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Description : Check out this medical presentation on Digestive System, which is titled "GI physiology review", to know about the function of the GI system (MOTILITY, SECRETION, DIGESTION, and ABSORPTION).

Tags : Digestive System, GI physiology, MOTILITY, SECRETION, DIGESTION, ABSORPTION

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Slide 1-

GI physiology review
Slide 2-

Function of the GI system 4 basic digestive processes • MOTILITY • SECRETION • DIGESTION • ABSORPTION
Slide 3-

3 Delay of 3 seconds
Slide 4-

Sphincters 3
Slide 5-

Mucosa • epithelium • lamina propria: • muscularis mucosae • exocrine cells • endocrine/paracrine cells Submucosa • connective tissue, blood vessels, glands • submucosal nerve plexus (Meissner’s plexus) Muscularis externa • smooth muscle cell layer inner circular layer outer longitudinal layer • myenteric nerve plexus (Auerbach’s plexus) Serosa (adventitia)
Slide 6-

Autonomous smooth muscle function Neural regulation extrinsic NS (CNS) intrinsic NS GI hormones Paracrine mediators humoral regulation pacemaker activity electrical coupling Regulation of GI function 5
Slide 7-

Autonomous smooth muscle function Intestinal smooth muscle cells: effector organ of GI motility Pacemaker activity: Thin layer of interstitial cells (interstitial cells of Cajal) between circular and longitudinal cell layer. Conduction through gap junctions.
Slide 8-

Excitation-contraction coupling intestinal smooth muscle Contraction requires an increase of cytosolic calcium ([Ca2+]i) Electro-mechanical coupling: Contractions are triggered by action potentials (APs) that travel from cell to cell through gap junctions. Pharmaco-mechanical coupling: Contraction occur in the absence of action potentials e.g. in response to neurotransmitter or hormones. 5
Slide 9-

Thin layer of interstitial cells (interstitial cells of Cajal) between circular and longitudinal cell layer. Conduction through gap junctions. Pacemaker activity:
Slide 10-

GI smooth muscle electrophysiology and contraction Resting membrane potential -40 to -80 mV. membrane potential oscillations Na+/K+-ATPase. Slow waves Pacemaker activity Ionic events during slow waves: Na-, Ca- and K-currents Modulation by enteric neurons Action potentials when slow-waves reach electrical threshold: burst of APs (10-20 ms, rising phase is carried by Na+ and Ca2+ ions) 6
Slide 11-

Smooth muscle tone and contraction • Contraction begins when depolarizing phase reaches mechanical threshold. • Development of muscle tone and contraction correlate with the degree of depolarization • can occur in the absence of APs. • Baseline tension is ‘non-zero’ (constant basal tone). • Tonic contractions: contractile tension that is maintained for prolonged periods of time. • Phasic contraction: “twitch-like” contraction evoked by action potentials. Triggering of APs increases strength of contraction. Frequency and number of APs grade the degree and duration of contraction.
Slide 12-

7
Slide 13-

Neurotransmitters of the autonomic nervous system 2 10 sympathetic parasympathetic
Slide 14-

Integration of sympathetic, parasympathetic and enteric nervous system 12
Slide 15-

Sympathetic efferent innervation • Primarily via postganglionic adrenergic fibers with cell bodies in prevertebral and paravertebral plexuses (celiac plexus, superior and inferior mesenteric plexus, superior and inferior hypogastric plexus) terminate in submucosal and myenteric plexus. • Typically inhibitory effect on synaptic transmission in the enteric plexuses. • Effects of sympathetic activity - vasoconstriction of gastrointestinal blood vessels - inhibition of glandular function - muscularis externa: inhibition of motor activity - contraction of muscularis mucosae and certain sphincters
Slide 16-

Parasympathetic efferent innervation • Vagus nerve (upper gastrointestinal tract to transverse colon) and parasympathetic fibers of pelvic nerves from the hypogastric plexus Predominantly cholinergic fibers that terminate on ganglion cells of intramural plexuses. • Stimulation of motor (smooth muscle cells) and secretory activity.
Slide 17-

Enteric nervous system semi-autonomous nervous system in the wall of the GI tract ("the little brain in the gut"): major network of ganglia and interconnecting neurons (about 108 neurons!) 2 major plexuses • myenteric plexus (Auerbach’s plexus) • submucosal plexus (Meissner’s plexus) 11
Slide 18-

