MIXING PROPULSION & STORAGE - same mechanisms as the small intestines: segmentation and peristalsis - much more slow, sluggish and irregular - this has to do with the frequency on the BER, it is very irregular (compared to the constant f in the stomach) - the f is very high in the rectum - it is higher in the proximal than the distal region - the contractile activity as a result is irregular throughout - much of the segmenting takes place in the more proximal regions - propulsion and storage more take place in the distal regions SEGMENTATION and PERISTALSIS governed by irregular BER - 2 to 3 times a day there is increased activity at the terminal ileum and relaxation of the ileocaecal valve along with increased peristalsis in the distal ileum - as the stomach gets distended by a new meal a number of reflexes known collectively as the gastroileal reflex are initiated - this involves the distention of the stomach bringing about by both enteric and autonomic nerves the increased activity of the distal ileum and a relaxation of the ileo-caecal sphincter to reduce resistance to flow resulting in the release of AFTER A MEAL GASTROILEAL REFLEX - simultaneously this brings about the gasrocolic reflex causing increased peristalsis in the distal colon pushing contents into the rectum and relaxation of the anal sphincter - the ileocolic reflex helps in the emptying of the small intestine into the colon and the emptying of the colon into the external environment ILEOCOLIC REFLEX GASTRO COLIC REFLEX p.604 INTERDIGESTIVE PERIOD GI Motility organized into intense pattern of cyclic myoelectric (motor) activity a) recurring at regular intervals (~90 minutes) b) moving sequentially over distal stomach and small intestine up to distal ileum (~2-10 cm/minute). it does not affect the colon - characteristic cyclic motor pattern - the GI tract does not just sit there MMC (Migrating Myoelectric (Motor) Complex) S.I. BER still is there frequency is equal to the frequency of the BER (e.g. duodenum 12/min) - this pattern migrates sequentially along the small intestine - at every point the MMC will appear 90 minutes later - it takes 90 minutes for the MMC to migrate from the distal stomach to the distal small intestine the MMC stops on ingestion of a meal and it will not resume until many hours after the meal MMC - restricted to distal stomach and S.I. - INITIATION - can CNS? ANS? not beremove CNS/ANS innervation and MMC will interrupted - gut peptides are not exactly understood GUT PEPTIDES? ENS – periodic activation of pattern-generating circuitry * - PROPAGATION via * ENS with modulation via ANS and Gut Peptides - INTERRUPTION Intake of a new meal MMC FUNCTIONS • “HOUSEKEEPING” - cleaning - the contents of the distal stomach and small intestine are never totally emptied - debris are left by non digestible substances, secretions, cells - the S.I. is usually free of bacteria but sometimes bacteria can reflux from the colon - the MMC is thought to sweep away the contents that have accumulated during the interdigestive period - prevents the accumulation of material • GASTRIC EMPTYING OF LARGE NON-DIGESTIBLE PARTICLES - larger particles are not emptied with the meal but rather during the interdigestive period - the pyloric sphincter has a narrow diameter - larger particles cannot escape during antral systole - during the interdigestive period there are movements that sweep contents along - the sphincter is not contracted during the interdigestive period Pp.127-129 SECRETION - can fall into two major categories: endocrine and exocrine - the lumen of the digestive tract is continuous with the external environment - so, any secretion released into the lumen of the gut is in the exocrine system - endocrine secretion give rise to gut peptides that have a regulating effect and are released into the internal environment EXOCRINE GLAND SECRETION ENDOCRINE EXTERNAL ENVIRONMENT INTERNAL ENVIRONMENT DIGESTION Chemical breakup to progressively smaller molecules results from the secretory activity of a large number of exocrine glands found within and in association with the GIT, releasing their products into the lumen of the digestive tract. Secretion is an active, energy dependent and blood flow dependent process, resulting in the release of a fluid containing ions and a variety of enzymes. 3 Types of enzymes: AMYLASES - there is a sequence of interdependent steps - large molecules are broken down into smaller ones which are broken down into even smaller ones - this breakdown occurs to the molecular level until absorption can take place - enzymes are proteins are are necessary for the breakdown of food materials - there is a duplication of enzyme activity, enzymes are secreted at different parts along the tract and not only in one place - it may be a protective mechanisms - enzymes require very specific pH and ion compositions to function properly act on carbohydrates act of proteins PROTEASES LIPASES act on lipids PATTERN of REGULATION a) Nervous (ANS) b) Hormonal (Gut Peptides) - glands can be stimulated to secrete by nervous system (autonomic) or in response to gut peptides - at the level of the head, regulation is entirely nervous - further down