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Digestive physiology Digestion & absorption GIT motility & circulation Ruminant & Pre-ruminant digestion Revision of digestive system in farm animals • http://www.powershow.com/view/1fb91N2JjM/Digestive_Physiology_of_Farm_Animal s_powerpoint_ppt_presentation Digestion and absorption • These are related but separate • Digestion: breakdown of complex molecules/nutrients into simple molecules • Absorption: process of transporting simple molecules across intestinal epithelium • Both are a result of biochemical events occurring in the gut • Both are important for nutrient assimilation • No absorption if food not digested • Digestion fruitless if no nutrient absorption • Various assimilation disturbances exist • Caused by a variety of diseases Digestion and absorption • • • • • Some diseases affect digestion while others absorption But signs often similar Therapies might be different Diagnosing cause is a challenge Diarrhea occurs if there’s mismatch btwn secretion and absorption Microanatomy of SI • • • • SI mucosa has large surface area Has epithelial cells with ‘leaky’ junctions btwn them Facilates contact btwn SI mucosa & luminal contents 3 levels of surface convolutions serve to expand surface area – Plicae circulares: large folds of mucosa, not present in all spp – Villi: finger-like projections in epithelium, present in all spp, increase SA 10-14 times – Brush border: submicroscopic microvilli, further increase SA • Base of villi has gland-like structures k.a. crypts of Lieberkuhn Microanatomy of SI • • • Villi & crypts covered with continuous layer of cellular epithelium Epithelial cells covering villi & crypts = enterocytes Enterocytes have two distinct cell membranes 1. – – – 2. – – Apical membrane covers cell surface facing lumen (apex) Contains microvilli Covered by jelly-like layer of glycoprotein k.a. glycocalyx Enzymes & other proteins attached to MV & project into glycocalyx Basolateral membrane Not in direct contact with ingesta Absorbed nutrients exit enterocytes thru basolateral membrane Microanatomy of SI • Attachments btwn adjacent enterocytes = tight junctions • Not necessarily tight at molecular stand point • Junctions form narrow band attachment btwn adjacent enterocytes near apical end • Allows free passage of water & some electrolytes • Lateral space btwn lateral surfaces of enterocytes • Distended & filled with ECF • ECF separated from fluid in the intestinal lumen by tight junctions • & from blood by basement membrane capillaries Microanatomy of SI • Both tight junctions & capillary endothelia are permeable barriers • Allow free passage of water & small molecules • Thus there’s relatively free flow of water & most electrolytes btwn SI lumen fluid & ECF in lateral space & blood Intestinal surface microenvironment • • • • • Made up of glycocalyx, mucus & unstirred water layer Goblet cells interspaced btwn enterocytes secrete mucus Mucus covers mucosa At brush border surface mucus blends with glycocalyx Form viscous coating that trap molecules near apical membrane • Near intestinal surface in the unstirred water layer • These form diffusion barrier thru which nutrient pass thru before entering enterocytes Digestion • Involves physical & chemical breakdown • Physical breakdown results in – Reduction in feed particle size – Allows food flow thru GIT – Increases surface area exposed to enzymes • Begins with mastication • Completed by grinding action of distal stomach • Physical action in stomach aided by chemical actions – enzymes (pepsin) & HCl • Chemical action breaks connective tissue Digestion • Physical breakdown complete when feed leaves stomach • Chemical digestion accomplished thru hydrolysis • Hydrolysis = splitting chemical bond by insertion of water molecule • Such bonds are – – – – Glycosidic linkages in CHO Peptide bonds in proteins Ester bonds in fats Phosphodiester bonds in nucleic acids • Enzymes catalyze hydrolysis Digestion • 1. 