Gastrointestinal System PDF

10 Gastrointestinal System myenteric or Auerbach’s plexus: this lies between the FUNCTIONS circular and longitudinal muscle layers; it is mainly The functions...

10 Gastrointestinal System myenteric or Auerbach’s plexus: this lies between the FUNCTIONS circular and longitudinal muscle layers; it is mainly The functions of the various components of the gastroin- involved in motor function testinal (GI) system are: submucosal or Meissner’s plexus: this lies within the Oral cavity: teeth crush and tear food; the tongue forms submucosa; it is mainly sensory. a food bolus in preparation for swallowing; saliva secre- The enteric nervous system responds to numerous tion initiates carbohydrate digestion. gut transmitters such as cholecystokinin, substance P, Pharynx and oesophagus: conveys food from the oral vasoactive intestinal peptide (VIP) and somatostatin; cavity to the stomach. it is responsible for the majority of gut secretion and Stomach: stores food; mechanically and chemically motility. digests food; regulates the passage of chyme into the The enteric nervous system also receives input from the duodenum; secretes intrinsic factor. autonomic (extrinsic) nervous system: Small bowel: food passes from the stomach into the Sympathetic: fibres terminate in the submucosal and small intestine; this is where the majority of food diges- myenteric plexuses; stimulation of the sympathetic tion and absorption occurs. system leads to: Large bowel: water is removed from undigested food, blood vessels: vasoconstriction which is then stored in the rectum in preparation to be glandular tissue: inhibits secretion excreted; vitamin K and some B vitamins are produced sphincters: contraction by resident bacterial flora. circular muscle of bowel: inhibits (↓ motility). Liver: an important site for carbohydrate, protein and Parasympathetic: fibres terminate in the myenteric lipid metabolism; involved in the synthesis of several plexus only; stimulation of the parasympathetic sys- plasma proteins and clotting factors; the primary site tem leads to: for detoxification and elimination of body waste and glandular tissue: increases secretion toxins. sphincters: relaxation Gall bladder: stores and concentrates bile. circular muscle of bowel: stimulates (↑ motility). Pancreas: has both exocrine and endocrine functions, secreting the majority of digestive enzymes. Hormones and Neurotransmitters Play an important role in regulating GI motility and Nervous and Hormonal Regulation secretion; these include: gastrin Within the GI Tract secretin Nervous Regulation cholecystokinin (CCK) The nervous system of the GI tract consists of: pancreatic polypeptide Intrinsic or enteric system. gastric inhibitory polypeptide (GIP) Extrinsic system: motilin sympathetic enteroglucagons parasympathetic. neurotensin. The intrinsic nervous system is found in the wall of the These hormones and neurotransmitters will be dis- GI tract and forms two well-defined plexuses: cussed individually in the relevant sections. 214 WWW.BOOKBAZ.IR  CHAPTER 10 Gastrointestinal System 215 Parasympathetic impulses via cranial nerves VII and IX Oral Cavity, Pharynx and Oesophagus stimulate saliva secretion; sympathetic impulses lead to Chewing vasoconstriction and a decrease in saliva secretion. Food is ingested through the mouth and is divided between two regions: Swallowing vestibule: space between the teeth, lips and cheeks Swallowing can be divided into a number of phases: oral cavity: inner area bound by the teeth. Oral phase: voluntary; a food bolus is pushed against Chewing or mastication has a number of functions: the roof of the mouth by the tongue; this forces the food teeth are able to cut, grind and tear food, allowing it into the oropharynx and then into the pharynx. to be swallowed more easily Pharyngeal phase: involuntary; the superior constric- mixes food with saliva and mucus; this lubricates it tor raises the soft palate (preventing food entering the in preparation for swallowing, and starts carbohy- nasopharynx). In addition it initiates a wave of con- drate digestion with salivary amylase. traction (peristalsis) that pushes the food through the upper oesophageal sphincter. At this stage respiration is Saliva inhibited so as to prevent food entering the respiratory Saliva is secreted by a number of glands: system. parotid: watery secretion lacking mucus; accounts Oesophageal phase: the wave of contraction, which