the GI tract the less important neural regulation becomes and more important hormonal regulation becomes - at the level of the stomach there is both hormonal and nervous regulation Pp591 P 579-580 - three major salivary glands - parotid gland releases a water serous fluid containing amylase - the sublingual gland produces a thick viscous mucus - the submandibular gland is a mixed gland that produces both MAJOR SALIVARY GLANDS SEROUS MIXED MUCOUS SALIVA VOLUME: 0.5 – 1.5 L/d IONS: Na+, K+, Cl-, HCO3pH: 6.5 – 7.0 STARCH Polysaccharides MUCIN LIPASE ? LYSOZYME PTYALIN pH ~7 MALTOSE Disaccharides HYPOTONIC - all different glands in the GIT secrete small amounts of fluid in the interdigestive period but most of the secretions take place on ingestion of a meal - in saliva all key ions of plasma are present but their concentrations are much smaller - it is hypotonic - saliva is the only hypotonic secretion (all others are isotonic) - ptyalin, or salivary amylase breaks down polysaccharides to the level of disaccharides but no further - mucin lubricates the bolus (it is a thick mucus liquid) - forget about lipase - lysozyme has an antibacterial activity REGULATION: ANS SYMPATHETIC PARASYMPATHETIC [Blocked by ACh (M) ATROPINE] SECRETION VASODILATATION ? VASOCONSTRICTION REGULATION OF SALIVARY SECRETION (simple and conditioned reflexes) eyes, nose, etc. “HIGHER CENTRES” Sensory receptors in mouth - stimulation of chemoreceptors, mechanoreceptors AFFERENT condition reflexes stimulation from higher centers e.g. thinking about food Salivary glands EFFERENT via parasymp. supply “Salivary Centres” in Medulla P 579590 P. PHASES OF SECRETION • PSYCHIC • GUSTATORY CEPHALIC simple reflex arc as the food is put in your mouth = head in greek they are initiated at the level of the head, brain or mouth • (GASTRIC/INTESTINAL) - some reflexes will cause more saliva to be released when hot/spicy food is ingested for example Pp 582-586 Pp.591-597 MIXED GASTRIC JUICE 1.5 – 2 L/d Isotonic Fluid: pH 1-2 Pepsinogen protease - can collect from stomach - reflect secretory activity of different glandular cells located in the stomach Na,+, K+, Cl- , H+ high concentration of hydrogen ions Intrinsic factor Mucin - only secretion of the stomach that is essential to life - it is required for the absorption of vitamin B12 Surface epithelial cells secrete a mucous, alkaline fluid - there are a large number of tubular glands that dip below the surface of the stomach - the cellular composition of the tubes differ based on the location in the stomach - in the cardia and antral region the cellular elements are fairly uniform and secrete an alkaline, mucin rich - in the corpus and the fundus the tubular glands have a much more complex composition - parietal cells are responsible for secreting acid - chief cells release pepsinogen and musus neck cells release mucin CARDIAC and PYLORIC tubular glands secrete an alkaline, mucin-rich fluid GASTRIC GLANDS IN FUNDUS AND CORPUS Pp.593-597 HCl Pepsinogen inactive precursor to pepsin Mucin tubular glands in fundus and corpus STRUCTURE of PARIETAL CELL LUMEN Canaliculus - many mitochondria - characterized by intracellular canaliculus - channels that penetrate into the cell - they are open to the lumen - they communicate with the gastric lumen - require high metabolic rate, need lots of energy to produce isotonic gastric juice Maximum rate of secretion ∝ number of parietal cells three enzymes are important in the secretion of H+ - carbonic anhydrase - H+/K+ ATPase on the canalicular membrane - Na+/K+ ATPase in the basolateral membrane parietal cell - each will have many canaliculi - the larger the number of parietal cells, the more gastric juice is secreted - non-parietal cells release very small amounts of gastric juice capillary HCO3- Carbonic anhydrase lumen H+=4 x 10-5 mEq Na+/K+ ATPase HCl (isotonic) 150 mEq H+ H+/K+ ATPase 150 mEq ClCanalicular 4 million times higher hydrogen ion the membrane than in mustplasma - there be important active - Na+/K+ and carbonic anhydrase are not unique to the parietal cell, blocking H+ secretion from them would have other effects too - H+/K+ ATPase is unique to this location - PPI (proton pump inhibitors) can block H+ secretion - Nexium, Losec treatment of ulcers transport taking place - for every hydrogen ion secreted into the lumen there is a bicarbonate ion secreted into the capillary - maintains neutrality - a large amount of bicarbonate is secreted into the blood at the intake of a meal such that the venous outflow from the stomach becomes alkaline Postprandial (urinary) alkaline tide - hydrogen ion is pumped in exchange for K+ ion that is brought into the cell - carbonic acid in the cell neutralized the hydroxyl ion to produce water and bicarbonate - bicarbonate diffuses into the bloodstream in exchange for an chloride ion - chloride ion enters the lumen in a 1:1 ratio with H+ ions - K+ re-enters the cell in exchange for Na+ ions - the greater the number of H+ ions pumped, the greater the volume of water is produced - after a very large mean (of protein) the venous output becomes extremely alkaline Scheme for HCl Secretion a) Cl- entering the cell is actively transported