Integration of neuronal control of GI function 13
Slide 19-

Example of enteric reflex: The neural circuit for peristaltic propulsion of GI (the”law of intestine”). Stretching a segment of the GI tract is sensed by sensory enteric neurons. This signal is transmitted via excitatory and inhibitory interneurons to excitatory (proximal) and inhibitory (distal) motor neurons, causing ascending excitation and descending inhibition of smooth muscle cells -->GI content is transported in aboral direction 14 VIP = vasoactive intestinal peptide
Slide 20-

Intestinal reflexes Short range reflexes: Food bolus causes aboral relaxation and proximal contraction --> food transport in orthograde direction (law of the intestine). Regulated by intrinsic nerves.
Slide 21-

• Gastro intestinal hormones are released from distant endocrine cells and transported by blood streamto activate secretion (e.g. gastrin from G cells activate HCl secretion) • Paracrine mediators are released into the neighborhood of secretory cell and reaches target cells by diffusion (e.g. histamine = paracrine agonist for gastric HCl secretion). 58
Slide 22-

Important actions of GI hormones (compare with table 15) Action Gastrin CCK Secretin GIP Acid secretion S I I Pancreatic HCO3- secretion S S Pancreatic enzyme secretion S Bile HCO3- S Gallbladder contraction S Gastric emptying I Mucosal growth S Pancreatic growth S S S = stimulates; I = inhibits
Slide 23-

Additional GI hormones Hormones are produced by enteroendocrine cells in the GI tract in stomach, small and large intestine Motilin Serotonin Substance P Vasoactive intestinal peptide (VIP) Neurotensin increases intestinal motility increases intestinal motility increases intestinal motility neurotransmitter for intestinal smooth muscle stimulates secretion of water and ions decreases intestinal motility increases blood flow to ileum 16
Slide 24-

Additional GI hormones (cont.) Glucagon Entero-glucagon Glicentin (glucagon-like substance) Somatostatin Urogastrone (Epidermal Growth Factor) Histamine stimulate hepatic glycogenolysis stimulates hepatic glycogenolysis local inhibition of other endocrine cells (e.g. G-cells) inhibits secretion of HCl increases epithelial growth increases secretion of HCl
Slide 25-

Gastrointestinal paracrine mediators Paracrine agonists released by: - paracrine cells - GI immune system - antibodies - inflammaory mediators (prostaglandins, leukotrienes, cytokines, histamine, others) 3 4 Epithelium Lamina propria Muscularis mucosae Submucosa Circular muscle Longitudinal muscle Villus Lymph node Serosa Myenteric plexus Submucosal plexus Gland in submucosa Muscularis externa
Slide 26-

GI immune system - half of the mass of immune cells in the body are in the GI tract - antibody secretion to specific food antigens - immunologic defense against pathogenic microorganisms
Slide 27-

Pancreatic Hormones Pancreatic hormones: insulin glucagon somatostatin produced and secreted (endocrine pancreatic secretion) by the islets of Langerhans essential for the regulation of metabolism
Slide 28-

Autonomous smooth muscle function Neural regulation extrinsic NS (CNS) intrinsic NS GI hormones Paracrine mediators humoral regulation pacemaker activity electrical coupling Regulation of GI function > high degree of integration > high degree of autonomy 5
Slide 29-

Example: acid secretion by gastric parietal cell.... + gastric motility enhances mixing of food and disgestive juices 71 cholinergic nerve terminals G-cells H+
Slide 30-

muscular contractions that mix and move the contents of the gastro-intestinal tract to the appropriate sites of digestion and absorption MOTILITY
Slide 31-

Patterns of GI motility Type of contraction Organ/structure • Tonic contractions upper and lower esophageal sphincters pyloric valve sphincter of Oddi ileocecal valve internal anal sphincter • Propulsive peristalsis esophagus lower 2 thirds of stomach small intestine rectum
Slide 32-

Patterns of GI motility (cont) Type of contraction Organ/structure • Reverse peristalsis (antipropulsion) proximal colon • Mass movements ascending, transverse and descending colon • Nonpropulsive segmentation small intestine • Haustration ascending, transverse and descending colon
Slide 33-