was for around 25% of saliva secretion; also contains sali- initiated by the superior constrictor in the pharynx, vary amylase and IgA continues into the oesophagus. This wave of contraction submandibular: produces a more viscous saliva propels the food into the stomach. If the food fails to (a mixed serous and mucosal saliva); accounts for enter the stomach then the resulting distension initiates approximately 70% of saliva secretion a secondary peristaltic wave. sublingual: contains mucoproteins; accounts for only 5% of saliva secretion. Oesophageal Sphincter Numerous saliva glands are present over the tongue and The oesophageal sphincter is an area of high pressure palate. (15–25 mmHg) in the region 2 cm above and 2 cm below Saliva has a number of functions: the diaphragm; it is a physiological sphincter as there are lubrication to help swallowing: mucus no anatomical differences to identify it as the sphincter. speech The oesophageal sphincter acts to prevent gastric juices taste refluxing from the stomach into the oesophagus. antibacterial action: lysozyme and IgA In addition to the physiological sphincter there are a starch digestion: amylase. number of other factors that assist in preventing reflux: Formation of saliva within the salivary glands is a two- the right crus of the diaphragm compresses the oeso­ stage process: phagus as it passes through the oesophageal hiatus 1. Isotonic fluid of similar composition to the extracellular the acute angle at which the oesophagus enters the fluid (ECF) is secreted by the acinar component of the stomach acts as a valve salivary gland. mucosal folds in the lower oesophagus act as a valve 2. The isotonic fluid is modified as it moves along the duct; closure of the sphincter is under vagal control; how- Na+ and Cl− is removed and K+ and HCO3− are added by ever, the hormone gastrin causes the sphincter to means of ATP transport proteins. contract (secretin, CCK and glucagon cause it to During low rates of secretion the saliva is dilute as there relax). is plenty of time for ductal modification. During high rates of secretion the Na+, HCO3− and Cl− STOMACH content increases and is thus more concentrated. Control of the secretion of saliva is via the autonomic Gastric Mucosa nervous system; this reflex is stimulated by the salivary nuclei in the medulla; secretion of saliva is stimulated by: The gastric mucosa contains a variety of secretory cells; stimulation of mechanoreceptors and chemorecep- the mucosa is divided into: tors in the mouth columnar epithelium: secretes a protective mucus layer higher centres in the CNS, i.e. smelling or thinking gastric glands: intersperse the mucosa; they contain about food. a variety of secretory cells. 216 SECTION II Physiology These secretory cells include: Stomach acid has a pH of around 1–3; it plays a number mucus cells: secrete mucus and are situated at the of roles: opening of the gastric gland tissue breakdown peptic or chief cells: found at the base of the gastric converts pepsinogen to the active pepsin glands and secrete pepsinogen forms soluble salts with calcium and iron; this aids parietal or oxyntic cells: secrete hydrochloric acid their absorption and intrinsic factor acts as an immune defence mechanism by killing neuroendocrine cells: secrete a number of peptides micro-organisms. that regulate GI motility and secretion, i.e. gastrin. Gastric acid is secreted by the parietal cells; when acti- The predominant cell type in the gastric glands varies vated, deep clefts form in the apical membrane; these throughout the various regions of the stomach: canaliculi allow the acid to be secreted into the stomach. fundus and body: peptic and parietal cells predominate Chloride and hydrogen ions are pumped from the pari- antrum and pylorus: parietal cells are less common; etal cells; this process is energy dependent. mucus and neuroendocrine (secreting gastrin) cells H+ ions are pumped from the cell by the H+/K+ ATPase predominate system. cardia: gastric glands are composed almost com- Cl− ions are pumped from the cell by two routes: one is a pletely of mucus cells. chloride channel, the other is a Cl−/K+ co-transport sys- tem (K+ is thus cycled into the cell via the H+/K+ ATPase system and out via the Cl−/K+ system). Gastric Secretion H+ ions are produced by oxidative processes; this also Gastric Acid (Fig. 10.1) produces a hydroxyl ion; in a reaction catalysed by car- The stomach secretes approximately 2–3 