across the canalicular membrane. b) H+ available from the dissociation of intracellular water, is also actively pumped into the canaliculi in exchange for K+ c) The secretion of H+ leaves an excess of OH- in the cell, resulting in an increase in intracellular pH. This causes more CO2 to diffuse in from the plasma (together with cellular metabolic CO2 ) combines with water in the presence of Carbonic Anhydrase to produce H2CO3. H2CO3 reacts with the excess OH- to yield H2O and HCO3-; the latter diffuses into the circulation, restoring the intracellular status quo, and giving rise to an increased alkalinity in the venous blood. d) Water moves into the canaliculi passively. PARIETAL CELL SECRETION – pure HCl fluid CONSTANT COMPOSITION, pH ~ 0.8 Independent of type, magnitude of stimulus the parietal cell cannot do anything else other than produce this type of fluid MIXED GASTRIC JUICE pH ~ 1-2 Modified by non-parietal alkaline gastric secretions non-parietal cells produce a neutral to alkaline fluid pH of mixed gastric juice depends on the # of parietal cells that are active the amount of HCl released is proportional to the number of parietal cells FUNCTIONS OF HCl 1. PRECIPITATES SOLUBLE PROTEINS - liquids leave the stomach quickly, but precipitation of the proteins means that they will stay in the stomach longer - precipitation will slow down the rate that they will enter the S.I and therefore digestion and absorption 2. DENATURES PROTEINS 3. ACTIVATES PEPSIN secreted as an inactive precursor that must be activated by acid and PROVIDES OPTIMAL pH for its activity - once a small amount of pepsin has been produced the reaction can proceed autocatalytically - most of the activation is as a result of pepsin acting on pepsinogen - pepsin is a general protease - works at an optimal pH at 2-3 - the amount of breakdown is limited, breaks down to intermediate polypeptides - most digestion takes place in the small intestine as a result of pancreatic enzymes INTRINSIC FACTOR in gastric juice The only secretion of the stomach essential to life - a glycoprotein - secreted by the parietal cells - required for the absorption in distal small intestine (ileum) of physiologically adequate with intrinsic factor in the amounts of dietary Vitamin B12 combinesand the complex travels stomach along the intestinal tract before it is absorbed in the distal ileum - Intrinsic Factor deficiency - cannot give vitamin B12 orally - must be administered intramuscularly or by IV Pernicious Anemia neurological anemia MUCIN - the entire lining of the stomach - it is secreted by most of the cells in the stomach: surface epithelial cells, cardiac and pyloric glands and the mucous neck cells Does it protect against damage by acid? - it plays a role, but it is not the most important role lumen of the stomach Gastric Mucosal Barrier (GMB ) (apical surfaces and tight junctions) CO2 + H2O MUCI-BICARB LAYER H+ pH ~2 Mucous Gel 1-2 mm of mucin pH ~7 HCO3- Mucin - the mucous layer is not impermeable to H+ - H+ can readily diffuse through - the mucous layer can adsorb the alkaline secretions produced by the non-parietal cells - the surface epithelial cells secrete an alkaline fluid, and the bicarbonate penetrates into the mucous layer - as the hydrogen ions diffuse through, they are neutralized - most of the H+ that diffuses into the mucus layer never reaches the surface epithelial cells - muci-bicarb layer = first line of defence - should the H+ diffuse through the mucus it will not enter the surface epithelial cells because the apical surface and tight junctions are relatively impermeable to H+ - this is not found in the intestine - this impermeability is the main defense of the stomach against H+ - gastric mucosal barrier (GMB) Surface epithelial cells line the stomach capillary GASTRIC MUCOSA – PROTECTION • MUCI-BICARB LAYER - the first line of defence • *GASTRIC MUCOSAL BARRIER (GMB) - the more important mechanism • RAPID CELL TURNOVER (“re-epitheliazation”) - millions of cells are replenished at a rate of millions per second Pp 595-598 ULCERS 1. Normal HCl output Weak barrier GMB is weakened (Aspirin & NSAIDs) (Helicobacter pylori) favour penetration by the acid 2. Normal Barrier Excessive HCl output main stimulant for acid production (e.g., Gastrin-producing tumors) primarily the duodenum is more susceptible to damage - at the level of the stomach there is both neural (vagus and sympathetic) and hormonal regulation (gastrin, histamine, SS) - enteric innervation innervates every singly secretory cells by releasing Ach on muscarinic receptors - there is also vagal activation of interneurons - the vagus releases Ach on nicotinic receptors on the enteric interneurons - whenever there is secretion there is also vasodilation - sympathetic innervation release NE inhibiting secretory activity - the cephalic phase (psychic and gustatory) is mediated via the vagus - vagotomy to stomach abolishes the cephalic phase - acid will still be released once the food enters the stomach without a preparatory phase - distention of the stomach gives rise to short, local interneural reflexes - results in the secretion of mucous - in addition, there are also long reflexes that