Patterns of GI motility (cont) • Migrating motor complex = migrating myoelectric complex fasting/empty small intestine
Slide 34-

Esophagus Tubular conduit (about 20 cm long) for food transport from mouth to stomach. Structural and regulatory aspects: • Upper third of the esophagus: circular and longitudinal muscle layers are striated; innervation via cranial nerve. • Middle third: coexistence of skeletal and smooth muscle. Primary innervation from vagus nerve; nerve input from neurons of myenteric plexus • Lower third: smooth muscle, enteric nerve system (input from vagus nerve to enteric nerve system).
Slide 35-

Neuronal control of esophagus Pharynx UES Swallowing center 18 Innervation afferent: sensory feedback to swallowing center efferent: • vagal somatic motor neurons to striated muscle • vagal visceral motoneurons to smooth muscle, terminating at neurons of myenteric plexus 3 1 2 1 2 3
Slide 36-

Esophageal sphincters • Upper esophageal sphincter (UES): prevents entry of air • Lower esophageal sphincter (LES): LES = zone of elevated resting pressure (~ 30 mm Hg) prevents reflux of corrosive acidic stomach content. LES tone is regulated by extrinsic and intrinsic nerves, hormones and neuromodulators. Contraction: vagal cholinergic nerves (nicotinic, i.e. atropine insensitive) and sympathetic nerves (-adrenergic). Relaxation: primary peristalsis --> inhibitory vagal nerve input to circular muscle of LES (neurotransmitters (VIP and NO) and reduced activity of vagal excitatory fibers (cholinergic, nicotinic). 32
Slide 37-

Swallowing Swallowing can be initiated voluntarily, but then it is under reflex control. Swallowing reflex = sequence of events that result in propulsion of food from the mouth to the stomach 1. Oral/voluntary phase 2. Pharyngeal phase 3. Esophageal phase
Slide 38-

Control of esophageal motility Local and central circuits 31
Slide 39-

Esophageal pressure profile 32
Slide 40-

Intraluminal esophageal pressure profile 0 mm Hg = ambient pressure Pressure in the body of esophagus is negative, reflecting intrathoracic pressure pressure wave during swallowing
Slide 41-

Stomach 33
Slide 42-

Functions of stomach motility • reservoir for large volumes of food • fragmentation of food and mixing with gastric secretion --> digestion • controlled emptying of gastric content into duodenum
Slide 43-

Reservoir Sphincter Mixing + Transport
Slide 44-

• Gastric filling Empty stomach (volume approx. 50 ml) can expand to > 1 liter; volume increase is n o t paralleled by similar increase of intragastric tension because of • Plasticity: stomach smooth muscle cells can be stretched (within limits) without a change in tension (developed force). • Receptive relaxation: Filling (gastric distension) causes reflective relaxation of the fundus and body of the stomach; reflex is mediated by vagus nerve (VIP and NO as neurotransmitters).
Slide 45-

• Gastric mixing Chyme = mixture of gastric secretion and food content 36
Slide 46-

• Gastric emptying • antral peristaltic contractions • pylorus regulates emptying • neural and humoral/hormonal fine regulation gastric duodenum/jejunum factors outside GI system
Slide 47-

Pyloric valve - regulates emptying of gastric content - prevents regurgitation of duodenal content Pyloric relaxation: inhibitory vagal fibers (mediated by VIP and NO). Pyloric constriction: excitatory cholinergic vagal fibers, sympathetic fibers and hormones cholecystokinin, gastrin, gastric inhibitory peptide and secretin. 37
Slide 48-

• Gastric factors Volume of chyme: increased volume (distension) stimulates motility Fluidity: increased fluidity allows more rapid emptying
Slide 49-

• Duodenal/jejunal factors 37 CNS
Slide 50-

Small intestine motility
Slide 51-

Types of motility of the small intestine • digestive motility pattern: segmentation peristalsis • interdigestive motility pattern: migrating myoelectric complex
Slide 52-

Segmentation • Most frequent type of motility • Closely spaced contraction of the circular muscle layer, dividing the small intestine into small neighboring segments. In rhythmic segmentation the sites of circular contractions alternate --> mixing • Frequency of segmentations decreases in aboral direction (11-12/min duodenum; 8-9/min ileum) --> slow forward transport of food content 53
Slide 53-