2. • Enzymes are of two general classes Those that act within lumen of gut Those that act at membrane surface of epithelia Lumen enzymes – – – – – – Originate from GI glands like salivary, gastric & pancreatic glands Thoroughly mixed with ingesta Actions thruout lumen of associated segments Catalyse luminal phase of digestion Results in incomplete nutrient hydrolysis Results in short chain polymers from original macromolecules Digestion • Membrane surface enzymes • Complete the hydrolytic process • Enzymes chemically bound to surface epithelium of SI • Break short chain polymers to monomers • Monomers absorbed across epithelia • = membranous phase of digestion • Followed by absorption Summary • Luminal phase – Large polymeric molecules (starch & protein) – Enzymes active in gut lumen (from salivary, gastric & pancreatic glands) • Membranous phase – Small polymer molecules (polysaccharides, peptides) – Enzymes active at surface of gut (synthesized in enterocytes & attached to apical membrane – Result in monomeric molecules for absorption (monosaccharides, amino acids) Regulation of GI function • Diverse & specialized processes take place in different sections • Fundamental consistency in anatomy of the GIT • Composed of 4 basic layers/tunics – – – – Tunica serosa Tunica muscularis Tunica submucosa Tunica mucosa • Mucosa most variable in structure & function Regulation of GI function Regulation of GI function Read more • http://www.vivo.colostate.edu/hbooks/pathp hys/digestion/index.html Quiz 1. Surface area of the small intestine is at three levels of surface convolutions : i. _______ circulares: Large _______ , not present in all species ii. _______ : finger-like epithelial projections Increase area by 10-14 fold iii. _______ border composed of _______ 2. _______ of Lieberkühn are highly mitotic, secretory cells at _______ of _______ 3. Mucus blends into the gelatinous _______ , forming a viscous molecule-trapping layer _______ : A layer of flowing water adhering to the intestinal epithelium Quiz answered 1. Surface area of the small intestine is at three levels of surface convolutions : i. Plicae circulares: Large folds, not present in all species ii. Villi: finger-like epithelial projections Increase area by 10-14 fold iii. Brush border composed of microvilli 2. Crypts of Lieberkühn are highly mitotic, secretory cells at base of villi 3. Mucus blends into the gelatinous glycocalyx, forming a viscous molecule-trapping layer 4. Unstirred water: A layer of flowing water adhering to the intestinal epithelium Small intestines Small intestines Small intestines Regulation of the GI function • Robust & complex mechanisms for control & communication • Involves nervous & endocrine systems - inbuilt GIT versions • Many DS diseases are associated with dysfunction of the relationship • Regulation of GI function achieved thru – Enteric/Intrinsic NS – Enteric/intrinsic ES – Motility of GI Enteric/Intrinsic nervous system • Influences motility, ion transport & GI blood flow • Control partly emanates from CNS • Local NS k.a. enteric or intrinsic NS • ENS has immense complexity and magnitude • Has as many neurons as the spinal cord • Principal components – 2 neuron networks/plexuses embedded in GI wall • Extend from esophagus to anus Intrinsic NS • Intrinsic motor nerves innervate – Vascular muscle – Gut muscle – Glands in gut wall • Gut smooth muscle innervation different from skeletal muscle • No direct synaptic junction btwn GI nerve & muscle fibres • Axons end in vesicular structures (varicosities) • Contain neuroregulatory transmitter substances Intrinsic NS • Secreted by nerves in response to action potential • Affect actions of nearby muscles or glandular cells • Either inhibitory or stimulatory • Gut also receives extrinsic innervation from ANS • Parasympathetic & sympathetic NS form link • Link btwn intrinsic NS &CNS Enteric nervous system • Myenteric plexus – Located btwn longitudinal & circular layers of muscle in the tunica muscularis – Exerts control primarily over GI motility • Submucusa plexus – – – – – Buried in submucosa Senses env within lumen Regulate GI blood flow Control epithelial cell function Sparse and missing in some sections where these functions are minimal such as the esophagus • There are also minor plexuses beneath serosa Enteric nervous system The arrangement of the enteric plexuses, depicted for the small intestine. A: appearance in separated layers. The myenteric plexus, consisting of numerous ganglia and connecting nerve fibre bundles, lies between the longitudinal and circular muscle layers. A second ganglionated plexus is in the submucosa. These plexuses provide nerve fibre plexuses in the muscle, in the mucosa and around arterioles. B: The enteric plexuses shown in a cross section of the intestine Enteric nervous system • Enteric plexuses have three types of neurons – sensory, motor & interneurons • Sensory neurons – Receive info (sensory input) from receptors in mucosa & muscle – Different types identified – Respond to mechanical, thermal, osmotic and chemical stimuli Enteric nervous system • Mechanoreceptors (muscular layers) • Monitor distension • Chemoreceptors (mucosa) – Monitor chemical conditions in lumen • Thermal – Monitor temperature • Osmotic – Monitor ion concentration • Baroreceptors – Monitor pressure Intrinsic NS • Motor neurons – Control motility & secretion, possibly absorption – Have large # of effector cells – smooth muscle, secretory cells, GI endocrine cells • Interneurons – Integrate msg from sensory neurons & provide it to motor neurons Enteric nervous system • Uses various neurotransmitters • Acetylcholine is the major one – Generally neurons using Ach are excitatory. – Stimulate: • • • • smooth muscle contraction, increases in intestinal secretions, Release of enteric hormones and Dilation of blood vessels • Norepinephrine also used extensively – Derives from extrinsic sympathetic neurons – Effect is almost always inhibitory Enteric nervous system • Functions autonomously • Note: digestion requires communication links with CNS • Parasympathetic & sympathetic fibers connect CNS & ENS • Or connect CNS directly to GIT • Thru this gut provides sensory info to CNS & CNS can affect GI function • Signals from outside DS relayed to DS e.g. sight of appealing food stimulates stomach secretions Extrinsic Innervation • Most of GIT receives parasympathetic innervation from vagus nerve • Part of terminal colon innervation thru pelvic nerve • Preganglionic fibers synapse on cell bodies of intrinsic system • Extrinsic sympathetic fibres enter gut thru post ganglionic fibres • Sympathetic fibres synapse on neurons of INS • Others have direct effect on GI muscles & glands Enteric/Intrinsic endocrine system • • • • • • • • • • Hormones from many endocrine glands affect DS fxn Most profound effect from enteric hormones GIT is largest endocrine organ in the body Three hormones best studied are gastrin, CCK & secretin EES is diffuse with single hormone-secreting cells scattered in mucosa E.g. stomach G cells are scattered among epithelial cells Hormones synthesized within cells & secreted into blood Hormones secreted in response to fairly specific stimuli Endocrinocytes respond to changes in env within DS lumen Their apical border is in contact with lumen & continuosly ‘taste’ luminal env Enteric/Intrinsic endocrine system • Illustration of control: SI – Ingesta from stomach = acidic – SI is basic – Presence of acidic ingesta stimulates secretin secretion – Secretin stimulates basic pancreatic secretions that neutralize SI lumen contents • ENS & EES interrelated Enteric/Intrinsic endocrine system • • • • • • • • Extensive # & variety of endocrine cells Usually grouped together into gland GI endocrine cells thruout gut epithelium Broad base & narrow apex Narrow apex exposed to lumen Sample luminal contents Secretory granules in base Storage form of hormones Endocrine cell Enteric/Intrinsic endocrine system • • • • • • • • Anatomy allows sensing lumen changes Respond by releasing hormones Hormone released into mucosal area Absorbed in blood stream Not secreted into gut lumen Each E cell has characteristic distribution E.g. gastrin producing cells mostly in distal stomach Cholecystokinin in SI esp proximal region Major GI hormones Hormone Site of production Action Release stimulus Gastrin Distal stomach 1o: stimulates acid secretion from stomach glands 2o: gastric motility; stomach epithelium growth Protein in stomach; high gastric pH; vagal stimulation Secretin Duodenum 1o: bicarbonate secretion from Acid in pancreas duodenum 2o: biliary bicarbonate sec Cholecystoki nin (CCK) Duodenum - 1o: enzyme secretion from ileum pancreas 2o: inhibits gastric emptying Proteins & fats in SI Major GI hormones Hormone Site of production Action Release stimulus Gastric Duodenum + inhibitory upper peptide (GIP) jejunum 1o: inhibits gastric motility & secretory activity 2o: stimulates insulin secretion if sufficient glc present CHO & fats in SI Motilin 1o: regulates motility patterns btwn meals 2o: may regulate tone of lower esophageal sphincter Acetylcholine Duodenum + jejunum GI motility & circulation GI motility • Muscle contractions & motility are integral parts of digestive fxn • There are two fundamental patterns of motility • Propulsion principally thru peristalsis • Mixing thru segmentation contractions esp in SI • These facilitate digestion and transportation of ingesta GI motility: peristalsis GI motility: mixing GI motility • Continuous contractions occur • The faster the contractions the faster the ingesta movements • More contractions when feeding than at rest • Amplitude of contractions vary GI motility - parasympathetic • Acetylcholine • Very specific control • Increase GIT activity by – Promoting peristalsis – Relaxing sphincters – Increase rate of glandular secretion • Mouth & stomach • Small & large intestine are largely controlled by local factors GI motility - sympathetic • Norepinephrine • Mass discharge (all or nothing) • Decrease GIT activity by – Decreasing peristalsis – Contracting sphincters – Can totally inhibit movement Gastric motility • Fundus/corpus – Storage, volume adaptation (receptive relaxation) – Muscle cells partially contracted at resting membrane potential • Hyperpolarization leads to relaxation and increased volume – Relaxation under parasympathetic control • Swallowing, esophageal & stomach distension • Antrum – pumping action, – contractions every 3-5 min, vagal stimulation • Pyloric sphincter mixes by blocking passage, coordinated flow (2-10 ml/min) Gastric secretion & motility • • • • • • • • Under neural & humoral mechanisms Neural: local autonomic reflexes Involve cholinergic neurons & impulses From CNS thru vagus nerve Humoral: hormones e.g. gastrin, CCK Vagal stimulation increases gastrin secretion Some vagal fibers direct stimulation of fundus cells Increase acid & pepsin secretion Gastric motility & emptying • • • • • • • • • Entry of feed in stomach Organ relaxes by reflex Process of receptive relaxation Triggered by pharynx & esophagus movement Peristaltic contractions follow Mix & squirt feed into duodenum Controlled rate Peristaltic wave, most marked in distal stomach When well developed occur 3/min Gastric motility & emptying • Rate of emptying into duodenum depend on feed type • CHO rich feed leaves stomach in few hrs • Protein –rich feed leaves slowly • Slowest emptying with meal containing fat SI motility • Coordinated contractions facilitate digestion and absorption • Chyme mixed with digestive enzymes from pancreas and bile salts from biliary system • Nutrient molecules in lumen constantly dispersed, • Allows epithelial contact to complete enzymatic digestion and absorption • Chyme moves down – making way for next load – eliminating indigestible/ toxic substances • Two cycle states, each with distinctive patterns of motility (mixing & peristalsis) – Interdigestive – Feed state Migrating motor complex (MMC) • Interdigestive period (between meals) – lumen largely devoid of contents – housekeeping contractions propagate from the stomach through the entire small intestine, sweeping it clear of debris. – Complex pattern of motility – the cause of "growling". Migrating motor complex (MMC) • Fasting motility in stomach & SI • Phase I – inactive 30-60 min • Phase II – irregular 20 – 40 min – ½ segmentary ½ peristaltic • Phase III – intense contractions – ¾ peristaltic – 10-20 min • Phase IV – spiking activity subsides The interdigestive motility pattern – 0-5 min (migrating motor complex) is organised in cycles of activity and quiescence Migrating motor complex • • • • Cycle last 80-120 min Develops 4-5 hrs after meal Starts in stomach and moves to ileum Starts over when reaches terminal ileum (one part always active) • May be only motility pattern for non-meal feeders (cattle) Migrating motor complex functions • House keeping –Sweep debris and bacteria down GIT –Bacterial overgrowth is likely without phase III • Muscle tone – helps keep muscle functional Feed state motility (FSM) • Following a meal (Chyme presence) – segmentation contractions: chop, mix and roll the chyme – peristalsis slowly propels it toward the large intestine • • • • Duodenum contracts 2 -3 times per antral wave Moves ingesta down Segmentary rhythmic mixing Peristaltic moving of ingesta – move 4-8 inches per wave (mixing inevitable) Feed state motility (FSM) • Continuous irregular motility (phase II of MMC) • ½ segmentary & ½ peristaltic • Simultaneous activity through stomach & SI • Begins with eating • Last 4 to 5 hours after a meal SI motility regulation • Controlled predominantly by excitatory and inhibitory signals from enteric nervous system • Modulated by – inputs from ANS & CNS, – gastrointestinal hormones • Coordinated movement from stomach down • Feedback inhibition optimize digestion & absorption • Duodenal & jejunal receptors sense caloric chyme content • Increased