are generated in which both the afferent and the efferent fibers are in the vagus - vagal-vagal reflex - primary release of gastric juices is due to hormonal activation - ingestion of food that is high in protein and placing them specifically in the antral region, parietal cells will secrete a large volume of gastric juice, even if the rest of the stomach was de-innervated - this means that the release had to be innervated by something in the blood - gastric is released by the antral region of the stomach - gastric juice released in response to gastric is particularly rich in acid GASTRIN is released in response to: a) SECRETAGOGUES (products of protein - largely small peptides digestion) -- can be single amino acids cells stimulate gastrin releasing b) Local enteric reflexes - enteric neurons stimulate gastrin producing cells c) Vagally-mediated reflexes - if the vagus can cause the release of gastrin, then during the cephalic phase even if you never swallow food the stomach will secrete acid and there is also increased gastrin in the circulation - gastrin is released by vagally mediated reflexes Gastrin release is “self-regulating” - when secretagogues enter into the antral region of the stomach they stimulate the release of gastrin which is pumped throughout the circulation before acting on parietal cells to release acid, activating pepsin by achieving optimal pH - this is a positive feedback mechanism, gastrin increases the release of more gastrin - built into the selfregulating system - when the pH in the antrum reaches below pH of 2, gastrin secretion is decreased Gastrin Parietal Cell G G Cell pH<2 SS Cell (-) Activates Pepsin HCl in antrum Secretagogues (protein products) Optimal pH PHYSIOLOGICAL ROLE OF GASTRIN a) HCl secretion b) Trophic effect - it promotes the integrity of the growth of the gastrointestinal mucosa - removing gastrin releasing cells, there is atrophy of the mucosal layer HISTAMINE??? Lots of Histamine in gastric mucosa Histamine administration elicits large volume of gastric juice with lots of HCl - it was speculated that the hormone in the antrum was histamine - injecting histamine into an individual, they will secrete lots of gastric juice with a low pH - it acts on the parietal cells - if you inhibit the histamine receptor you diminish, but not block completely, the responsiveness to Ach and Gastrin ACh HISTAMINE Gastrin - histamine is constantly released (there is always a background level of histamine release) - three important receptors in the parietal cell - stimulating one cell and slightly stimulating another will greatly increase in response of the cell to the first stimulant - the response of the cell to a maximal dose of Ach is increase by a sub threshold dose of histamine - there must be interaction of receptors X PARIETAL CELL blocking one receptor will influence the cell's response to stimulation of another receptor SEPARATE RECEPTORS: RECEPTOR INTERACTION hypothesis There is an interaction among the 3 receptors (Histamine, ACh, Gastrin). Blockade/Stimulation of one receptor, changes the properties of one or both of the other 2 receptors) PERMISSIVE HYPOTHESIS – Histamine is constantly released and presented to the Parietal Cells as a tonic background, sensitizing them to other stimuli. Blocking this tonic background by H2antagonists, inhibits acid secretion in response to ACh and Gastrin histamine receptor on the parietal cell H2 blockers are widely used to decrease HCl secretion - Pepcid and Tagadet diminish the receptiveness not only to histamine but also other stimulants - they do not completely block responsiveness to Ach or Gastrin but diminish their effect - they do not affect the receptors that for example are involved in asthma - gastrin like hormone is released from the duodenum that acts specifically on the parietal cell causing the secretion of more HCl in the gastric juice released into the portal circulation and eventually back to the stomach pumped by the heart INTESTINAL PHASE - Inhibitory - if the contents of the stomach are going to be stored for a long time, you do not want the chyme to be too acidic - it is logical that the same conditions that cause inhibition of peristalsis will also cause the inhibition of acid release - excessive distention, low pH, increased osmolarity and chemical composition - mediated by the enteric nervous system, vagal-vagal reflexes and the sympathetic nervous system - collectively known as the enterogastric reflex INTESTINAL PHASE - Inhibitory - same conditions in the duodenum will inhibit gastric secretion and motility **both motor and secretory activities of the stomach at any moment ion time reflect a balance between excitatory and inhibitory regulation Optimal secretory activity is the result of an interplay between neural and hormonal mechanisms. Gastric secretion at any moment in time reflects a balance between stimulatory and inhibitory influences. Review mediators of cephalic (vagus and vagallyreleased gastrin), gastric (local enteric reflexes, vago-vagal reflexes, gastrin release [and inhibition of gastrin release], and intestinal (excitatory, and inhibitory aspects via enterogastric reflexes and enterogastrone