Peristalsis • Progressive contraction of successive sections (short distances) of circular smooth muscle in orthograde direction.
Slide 54-

Contractile activity of the muscularis mucosae Irregular contractions of sections of the muscularis mucosae (3/min) --> change in topography of the internal surface of the gut --> enhancement of the contact between mucosa and content and facilitation of absorption. Increased emptying of central lacteals and increased intestinal lymph flow. 4
Slide 55-

Emptying of the ileum Ileocecal sphincter: normally closed. Short-range peristalsis in terminal ileum and distension relaxes IC sphincter --> small amount of chyme is squirted into the cecum. Distension of cecum contracts IC sphincter. Gastro-ileal reflex enhances ileal emptying after eating. The hormone gastrin relaxes ileocecal sphincter. 54
Slide 56-

The migrating myoelectric complex (MMC) = migrating motor complex • occurs in fasted organism • bursts (lasting 5-10 minutes) of intense electrical and contractile activity that propagate from stomach (origin) to the terminal ileum. Repeats every 75-90 minutes. ligament of Treitz: duodenum-jejunum border 43
Slide 57-

Motility of the colon • Haustration (corresponds to segmentation in small intestine) • Segmental propulsion or systolic multihaustral propulsion • Antipropulsion (reverse peristalsis) • Mass movement
Slide 58-

Defecation Complex behavior involving voluntary actions and reflexes. Defecation reflex: sacral spinal cord and efferent cholinergic parasympathetic fibers in pelvic nerves. Distension of rectum and relaxation of internal sphincter. Voluntary actions: relaxation of external sphincter (striated muscle, innervated by somatic fibers via pudendal nerves) and increase of intraabdominal pressure 57
Slide 59-

exocrine glands secrete digestive juices, consisting of water electrolytes specific organic constituents important for digestive process (enzymes, bile salts, mucus) endocrine glands: hormones for regulation of the GI system SECRETION
Slide 60-

Functions of GI secretion are • digestive • protective For example..... • provide enzymatic machinery for degradation of nutrients • provide factors to facilitate absorption (e.g. bile salts, intrinsic factor) • lubricate food bolus • provide the proper ionic and osmotic milieus (e.g. pH) for enzymatic hydrolysis and absorption • aid in repair, replacement and barrier functions of the intestinal epithelium (e.g. epidermal growth factor) • contribute to body fluid homeostasis • immunological functions through secretory immunoglobulins (antibodies) and antibacterial compounds
Slide 61-

Secretagogue = substance that stimulates a secretory cell to secrete • neurocrine secretagogue: neurotransmitters released from neurons that innervate the secretory cell (e.g. ACh from vagus nerve) • endocrine secretagogue: hormones released from distant cells and transported by blood streamto activate secretion (e.g. gastrin from G cells activate HCl secretion) • paracrine secretagogue: released into the neighborhood of secretory cell and reaches target cells by diffusion (e.g. histamine = paracrine agonist for gastric HCl secretion). 58
Slide 62-

Mechanism of exocrine gland secretion Exocrine gland cells extract from the plasma raw materials necessary for the synthesis of secretion products. Secretion products are emptied into the ducts of the secretory gland and delivered to the GI tract. Secretion-blood flow coupling secretion is coupled with increased blood flow to the exocrine gland (functional hyperemia) to optimize availability of raw materials. 59
Slide 63-

Intracellular mechanisms • secretagogues bind to surface membrane receptors and stimulate secretion • intracellular messengers: • cAMP • IP3 and Ca2+ • activation of kinases --> altered ion channel function --> secretion 60
Slide 64-

Salivary glands • parotid • submandibular (submaxillary) • sublingual • (minor glands in labial, palatine, buccal, lingual and sublingual mucosa)
Slide 65-

Structure of salivary glands acinus = secretory endpiece with • serous acinar cells with zymogen granules (salivary amylase, salivary proteins) • mucous acinar cells secrete glycoprotein mucins ducts = drainage system modifications of acinar secretions • intercalated ducts • striated (intralobular) ducts • excretory (interlobular) ducts. 61
Slide 66-