L/day; it bonic anhydrase this results in the formation of HCO3−, contains: which is then exchanged for Cl− on the basolateral sur- hydrochloric acid face of the cell. pepsinogen The secretion of HCO3− is a protective mechanism that mucus prevents the gastric acid from damaging the mucosa; intrinsic factor it is referred to as the ‘alkaline tide’; the production of salt and water. HCO3− can be influenced by prostaglandins. + G-cell Entero- D-cell + chromaffin cells + ACh Gastrin + Somatostatin + + Histamine + – Parietal cell H+ – K+ – – Secretin CCK Duodenal GIP mucosa Fig. 10.1 Regulation of acid secretion by the parietal cell. (From McGeown JG. Physiology, 2nd edn. Churchill Livingstone, Edinburgh, 2002, with permission.) WWW.BOOKBAZ.IR  CHAPTER 10 Gastrointestinal System 217 Pepsinogen Secretion accounts for around 60% of gastric secretion. Distension The peptic cells produce pepsinogen, a proteolytic of the stomach and the chemical composition of food enzyme that hydrolyses peptide bonds in proteins. lead to acetylcholine release from the vagus. The enzyme is secreted into the gastric glands in an Intestinal phase: only accounts for 5% of gastric secre- inactive form (pepsinogen); exposure to the acid envi- tion; the stimulation is the presence of food in the duo- ronment in the stomach activates the enzyme (pepsin). denum; this results in the release of gastrin from G-cells in the duodenal mucosa. Mucus Secretion There are a number of other influences on gastric secretion: Mucus is secreted from cells at the neck of the gastric the secretion of gastrin is inhibited when the pH falls glands; the secreted mucus forms a layer (mucosal barrier) to around 2–3 over the gastric epithelium and prevents the gastric acid somatostatin secreted from neuroendocrine cells and secreted pepsins from digesting the stomach lining. (D-cells) inhibits gastrin secretion The mucus is alkaline; this helps to neutralize gastric acid. secretin from the duodenal mucosa is released in Additional factors which protect the stomach from response to acid in the duodenum; it inhibits gastrin digestion include: release tight epithelial junctions prevent acid reaching deeper fatty food in the duodenum leads to the release of tissues CCK and GIP; both inhibit gastrin secretion. prostaglandin E secretion has a protective role by The action of hormones released in the duodenum is increasing the thickness of the mucus layer, stimulat- referred to as the enterogastric reflex. ing HCO3− production and increasing blood flow in the mucosa (bringing nutrients to any damaged areas). Gastric Motility The main functions of the stomach are storage and mix- Intrinsic Factor Secretion ing and propulsion of food into the intestine; the storage Secreted from parietal cells; the stimulus for excretion is area consists of the fundus and body, whereas the mix- the same as for acid secretion. ing and propulsion area is the antrum and pylorus. Intrinsic factor (IF) binds to vitamin B12; it is then absorbed in complex with the IF via specialized recep- Storage tors in the ileum (see below). The stomach has a resting volume of around 50 mL and an intragastric pressure of 5–6 mmHg; however, it is Regulation of Gastric Secretion able to accommodate significantly greater volumes with Divided into three phases: little change in pressure (approximately 1 L). As the cephalic stomach is distended, parasympathetic input from the gastric vagus inhibits muscle contraction. intestinal. Cephalic phase: sight, smell and even the anticipation Mixing and Propulsion of food lead to impulses from the appetite centre in the The stomach has three muscle layers: longitudinal, cir- hypothalamus to the stomach; it contributes to almost cular and oblique. 30% of gastric secretions. This descending input is para- Contractions in the stomach are more intense in the sympathetic and runs in the vagus; vagal activity stimu- more muscular pyloric area in comparison with the lates gastric secretion in a number of ways: gentle contractions in the storage area of the fundus. direct stimulation of the gastric glands via acetylcho- Peristaltic waves push food or chyme towards the pylorus; line release as pressure increases the pyloric sphincter will open and a release of gastrin from the neuroendocrine cells small amount of food is allowed through to the duodenum. (G-cells) in the antrum; gastrin stimulates acid and Parasympathetic impulses tend to increase motility pepsin