hormonal complex release) phases. Don’t forget to consider what the stimulants are in each case. PRE-INTESTINAL CHANGES 1. Reduced to semi-liquid consistency 2. Acidified o.p.? 3. Limited Digestion - 60% percent of dietary starches are broken down by salivary amylases (they are not needed though, pancreatic amylases can do the job just the same) - chyme - bolus is mixed with gastric juice - as a result of mixing with acidic gastric juices - osmolarity has not changed - there is no absorption from the stomach or loss/gain or water - a hypertonic meal entering the duodenum, water from the circulation will enter the lumen of the intestine to bring the meal to isotonicity (and same for hypotonic) - isotonicity is achieved in the duodenum Salivary amylase Some Polysaccharides Some Proteins Lipids Gastric pepsin Disaccharides Polypeptides Di-, monoglycerides, fatty acids UPPER INTESTINE NEUTRALIZATION - the intestine does not have a mucosal barrier - all secretions into the intestine are alkaline OSMOTIC EQUILIBRATION DIGESTION continues ABSORPTION begins - occurs specifically in the duodenum - everything that leaves the duodenum is isotonic - begins in the small intestine - as soon as food is broken down into the absorbable level, they are absorbed (monosaccharides for example) Pp 598-601 PANCREAS: Endocrine & Exocrine components - exocrine secretions are released into the lumen of the intestinal tract which IS the outer environment - thus they can be considered exocrine exocrine secretion - specialized duct cells release a large volume of juice with a very high alkalinity (rich in bicarbonate) - a small volume of juice is rich in enzymes PANCREATIC JUICE Volume: 0.5 – 1.5L/d Isotonic: ~300 mOsm Main Electrolytes: Na+, K+, Cl-, HCO3pH: 7.2 – 8.2 - the concentration of bicarbonate is higher than in plasma - it is alkaline - it is one of the alkaline secretions released into the duodenum ENZYMES: 3g% protein AMYLASES PROTEASES LIPASES - in ever 100mL of pancreatic juice there are 3 grams of protein - well over 90% of the protein is in the form of enzymes - the full compliment of digestive enzymes - very similar in its composition and function to salivary amylase - it too acts on polysaccharides to be broken down at an optimal pH of neutrality to disaccharides - disaccharides must be further broken down to be absorbed For absorption, disaccharides must be first converted to monosaccharides. PROTEASES intestinal enzyme - all proteases are released as proenzymes, inactive precursors - active proteases in the gland can destroy the gland itself (acute pancreatitis) - activation does not take place until the pancreatic juice enters the intestine - they are not active in the pancreas - trypsin also activates every one of the other pancreatic proteases: - trypsin itself can activate trypsinogen - positive feedback mechanism - there is a backup protective mechanism should any trypsin becomes spontaneously activated in the gland - the same cells that release trypsin also release trypsin inhibitor, which binds trypsin inactivating it and keeps it inactive until it is released into the intestine TRYPSIN INHIBITOR- inactivates trypsin Secretion of Trypsin Inhibitor It is important that the proteolytic enzymes of pancreatic juice not become activated until they have been secreted into the intestine, for the trypsin and other proteases would digest the pancreas itself. Fortunately, the same cells which secrete the proteases of the pancreas secrete simultaneously another substance called TRYPSIN INHIBITOR. This substance prevents activation of the trypsin, both inside the secretory cells and in the ducts of the pancreas. Since it is trypsin that activates the other pancreatic proteases, trypsin inhibitor prevents the subsequent activation of all these. pro-colipase Trypsin colipase Lipase Triglycerides pH~8 , Fatty Acids, DiMono-glycerides - lipase and amylase are secreted in an active form - lipase acts at an optimal pH in the alkaline range - it breaks down triglycerides into fatty - 2 groups of cofactors are needed for digestion - the first, colipase, allows the lipase to get a grip on the fat - the lipase requires a watery environment to work, but the fat is insoluble in water - colipase brings the lipase and the triglycerides together - it is secreted in pancreatic juice in an inactive form and is activated by trypsin in the intestine - the second are bile salts which are secreted by the liver - in the absence of lipase, colipase or bile salts fat digestion is inefficient Bile Salts LIVER Pp.601-602 LIVER & BILIARY SYSTEM LIVER BILE COMPOSITION Volume: 0.5 –1.0 L/d small amounts are secreted during interdigestive period and larger amounts after the intake of a meal ISOTONIC FLUID: Na+, K+, Cl-, HCO3pH: 7.8 – 8.2 SOLIDS ~3% no digestive enzymes helps together with pancreatic juice to neutralize gastric juice BILE ACIDS (SALTS) - billirubin - breakdown product of hemoglobin - give bile have nothing to BILE PIGMENTS digestion, its colour,excreted from thedo with they are body CHOLESTEROL PHOSPHOLIPIDS Bile secretion by the liver is continuous; it releases about 0.5 – 1.0 L/day. associated with the intake of meals Entrance into