Composition of saliva • electrolytes • proteins • mucin (glycoproteins --> viscosity) • digestive enzymes (salivary amylase stored in zymogen granules, released into acinar lumen by exocytosis) • protective proteins (secretory IgA) • water
Slide 67-

Protective function • bicarbonate (neutralization of acid produced by bacteria and gastric reflux) • antibacterial (lysozyme) • lactoferrin (binds Fe, decreases bacterial growth) • secretory immunoglobulin (IgA) • epidermal growth factor • mouth hygiene • facilitates speaking Digestive function • -amylase (= ptyalin) • lingual lipase • lubrification food for swallowing • dissolving substances for taste mechanism
Slide 68-

2-stage model of salivary secretion • Primary secretion product (acinus) is nearly isotonic with plasma. • Secondary modification in ducts extract Na+, Cl-, and add K+ , HCO3-, resulting in a hypoosmotic (hypotonic) secretion. 62
Slide 69-

• Composition and osmolarity dependent on secretion rate 63
Slide 70-

Mucus • Collective term for secretions that contain glycoprotein mucins which are characteristically viscous and sticky. • Protects mucosal surfaces from abrasion by food contents, lubricates the food bolus in the upper GI tract and alkaline pH counters regional acidity (e.g. stomach). • Mucus is produced by various cells in the GI tract: mucous cells in salivary glands goblet cells Brunners gland neck cells of gastric glands pancreatic acinar cells.
Slide 71-

Regulation of salivary secretion • The primary physiological control of salivary gland function is by the parasympathetic nervous system! • the sympathetic nervous system and hormones contribute to regulation
Slide 72-

Regulation of salivary secretion Autonomic nervous system: • Parasympathetic (ACh, VIP): • high and sustained output • synthesis and secretion of amylase and mucins • transport activity of ductular epithelium • vasodilation and increased blood flow • positive feed back on blood supply through kallikrein kininogen system • stimulation of glandular metabolism and growth • Sympathetic: • transient increase of secretion • vasoconstriction leads to decrease of salivation VIP= vasoactive intestinal peptide
Slide 73-

Gastric mucosa: cardiac glandular region oxyntic glandular region pyloric glandular region...... .........with a variety of secretory cells 35
Slide 74-

Secretory cells Secretion product • surface mucous cells, mucous neck cells mucus, HCO3- • oxyntic (= parietal) cells HCl, intrinsic factor • chief (= peptic) cells pepsinogen, gastric lipase • neuroendocrine cells G cells gastrin D cells somatostatin
Slide 75-

Digestive functions • digestive enzymes: pepsinogen (endopeptidase) gastric lipase • HCl secretion (parietal cells): acidic environment for pH optimum (1.8-3.5) of digestive enzyme pepsin (activated from pepsinogen) and lingual lipase (pH optimum 4). HCl softens food • Intrinsic factor: binds Vit B12 and protects from gastric and intestinal digestion Protective functions • gastric acidity: antibacterial • mucus and HCO3-: protective layer against damage of gastric mucosa by low pH
Slide 76-

Pepsinogen secretion • Pepsin = protease (endopeptidase) • Low gastric pH converts proenzyme pepsinogen into active pepsin; pepsin itself proteolytically cleaves pepsinogen (positive feedback) • Optimum for proteolytic activity is around pH 3. • ACh, gastrin, secretin, cholecystokinin and acid stimulate pepsinogen secretion. • Pepsinogen is stored in zymogen granules and released by exocytosis.
Slide 77-

Ionic composition of gastric juice Rate of secretion of gastric acid: • basal rate = 1-5 mEq/hr • maximal stimulation = 6-40 mEq/hr • higher in patients with duodenal ulcers • low flow rate: hypotonic • high flow rate: nearly isotonic, mainly HCl 66 63 Plasma Gastric juice
Slide 78-

Cellular mechanism of HCl production • Carbonic anhydrase drives HCO3- production • H+/K+ pump (ATP-dependent) drives H+ out and Cl- follows (via electrogenic anion channel) • HCO3-/Cl- exchange maintains Cl- supply • Alkaline tide: net HCO3- release into the blood stream during gastric acid secretion. 67 omeprazole -
Slide 79-