secretion whereas sympathetic impulses decrease motility. release of histamine from mast cells; this stimu- The amount of food allowed in to the duodenum is care- lates parietal cells via H2 receptors, which leads to fully regulated by a number of factors: acid production (gastrin also stimulates histamine gastric volume:↑volume then more rapid emptying release). fatty food: CCK and GIP are released by the small Gastric phase: food entering the stomach stimulates the intestine in response to fatty foods; they increase gastric phase; this is the primary stimulus to secretion and contractility of the pyloric sphincter 218 SECTION II Physiology proteins: proteins and amino acids stimulate gastrin There are three groups of drugs used in the reduction of release; gastrin increases contractility of the pyloric acid secretion: sphincter histamine (H2-receptor) antagonists, e.g. cimeti- acid: acid entering the duodenum results in a vagally dine and ranitidine: these drugs act by blocking mediated delay in gastric emptying and also leads to H2-receptors on parietal cells. Although these cells secretin release. Secretin inhibits antral contractions also possess gastrin and muscarinic receptors, both and increases contractility in the pyloric sphincter. gastrin and acetylcholine mainly stimulate acid pro- Secretin also stimulates HCO3− release from the pan- duction indirectly by stimulating histamine release. creas to neutralize the acid The blocking of H-receptors prevents the intracellu- hypertonic chyme: delays gastric emptying. lar increase in cAMP, and thus acid production muscarinic antagonists, i.e. pirenzepine: this is only of historical value, as this drug is no longer in clinical Clinical Physiology use. Pirenzepine was a selective M1-receptor antago- Vomiting nist that was selective for the muscarinic receptors The reflex action of ejecting the contents of the stomach on parietal cells but did not produce the unwanted through the mouth. symptoms of blurred vision, dry mouth, etc. Prior to vomiting, autonomic symptoms such as saliva- proton pump inhibitors (PPIs), e.g. omeprazole: this tion, pallor, sweating and dizziness often occur. group of drugs acts directly on the proton pump The events which occur during vomiting are: (H+/K+ ATPase). It is inactive at neutral pH but is respiration is inhibited activated by the acidic conditions in the stomach; the larynx closes and the soft palate rises it then irreversibly binds to sulfydryl groups on the the stomach and pyloric sphincter relax and the duo- proton pump. denum contracts, propelling intestinal contents into The mucosal protectants aim to support the mucus the stomach layer that normally protects the gastric mucosa; there the diaphragm and abdominal wall contracts → are three types: intragastric pressure rises sucralfate: formed from sulphated sucrose and alu- the gastro-oesophageal sphincter relaxes and the minium hydroxide, it polymerizes at pH < 4 to form pylorus closes a sticky layer that adheres to the base of the ulcer stomach contents expelled through the mouth. bismuth chelate: acts in a similar manner to sucral- The vomiting reflex is co-ordinated by the vomiting fate; in addition it has been shown to eradicate centre in the medulla; stimulation of the vomiting cen- Helicobacter pylori tre leads to motor impulses passing along cranial nerves misoprostol: a synthetic analogue of prostaglandin V, VII, IX and XII, and to the intercostals and abdomi- E2. This prostaglandin is thought to protect gastric nal muscles and diaphragm. mucosa by stimulating the secretion of mucus and Causes of vomiting include: bicarbonate, and increasing the mucosal blood flow. stimulation of the posterior oropharynx Antacids are a very simple treatment for peptic ulcers, excessive distension of the stomach or duodenum and simply consist of alkaline substances that increase stimulation of the labyrinth, e.g. motion sickness the pH within the stomach; examples include: severe pain sodium bicarbonate raised intracranial pressure magnesium hydroxide and magnesium trisilicate stimulation of the chemoreceptor trigger zone by aluminium hydroxide. noxious chemicals Surgical treatment bacterial irritation of the upper GI tract. With the advent of PPIs surgical treatment has become much less common. Indications include: Treatment of Peptic Ulceration chronic unhealed ulcer The treatment of peptic ulcer disease can be divided into failure to heal after more than two