duodenum is intermittent, and the volume of bile entering it is <<<< 0.5 – 1.0 L/day. HOW COME???? - the liver secretes bile continuously - during the interdigestive period the sphincter of oddi is closed, providing a large resistance - the bile travels along the pathway of least resistance and into the gallbladder for storage - the solids are concentrated when they are in the stored in the gallbladder - the volume is decreased GALLBLADDER FUNCTIONS - cholecystectomy - you can still digest fat, but more dilute bile flows directly into the duodenum - sometimes the common bile duct dilates to accommodate the volume when the sphincter of oddi is closed - there is enough bile salt in the dilute bile from the liver to digest a sufficient amount of fat 1. CONCENTRATES SOLIDS Hepatic Bile 3% Gall Bladder Bile 10-20% 2. REDUCES pH Hepatic Bile 7.5 –8.0 Gall Bladder Bile 7.0-7.5 3. INCREASES VISCOSITY Remember: GB does not synthesize Bile Salts – it just stores and concentrates them BILE SALTS are synthesized in the liver from CHOLESTEROL. These surface-acting agents have the following properties: 1. They combine with fat-soluble substances to form water-soluble complexes 2. They reduce surface tension and stabilize emulsions 3. They assist in the transport and absorption of fat and fat-soluble Vitamins (A,D,E.K) Pp 584-585 BILE SALTS and MICELLE FORMATION - when the bile salts occur in small concentrations they remain dispersed in solution - in higher concentrations they form molecular aggregates that can be spherical or cylindrical - they provide a water soluble, polar surface on the outside and a non polar lipid solube surface on the inside - creates a shell that is water soluble and a core that is lipid soluble --> micelle - the micelle can remain in solution because the exposed shell is hydrophilic - non polar fats, vitamins and cholesterol can be hydrophilized when they are contact with the interior of a micelle - the fats can be transported into the intestinal cells where they are going to be absorbed Mixed Micelle Non-polar surface Polar surface A,D,E,K Bile Salt Pool: Daily synthesis: Daily release into intestine: 3.5 g 0.5 g 15 – 20 g How come??? - the body conserves bile salts very carefully ENTEROHEPATIC CIRCULATION - liver synthesizes the salts and releases them into the intestinal tract directly or from the gall bladder - very small portions escape into the colon (and even those are recycled later on) - 90% is actively transported from the intestine into the portal blood and back to the liver - the liver reabsorbs the bile salts and re-releases them into the intestinal tract BILE SALTS >90% actively reabsorbed in distal ileum 10% escape into colon, where they undergo colon ileum BACTERIAL MODIFICATION a certain proportion also gets reabsorbed ENTEROHEPATIC CIRCULATION BILE SALT FUNCTIONS 1. Intraportal – regulate volume of bile secreted by liver - regulate synthesis of new bile salts the liver will normally only synthesize the amount of bile salts lost in the feces 2. Intrahepatic – keep cholesterol in solution in the ductules of the liver - hepatocytes secrete bile salts into narrow channels/ductules 3. Intraintestinal (S.I.) 4. Intracolonic INTRAPORTAL ROLE OF BILE SALTS 1. Regulate hepatic bile flow - the more BS returned via portal blood, the larger the volume of bile secreted +ve feedback - if you return x grams of bile salt per day, the liver will secrete a given amount of bile - increasing x/2 grams of bile salt, the liver will secrete much less bile - the more bile salt returned, the more bile is secreted colon ileum - if the distal ileum is removed (where most of the bile salts are absorbed) the volume of bile secreted will decrease INTRAPORTAL ROLE OF BILE SALTS 2. Regulate the synthesis of NEW Bile Salts - the more BS are returned in Portal Blood, the smaller the amount of NEW BS being synthesized - high concentration of bile salts returned to the liver will inhibit the synthesis of new bile salts - the liver regulates the bile salt produced based on the amount of bile salt returned - what will happen to the bile salt synthesis if the ileum is removed - more bile salts will be synthesized because less will be returned colon ileum -ve feedback INTRAHEPATIC FUNCTIONS Keep cholesterol in solution. - cholesterol is insoluble in water - in bile. solubility of cholesterol is increase 2E06 - normally we do not have gall stones because the bile salts are solubilized inside micelles Phospholipids – if cholesterol precipitates out of solution, it may give rise to gallstones INTRAINTESTINAL FUNCTIONS 1. Act as detergents and help form stable - lumenal contents are largely emulsions watery - help the mixing movements, segmenting movements in the small intestine to break down the large drops of fat into smaller globules - increases the SA for the action of lipase and colipase to act upon 2. Assist in the transport from lumen into intestinal cell of fat and fat-soluble vitamins A,D,E,K. - fatty lipids diffuse into the cells because they are solubilized inside the hydrophobic pocket of a micelle INTRACOLONIC FUNCTIONS Inhibit Na+ transport and H2O absorption Excess BS in colon Diarrhea - normally this plays a