Regulation of acid secretion 68
Slide 80-

Gastric mucosal barrier • (1) unstirred, bicarbonate rich mucus layer maintains pH 7 at cell surface and protects gastric mucosa from gastric juice (pH 2) • (2) tight junctions between gastric mucosal cells prevent penetration of HCl between cells • (3) luminal membrane of gastric mucosal cells is impermeable for protons Protection against self-digestion 70
Slide 81-

Pancreatic secretion
Slide 82-

Secretory functions of the pancreas: • endocrine pancreatic secretion (islets of Langerhans): hormones (insulin, glucagon, somatostatin) essential for regulation of metabolism • exocrine pancreatic secretion: • aqueous component • enzyme component 98
Slide 83-

Digestive function • production and secretion of digestive enzymes • neutralization of acidic chyme (pancreatic enzymes pH optimum near neutral pH) Protective function • neutralization of acidic chyme --> protection from acid damage of intestinal mucosa
Slide 84-

Pancreatic enzymes Enzyme specific hydrolytic activity
Slide 85-

• Proteolytic enzymes are secreted in inactive zymogen form. Enteropeptidase (= enterokinase) secreted by duodenal mucosa activates trypsinogen (--> trypsin). Trypsin activates itself and the other proteolytic enzymes. • Trypsin inhibitor: protein in pancreatic secretion that prevents premature activation of proteolytic enzymes in pancreatic ducts • -amylase is secreted in active form Enzyme activation
Slide 86-

pH, osmolarity and electrolyte composition of pancreatic secretion 71
Slide 87-

Cellular mechanism of pancreatic secretion: • carbonic anhydrase reaction produces H2CO3 • Na/H exchange and H/K-ATPase eliminate H+ • Cl-/HCO3- exchange secretes bicarbonate into duct lumen • electrogenic Cl- channels recycle Cl- back into lumen • Acid tide: net H+ release into the blood stream during pancreatic secretion. 72 Carbonic anhydrase
Slide 88-

Bile secretion and liver function
Slide 89-

Structure of the liver 96
Slide 90-

blood flow bile flow 96
Slide 91-

PS = portal space with portal vein hepatic artery bile canaliculus lyphatic vessel CV= central vein 96
Slide 92-

liver lobule portal lobule (defined by bile flow) hepatic acinus (defined by blood flow) 96
Slide 93-

HV = hepatic venule Hepatic acinus 96
Slide 94-

Functions of the liver • Energy metabolism and substrate interconversion • Synthetic function • Transport and storage function • Protective and clearance function
Slide 95-

Bile secretion = digestive/absorptive function of the liver Components of bile • bile salts (conjugates of bile acids) • bile pigments (e.g. bilirubin) • cholesterol • phospholipids (lecithins) • proteins • electrolytes (similar to plasma, isotonic with plasma) 600-1200 ml/day
Slide 96-

Function of bile • bile salts (conjugates of bile acids with taurine or glycine) important for absorption of lipids in small intestine. Bile acids emulsify lipids and form mixed micelles necessary for lipid absorption. • bile acids are derived from cholesterol and therefore are responsible for excretion of cholesterol. • excretion of bilirubin (product of hemoglobin degradation). • bile acids are actively absorbed and recirculated through enterohepatic circulation.
Slide 97-

enterohepatic circulation of bile 73
Slide 98-

74 Mechanism of uptake and secretion of bile acids by hepatocytes ATP
Slide 99-

Intestinal secretion: 1500 ml/day. Composition: • mucus • electrolytes • water
Slide 100-

degradation of structurally complex foodstuffs by digestive enzymes 3 categories of energy-rich foodstuffs: carbohydrates, proteins and lipids DIGESTION absorbable units as a result of the digestive process are transported along with water, vitamins and electrolytes from the lumen of the GI tract into the blood and lymph ABSORPTION
Slide 101-

Digestion chemical degradation of nutrient macromolecules by digestive enzymes • Luminal disgestion: enzymes secreted into the lumen of GI tract from salivary glands, stomach and pancreas • Membrane or contact digestion : hydrolytic enzymes synthesized by enterocytes and inserted into the brush border membranes. Integral part of the microvillar membrane in close vicinity of specific carrier proteins (= digestion-absorption coupling) • cytoplasmic disgestion: digestive enzymes in the cytoplasm (peptidases)
Slide 102-