courses of treatment medical and surgical. possible malignancy Medical treatment complications, i.e. bleeding, perforation. The choices for medical treatment are: The options for surgical treatment include (Fig. 10.2): reduce acid secretion Bilroth I partial gastrectomy mucosal protection Bilroth II partial gastrectomy antacids (pH increasers). truncal vagotomy and gastrojejunostomy WWW.BOOKBAZ.IR  CHAPTER 10 Gastrointestinal System 219 Upper 1/3 Upper 1/3 stomach stomach Duodenum Duodenum A B Gastrojejunostomy Pyloroplasty C D E F Fig. 10.2 Surgical options for peptic ulceration. (A) Bilroth I. (B) Bilroth II or Polya. (C) Truncal vagotomy and gastrojejunostomy. (D)Truncal vagotomy and pyloroplasty. (E) Selective vagotomy and pyloroplasty. (F) Highly selective vagotomy (no drainage procedure needed). (From McGeown JG. Physiology, 2nd edn. Churchill Livingstone, Edinburgh, 2002, with permission.) 220 SECTION II Physiology truncal vagotomy and pyloroplasty large surface area selective vagotomy and pyloroplasty circular folds called plicae circulares, which cause highly selective vagotomy (no drainage procedure the chyme to spiral round, and thus increase the time needed). for absorption to take place The surgical treatment of peptic ulcers is associated the circular folds are covered with villi—finger-like with a number of complications. These can be divided projections approximately 1 mm high; each of these into post-gastrectomy syndromes and those that occur villi is further covered with microvilli (‘brush-border’). post-vagotomy. These serve to further increase the surface area. Post-gastrectomy syndromes Interspersed among the villi are the crypts of Lieber­kuhn. Malnutrition: occurs due to small capacity stomach, These are analogous to the gastric glands and contain rapid gastric emptying and rapid intestinal transit. a number of different cell types: Deficiency: undifferentiated cells that constantly replace iron deficiency, as it is in the wrong ionic state for entero­cytes absorption D-cells: produce somatostatin vitamin B12 deficiency, due to a lack of intrinsic factor. S-cells: produce secretin Dumping syndromes: these can be early or late. Early N-cells: produce neurotensin dumping occurs 30–45 min after eating and is due to Enterochromaffin cells: produce 5-hydroxytryptamine. rapid gastric emptying of a hyperosmolar meal into the The ‘brush-border’ secretes a number of enzymes small bowel; this results in fluid moving into the small involved in digestion: bowel by osmosis (third space loss) and results in diz- disaccharidases: maltase, sucrase ziness, weakness and palpitations. Late dumping is due peptidases to rapid swings in insulin secretion in response to the phosphatases glucose load in the small bowel; this leads to rebound enteropeptidase or enterokinase (activates pancre- hypoglycaemia. atic trypsinogen) Diarrhoea: due to early gastric emptying and passage of lactase (under 4 years). hyperosmolar chyme attracting fluid into the bowel. The duodenum contains Brunner's glands, which secrete Bilious vomiting: the loss of the pylorus allows reflux of mucus rich in bicarbonate (they are not present in the duodenal contents; this leads to bilious vomiting. The jejunum or ileum). refluxed bile can also lead to gastritis and further ulcer development. Absorption (Table 10.1) Infection: there is a decreased ability to destroy bacteria, The small intestine secretes 2–3 L/day of isotonic fluid; particularly tuberculosis. Cl− is transported to the bowel lumen and Na+ and water Carcinoma: the duodenal reflux increases the risk of follow. In addition, the bowel secretes a number of hor- developing gastric cancer in the gastric remnant. mones (see above) and enzymes (see Pancreas section). Effects of vagotomy The absorption of nutrients in the small bowel can be Reduced gastric acid secretion. divided into: Delayed gastric emptying. carbohydrates Failure of the pylorus to relax prior to gastric peristaltic fats wave. proteins Reduced pancreatic exocrine secretions. fluids and electrolytes Diarrhoea secondary to loss of vagal control of the small vitamins bowel. iron Increased risk of large bowel cancer due to excessive bile calcium. salts reaching the colon. Carbohydrates (Fig. 10.3) Glucose and galactose are absorbed via a Na+-dependent pro- SMALL INTESTINE cess in which a Na+/K+ ATPase pumps out Na+. The glucose/ galactose are then absorbed with the Na+ via a cotransport Small Intestine