minor role in maintaining feces as a semi-solid - some water is retained in to the distal colon as to maintain some fluidity to feces - if the concentration of bile salts in the colon, there will be a large amount of sodium retention in the colon and diarrhea will result - the liver releases bile continuously REGULATION OF BILE FLOW CHOLERETICS: agents which cause the liver to secrete a larger volume of bile e.g. bile salts in the portal blood CHOLAGOGUES – agents which cause an increase in the emptying of the G.B. relaxation of the sphincter of oddi and increase in pressure (contraction) in the gall bladder Law of Reciprocal Activity: CONTRACTION OF G.B. and RELAXATION OF SPHINCTER OF ODDI and vice versa PHASES OF SECRETION PSYCHIC CEPHALIC GUSTATORY GASTRIC in response to the intake of a mean INTESTINAL SUMMARY OF REGULATION OF BILE AND CCK and secretin also PANCREATIC JUICE inhibit gastric emptying and gastric secretion wants to slow things down until there is enough time to digest and absorb LIVER GB Contr /Sphincter Relax PANCREAS PANCREAS low vol/high High vol/low enzyme high pH enzyme high HCO3 +++ VAGUS mediates the cephalic phase + +++ -- GASTRIN vagal-vagal mediated reflexes + + + + CCK S.I in the presence of-from the upper fat (and products of protein digestion) +++ +++ -- SECRETIN low pH + -- -- +++ BILE SALTS +++ -- -- -- As a result of the secretory activity of salivary, gastric, pancreatic, hepatic secretions, amylase Polysaccharides Disaccharides Monosaccharides Amino acids, Di, tripeptides pepsin, trypsin Proteins Small Peptides chymotrypsin lipase, co-lipase Fats bile salts Mono, Diglycerides, FAs Entire intestinal mucosa is characterized by CRYPTS and VILLI a) COMPLETE DIGESTION b) ABSORPTION - produced by the intestinal cells themselves - they are very complex cells and it must be distinguished between the different types depending on their locations - crypt region dips below the midline - villi project into the intestinal lumen - there is a continuum between the crypts and villi but their cellular components are very different - the crypts lack digestive enzymes and do not perform any absorption at all but they release large volumes of fluid - the villi secrete the enzymes necessary for the final digestion and they absorb the final products FLUID SECRETION - crypts --> succus entericus - large volume - isotonic, but bicarbonate concentration is higher than in plasma - pH: 7.5 - 9 - no enzymes but rather just a large volume of alkaline fluid (villi do not secrete fluid) - crypt cells divide rapidly and migrate up the villi to replace cells at the tips of the villi, which are shed - crypt cells do not stay in to the crypt always, but differentiate and begin to migrate upwards, acquire the ability to synthesize enzymes, digest nutrients (and immediately absorb them) - when the cells read the tip, they are shed - CRYPT Cells lack digestive enzymes but secrete a large volume (3L/d) of alkaline fluid known as SUCCUS ENTERICUS - proliferative zone - cells rapidly divide and migrate up the villi - they mature, and become capable of synthesizing digestive enzymes and performing absorption villi - synthesize enzymes that will complete the digestive process - are also responsible for absorption - do not secrete any fluid - micro villi create a brush border (that retains the digestive enzymes) to which nutrients are brought in contact with by mixing movements of the intestine VILLI Cells - do NOT secrete fluid, but ABSORB nutrients, fluids. -SYNTHESIZE enzymes, retain them in brush border Enterokinase exception: is released into the lumen (trypsin activator) Amylase Lipase Aminopeptidases Dipeptidases DISACCHARASES - very specific SUCRASE substrates MALTASE ISOMALTASE nonfunctional. or not LACTASE-synthesized in lactose intolerance crypts of Luberkuhn - perform the function of alkaline, isotonic secretion of fluid, not enzymes - they are reatined in the micro villi brush surface of the villi - when movements of the intestine bring the nutrients in contact with the microvilli they are acted upon by the enzymes and immediately absorbed COLONIC SECRETION - SMALL VOLUME - digestion and absorption of nutrients is completed in the small intestine - ALKALINE [HCO3] = 100-150 mEq/L isotonic [K+] = 100-150 mEq/L - MUCIN (Lots!!!) -- participates in protection of the colon lubricates feces - NO DIGESTIVE ENZYMES - BACTERIAL ACTIVITY As a result of the secretory activity of salivary, gastric, pancreatic, hepatic, intestinal secretions, absorbable form: amylase disaccharases Polysaccharides Disaccharides Monosaccharides pepsin, trypsin peptidases Amino acids, Proteins Small Peptides Di, tripeptides chymotrypsin lipase, co-lipase Fats bile salts only substance that is produced by the liver that is involved in digestion produced by the pancreas Mono, Diglycerides, FAs regulation of intestinal secretions - local enteric reflexes - vaso-vagal reflexes - hormonal factors ABSORPTION WHAT? WHERE? HOW? HOW MUCH? H2O 2000 ml Solids 500g DAILY we pretty much digest everything or close to everything we ingest - most of the solids excreted are not of dietary origin 30% bacteria 30% undigested fiber 10-20% lipids 10-20% inorganic