Sites of absorption 78
Slide 103-

ppt slide no 103 content not found
Slide 104-

79
Slide 105-

Average daily.... • intake: ~ 2 liters • loss through GI tract: 100 ml (only 5% of intake) through feces • GI secretion: 7 liters • water absorption by GI tract: 9 liters 80
Slide 106-

Mechanism of water absorption: standing osmotic gradient hypothesis Absorption of water is passive and is determined by differences in osmolarity of luminal content and blood, therefore net transport of water can occur in both direction.
Slide 107-

1. Active Na+ pumping (Na/K ATPase) into lateral intercellular space 2. passive entry of Cl- into lateral intercellular space 3. establish osmotic gradient in lateral space 4. entry of water by osmosis into lateral space 5. hydrostatic flow of water Standing gradient osmosis: 81
Slide 108-

Tight junctions: transcellular vs. paracellular transport Tight junctions connect epithelial cells of the GI tract. Tight junctions are leaky (the most in the duodenum) for water and ions. Transmucosal transport of water and ions can occur through tight junctions and lateral intercellular space (paracellular transport = 2) or through epithelial cells (transcellular transport = 1) 79
Slide 109-

Digestion and absorption of carbohydrates
Slide 110-

Diet contains • digestible carbohydrates • monosaccharides: glucose, fructose, sorbitol, (galactose in form of milk lactose = galactose+glucose) • disaccharides: sucrose, lactose, maltose • oligosaccharides/polysaccharides: starch (made of amylose and amylopectin), dextrins, glycogen • non-digestible carbohydrates dietary fibers, mainly cellulose (ß-1,4 linked glucose polymer; humans lack enzyme to hydrolyse ß-1,4 bonds). Fibers are extremely important for regular bowel movements.
Slide 111-

Digestive enzymes break down oligosaccharides and polysaccharides into the 3 absorbable monosaccharides • glucose • fructose • galactose
Slide 112-

Digestive enzymes for carbohydrate digestion • luminal digestive enzymes • brushborder enzymes
Slide 113-

Luminal digestive enzymes for carbohydrate digestion: salivary and pancreatic amylase: cleaves the -1,4 glycosidic bond of amylose and amylopectin (starch and glycogen) to produce maltose, maltotriose and -limit dextrins. Note:  -amylase cannot hydrolyze  -1,6 and terminal  -1,4 glycosidic bonds. 87
Slide 114-

Brush border enzymes digest disaccharides and oligosaccharides
Slide 115-

Digestion-absorption coupling 88 G2 G3
Slide 116-

Absorption mechanism of monosaccharides Digestion by brush border enzymes occurs in close vicinity to monosaccharide transporters. • Glucose and galactose: SGLT1 absorption via a secondary active (uphill), Na-dependent transport • Fructose: GLUT5 absorption by facilitated (carrier mediated), Na-independent mechanism 90
Slide 117-

Digestion and absorption of lipids
Slide 118-

Lipids in the GI tract: • exogenous (diet: triglycerides (90%), phospholipids, sterols (e.g. cholesterol), sterol esters) • endogenous (bile, desquamated intestinal epithelial cells)
Slide 119-

Digestion of lipids Most of the lipids are digested in the small intestine, but also in stomach. Enzymes for lipid digestion • lingual lipase (from salivary secretion; break down of mainly medium-chain triglycerides as abundant in milk; optimal pH = 4 --> lipid digestion in the stomach) • gastric lipase (secreted by chief cells) • pancreatic lipase = glycerol ester hydrolase (triglycerides) • pancreatic phospholipase A2 (phospholipids) • pancreatic cholesterol esterase (cholesterol ester).
Slide 120-

91
Slide 121-

Mechanism of lipid absorption • The intestinal villi are coated by an unstirred water layer which reduces the absorption of the poorly water soluble lipids.
Slide 122-

• Emulsification: In the small intestine lipids are emulsified by bile acids (i.e. formation of small droplets of lipids coated with bile acids). Bile salts (bile salts = conjugation of bile acids with taurine or glycine) are polar and water soluble, and function as detergents. Emulsion droplets allow access of the water-soluble lipolytic enzymes by increasing surface area. 92
Slide 123-