Mucosa protein. A Na+-independent process absorbs fructose. The primary function of the small bowel is the absorp- tion of nutrients; a number of characteristics make it Fats (Fig. 10.4) particularly suited to this role: The absorption of fats is a complex multistage process: WWW.BOOKBAZ.IR  CHAPTER 10 Gastrointestinal System 221 TABLE 10.1 Summary of the Absorption Micelles and Secretion of Fluid Within the GI Tract Secreted/ Monoglycerides Absorbed Ingested Fatty acids Mouth Nothing 2–3 L fluid ingested 1.5 L saliva secreted Stomach Lipid-soluble 2–3 L gastric compounds, juices secreted Triglycerides e.g. alcohol Gallbladder Absorbs water and 500 mL bile Chylomicrons concentrates bile secreted Pancreas Nothing 1.5 L pancreatic juices secreted Lacteals Small bowel 8–9 L fluid 1.5 L intestinal absorbed secretions Fig. 10.4 Lipids are absorbed by diffusion as mono- Large bowel 1 L of fluid 100 mL excreted glycerides and fatty acids. Inside the cell they are absorbed in faeces reconstituted to triglycerides, packaged as chylomi- crons, and then enter the lymphatic channels (lacteals). (From McGeown JG. Physiology, 2nd edn. Churchill A Secondary active B ‘Facilitated’ Livingstone, Edinburgh, 2002, with permission.) transport diffusion Glucose Na+ Galactose Fructose fats form globules in the stomach globules are coated with bile salts in the duodenum the bile salts disperse these globules into smaller drop- lets; this increases the surface area exposed to pancre- Primary active transport atic enzymes Na+ fatty droplets are broken down by pancreatic lipases to ATP monoglycerides and free fatty acids (FFA) K+ the monoglycerides and FFAs combine with bile salts to Glucose Galactose Fructose form micelles micelles have a hydrophilic outer layer and are able to diffuse into the enterocytes; the bile salt stays in the Capillary Capillary bowel lumen in the enterocytes, the smooth endoplasmic reticulum reforms triglycerides from the absorbed monoglycer- Key ides and FFAs Movement against concentration gradient the reformed triglycerides are formed into particles of Diffusion down concentration gradient fat called chylomicrons, which are released from the basal layer of the enterocyte to diffuse into the lacteals Carrier molecule within the villi; from here they enter the lymphatic cir- ATP ATP dependent pump culation and then into the venous circulation. Fig. 10.3 Carbohydrate absorption mechanism. (A) Protein (Fig. 10.5) Glucose and galactose are absorbed by an active trans- Proteins are broken down into amino acids by the pro- port mechanism using Na+ as a cotransport. (B) Fructose teolytic enzymes released from the stomach (pepsin) absorption is passive, but utilizes a carrier molecule. and pancreas (see below). (From McGeown JG. Physiology, 2nd edn. Churchill A Na+-dependent cotransport mechanism absorbs amino Livingstone, Edinburgh, 2002, with permission.) acids. 222 SECTION II Physiology Amino Water-soluble vitamins (C and B) are absorbed by more + acid Secondary active Na specific mechanisms: transport vitamin C is absorbed by a Na+-dependent mecha- nism in the jejunum vitamin B12 is absorbed in the ileum after intrinsic Primary active factor (secreted in the stomach) binds to its specific transport receptor. The IF–vitamin B12 complex is then taken Na + up into the cell ATP the remaining B vitamins diffuse freely across the + enterocyte cell membrane. K Amino acid Iron Iron is absorbed in the duodenum and jejunum in the ferrous (Fe2+) and not the ferric (Fe3+) form; gastric acid Capillary is responsible for converting iron to the ferrous form. Absorption is then via the transport protein transferrin. Fig. 10.5 Amino acids are absorbed using a Na+ This binds iron and links to a membrane-bound recep- cotransport system. (From McGeown JG. Physiology, tor, and is then taken into the cell via endocytosis; it 2nd edn. Churchill Livingstone, Edinburgh, 2002, with is then transferred to the plasma and binds to plasma permission.) transferrin. Calcium There are four transporters: neutral amino acids Absorption is dependent on a calcium-binding protein basic amino acids in intestinal cells; these receptors can be increased by acidic amino acids vitamin D, and thus the rate of calcium absorption can proline and hydroxyproline. be increased when plasma levels fall. The majority of amino acids are absorbed in the upper small intestine; any that enter the large bowel are metab- Small Intestinal Motility olized