content inhibit stomach contractions Large intestine • • • • Extended retention of ingesta (1-2d) Proximal (storage fermentation) Distal (elimination of fecal waste) Haustrations – Not rigid or stationary – Reduce transit rate – Increase retention time Large intestines • Motility – Single haustra contractions – Some sequential contractions – Move orally in proximal colon – delayed transit – Move backwards in distal colon – increased transit – Few peristaltic contractions Large intestines • Mass movements – Occurs several times/day, usually after meal – Disappearance of haustral folds – Contractions move caudally propelling digesta to distal colon/rectum – After movement haustral folds return – Parasympathetic –increases motility – Sympathetic – decreases motility GI circulation • Main arteries – Celiac – stomach, spleen, part of pancreas – Hepatic - 1/3 of blood flow – Superior mesenteric – SI, part of pancreas of LI – Inferior mesenteric – main supply to LI • Veins – Portal vein - Drains blood from GI – PDV = portal drained viscera – Hepatic vein drains nearly all splanchic blood Intestine circulation • Most perfused tissues in body – Each villus with own vein and artery – 50-60% blood to liver & SI • PDV receives 30-35% of total cardiac output • Increase in dietary intake increases flow to PDV – Increased cardiac output – %PDV remains relatively constant • 75% to mucosa & submucosa – very metabolically active • 25% to muscularis & serosa Counter-current mechanism • Allows water/solute to pass from arteriole to venule without passage through capillary bed • Arteriole <20 µm from venule • Vasculature has limited permeability – Na+ cannot pass without transporter – H2O & O2 can pass Hunger contractions • Stomach musculature rarely inactive • After emptying, mild peristaltic contractions begin • Gradual intensity increase • More intense, mildly painful • Associated with hunger sensation • Interaction with feeding & satiety centres in brain Vomiting • • • • • • • • • Visceral reflex Starts with salivation & nausea sensation Glottis closes Prevents vomitus aspiration into trachea Contraction abdominal wall muscles Increase intra-abdominal pressure Chest in fixed position Esophagus & gastric cardiac sphincter relax Reverse peristalsis begins Vomiting • Gastric contents ejected • Vomiting centre in medulla oblongata regulates • Stimulated by – upper GIT mucosa irritation – Chemoreceptors stimulated by circulating chemical agents – Emotionally charged stimuli e.g. smells, sight Absorption • Substances pass thru lumen of GIT into circulation • Different ways – – – – – – Diffusion Non-ionic diffusion Facilitated diffusion Solvent drag Active transport Endocytosis Absorption • Movement of products of digestion across intestinal mucosa into vascular system for distribution • Need to understand – – – – – Processes of diffusion Differences in composition of ICF & ECF Electrical polarity across membranes Na+, K+ ATPase pump Selective ion channels • Uses specialized nutrient transport systems • Exist in apical & basolateral membranes • Involve specific proteins embedded in membranes Absorption • Proteins provide transport pathway • Interact with specific organic nutrients & inorganic ions to effect their transport across membranes • Transport mechanisms classified as – – – – active, secondary active, tertiary active and passive Absorption • Active transport – – – – Involves direct consumption of metabolic energy – ATP ATP expended to move ions/molecules against electrical/chemical gradient Na+,K+-ATPase pump important transport pathway Lies in basolateral membrane • Secondary & tertiary active tranport – Utilize transcellular Na+ ion electrochemical gradient as source of energy • Passive transport – Occurs either thru ion channels in cell membranes – Or directly thru the tight junctions Water & Na+ Absorption • Na+ actively absorbed by SI to absorb water from lumen • Water movement follows Na+ via osmotic gradient • Water moves out of arteriole to venule due to Na+ gradient created from venule to arteriole • Increased Na+ conc in arteriole pulls water from lumen Summary • Digestion & absorption depend on mechanisms that: – Propel feed thru GIT – Soften feed – Mix feed with bile & digestive enzymes • Mechanisms involve – Dependence on intrinsic properties of intestinal muscle – Operation of visceral reflexes – Action of hormones • GI Motility and circulation designed to suit and facilitate both digestion and absorption