• Micelle formation and lipid absorption: - At a certain concentration (critical micellar concentration) bile salts aggregate into micelles that incorporate lipid digestion products. Lipids become water soluble by micellar solubilization. - Lipids diffuse across the unstirred water layer as micelles and are mostly absorbed passively (diffusion) by enterocytes (mainly in the jejunum). - Absorption is enhanced by Na+-dependent long-chain fatty acid transport protein (MVM-FABP=microvillous membrane fatty acid-binding protein) and cholesterol transport protein in the brush border membrane (secondary active and facilitated transport).
Slide 124-

• In the enterocytes lipids are bound by cytosolic lipid transport proteins and transported to the smooth endoplasmic reticulum. There triglycerides are reassembled from fatty acids and monoglycerides • Triglycerides together with lecithin, cholesterol and cholesterol ester, are packaged into lipoproteins to form water-soluble chylomicrons (lipid aggregates). • Transport of lipids to the lymphatic vessels by exocytosis. Additionally, mainly medium-chain and short-chain fatty acids directly reach the blood stream and are transported bound to serum albumin.
Slide 125-

Lipid digestion & absorption 94
Slide 126-

• Absorption of bile acids. Bile acids are absorbed in the terminal ileum by Na+-dependent secondary active transport (mainly conjugated bile acids) and by diffusion (mainly unconjugated bile acids). Bile acids are recirculated to the liver via portal circulation and extracted from portal blood for reuse. 93
Slide 127-

Digestion and absorption of proteins
Slide 128-

Proteolytic digestive enzymes • gastric secretion (G) • pancreatic secretion (P) • brush border enzymes (BB) • cytoplasmic (C)
Slide 129-

• Endopeptidase: hydrolyzes internal peptide bonds: • trypsin (P) • chymotrypsin (P) • elastase (P) • pepsin (G) • Exopeptidase: hydrolyzes external peptide bonds: • carboxypeptidase A (P) • carboxypeptidase B (P) • aminopeptidase (P, BB, C) P = pancreas, BB = brush border, C = cytoplasm
Slide 130-

Protein digestion >> Gastric proteolysis: pepsin is activated by low pH from proenzyme pepsinogen and acts as endopeptidase. >> Small intestine: major site of protein digestion. • Luminal protein digestion: Pancreatic proteases are secreted as inactive proenzymes. Chyme in the duodenum stimulates the release of enterokinase (= enteropeptidase) which converts trypsinogen into trypsin (active form). Trypsin itself converts the other proenzymes to active enzymes. Luminal protein digestions produces single amino acids and small peptides (dipeptides, tripeptides and tetrapeptides) • Brush border peptidases are integral membrane proteins produce single amino acids and smaller peptides from tetrapeptides and larger peptides. • Intracellular cytoplasmic peptidases break down dipeptides and tripeptides into single amino acids.
Slide 131-

Protein absorption: Products of protein digestion are absorbed as • amino acids: 7 amino acid transporters in brush border membrane (B&L, table 39-2): - 5 Na-dependent (absorption occurs via secondary active process by carrier that are energetically coupled to the Na+ concentration gradient across the brush border membrane of intestinal epithelial cells) - 2 Na-independent (facilitated transport). • peptides: di- and tripeptides by peptide transporters. (• proteins: in the newborn of some animal species absorption of immunoglobulins provides an important form of passive immunity).
Slide 132-

Amino acid transport across the basolateral membrane • 5 classes of amino acid transporter at the basolateral membrane (B&L, table 39-3) - 2 Na-dependent - 3 Na-independent • Amino acids are transported in the portal blood
Slide 133-

protein digestion & absorption 95
Slide 134-

Absorption of vitamins
Slide 135-

Vitamins: organic substances needed in small quantities for normal metabolic function, growth and maintenance of the body. • Fat-soluble vitamins: Vitamins A, D, E and K • Water-soluble vitamins: Vitamins B1, B2, B6, B12, niacin, biotin and folic acid
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• Water-soluble vitamins (cont.): Absorption of Vitamin B12 • Vitamin B12 (cobalamin) is bound to a cobalamin binding protein (intrinsic factor) secreted by the parietal cells of the stomach. • The Vitamin B12-intrinsic factor complex is absorbed in the terminal ileum. • Transport in the blood of Vitamin B12 by binding to the protein transcobalamin. • Vitamin B12 is stored in the liver.
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