matter Solids 50g H2O 100ml - about 9L of fluid must be absorbed by the digestive tract daily - 42L of fluid in a 70kg person - half of ECF is recycled daily between the extracellular environment, to the lumen of the GIT and back 2L ingested **very large quantities of ions are also reabsorbed from the lumen of the GIT - all secretions with the exception of saliva are isotonic + Volumes of fluids entering GIT about 2L are absorbed in the colon and 7L in the small intestine 7 L of secretions 9L of total fluid reabsorbed PROTEIN RELEASE INTO LUMEN 50g as enzymes 30g as cells there is recycling of protein in very large quantities in the cells which undergo apoptosis millions of cells are shed into the gut on a daily basis the protein released by apoptosed cells are digested by proteases and are absorbed into the amino acid pool where they are reused 80g amino acids a.a. pool WHAT? Most of absorption is REABSORPTION! recycling of products - water, protein... WHERE? SITES OF EXCHANGE CHARACTERIZED BY 1. Very large surface areas for efficiency of transport 2. Intimate contact with blood vessels absorption takes place into blood vessels the bulk of absorption takes place in the small intestine: ideally suited to allow for absorption - no nutrients absorption takes place in the mouth (with the exception of small amounts of alcohol, some drugs) - there is some specialized absorption (but not nutrients) takes place in the oral cavity - the floor of the mouth is highly vascularized and will allow for the absorption of a nitroglycerine pill STRUCTURAL CONFIGURATION OF SMALL INTESTINE you can remove almost half of the entire small intestine and not compromise its ability to absorb everything you eat Only GI organ essential to life (colon cannot take over nutrient absorption) Area in excess of needs there are many folds and outpushings that increase the SA of the surface area VILLUS Postprandial Blood Flow to intestine is 1-2L/min. Lymph Flow is 1-2 ml/min - monosaccharides, amino acids, di/tripeprides. short chain fatty acids will be absorbed into the circulation - long chain fatty acids are not absorbed into the blood, but the central lymphatic channel called the lacteal MAJOR AREAS OF ABSORPTION DUOD. Iron Ca++ CHO JEJUNUM a little more is absorbed in the proximal region because the surface area and efficiency of absorption is higher in the proximal region - the majority of carbohydrates are absorbed by the time the meal reaches the distal region Prots. Lipids Na+ H2O even though bile acids are absorbed in the distal region, lipids can be absorbed all along the intestine ILEUM Vit B12 Bile Acids HOW ? Simple Diffusion Facilitated Diffusion Active Transport Pinocytosis Osmosis – water always follows the osmotic gradient generated by movement of ions What limits absorption? Requirements for Absorption Adequate digestion – Enzymes (activated), pH, all secretions ions released into the Adequate site for absorption Adequate transit time for absorption Adequate co-factors, transporters intrinsic factor intestine are alkaline and they neutralize gastric fluids - acidic secretions can inactivate intestinal enzymes if things move too quickly there is not enough time for adequate digestion and absorption - maintained by the stomach Carbohydrate Digestion and Absorption 6% 60% 30% X Lactose Intolerance dissacharases are in the brush border of microvilli and all products released into the capillary don't need details from this slide PROTEIN DIGESTION AND ABSORPTION 35-200g/d - the small dipeptides/tripeptides may be absorbed faster than individual amino acids Oligopeptides may be absorbed faster than free amino acids FAT DIGESTION AND ABSORPTION Lipase, co-lipase B.S. function of lipase, co-lipase, bile salts, micelle formation intestinal cell EFFICIENCY most of what is ingested is absorbed CARBOHYDRATE FAT PROTEIN 99% 95% 92% High efficiency results from effective coordination of activities at the interand intra-organ levels. physiological stimulus for activity in the GIT is the intake of a meal transit time is related to other functional activities in a given organ - the pharynx - 1s - esophagus - 10s - stomach - minutes to hours - intestine - several days - colon - hour s- days A wave of Cephalic secretory activity, preceding, accompanying, and trailing behind meal Gastric Also a wave of motor activity Intestinal which receives, accommodates and conveys meal accompanies the meal as it moves down the GIT permits a small amount of secretion from the stomach, but comes in full force in response to the liver, gall bladder and pancreas PROTECTIVE MECHANISMS • • • • • MUCIN lubricates the contents, prevents mechanical injury INACTIVE PROTEASES, TRYPSIN INHIBITOR “GASTRIC MUCOSAL BARRIER” SPHINCTERS PREVENT REFLUX NEGATIVE FEEDBACK INHIBITION OF GASTRIN • NEUTRALIZATION OF DUODENAL CONTENTS • MMC = “HOUSEKEEPER” migrating motor complex - restricted to the stomach and small intestine • Etc., etc. ...
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This note was uploaded on 04/26/2011 for the course PHGY 210 taught by Professor Trippenbach during the Winter '08 term at McGill.

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