by the resident bacterial flora. There are three types of movement in the small bowel: segmentation (feeding) Fluids and Electrolytes peristalsis (feeding) Approximately 2–3 L of fluid is ingested each day; migrating motility complex (MMC) (fasting). another 8–9 L is secreted into the GI tract, but only Segmentation is a movement that facilitates mixing of 100–200 mL is excreted in the faeces. chyme; the circular muscle layer contracts and relaxes Na+ absorption is coupled with the absorption of glu- in adjacent segments; this results in circular movements cose and amino acids; active absorption is stimulated of the chyme. by aldosterone. Peristalsis is a propulsion movement that is triggered by K+ is absorbed along a concentration gradient (caused distension. The longitudinal muscle contracts; midway by water absorption); a small amount is secreted in through contraction of the longitudinal muscle the cir- mucus. cular muscle also contracts. This pattern of contraction Anions such as Cl− are generally absorbed by electro- is repeated and moves food through the bowel. chemical gradients created by Na+ absorption. Peristaltic contractions eventually reach the ileocaecal The absorption of water is a result of the osmotic gra- valve and cause it to relax, thus allowing food to enter dient established by the absorption of nutrients and the large bowel. electrolytes. Peristaltic contractions last a few seconds and only propel the food a few centimetres; the MMC leads to Vitamins contraction along the full length of the small bowel and Vitamins are divided into fat-soluble and water-soluble; lasts several hours. Their purpose is to push any remain- this classification refers to the method of absorption. ing food debris into the colon. The stimulation for the Fat-soluble vitamins (A, D, E and K) are absorbed MMC is not fully understood, but may involve the hor- within the micelles created during fat absorption. mone motilin. WWW.BOOKBAZ.IR  CHAPTER 10 Gastrointestinal System 223 The movements of segmentation and peristalsis are PANCREAS intrinsic and result from the basal electrical rhythm in the intestine. It can be influenced by extrinsic nervous Exocrine Secretions input: Fluid Component parasympathetic: increases rate of contraction The pancreas secretes approximately 1.5 L of fluid per day; sympathetic: decreases rate of contraction. it contains a variety of enzymes and is rich in bicarbonate. In addition to the autonomic input, there are several The epithelial cells that line the ducts form the fluid reflexes which also influence intestinal contractility: component of pancreatic juice; HCO3− is transported ileogastric reflex: distension of the ileum decreases into the lumen in exchange for Cl− and directly via a gastric motility luminal channel. Sodium and potassium are exchanged gastroileal reflex: increase in gastric secretion or con- for H+ formed by the reaction catalysed by carbonic tractility increases ileal motility. anhydrase. Na+ follows HCO3− to maintain electro- chemical neutrality and water follows by the osmotic Clinical Physiology gradient created by the movement of Na+ and HCO3−. Physiological Effects of Duodenal Resection Enzyme Component Removal of the duodenum (duodenectomy) leads to a The enzymes secreted by the pancreas can be divided into: range of physiological abnormalities, including: proteolytic Ulceration of small bowel: the duodenum is able to amylase withstand gastric acid better than small bowel; this is lipolytic. due to HCO3− secreted from the Brunner's glands and Proteolytic enzymes from the pancreas—allowing the neutralization of gas- These enzymes are secreted in an inactive form, called tric acid within the chyme. Following duodenal resec- zymogen granules, from pancreatic acinar cells. The key tion, surgical reconstruction of bowel continuity often event in the activation of these enzymes is activation of involves small bowel; the rerouted gastric acid causes trypsinogen to trypsin. Activation of trypsinogen is by peptic ulceration in the small bowel. an enzyme secreted by the duodenum (enterokinase) Malabsorption: Fe2+, Ca2+ and PO4− malabsorption and and the alkaline environment. impaired fat emulsification. Trypsin then activates the other enzymes: Dumping: loss of control over gastric emptying leads chymotrypsinogen: chymotrypsin (cleaves peptide to uncontrolled passage of chyme into the small bowel, bonds) resulting in dumping. proelastase: elastase (cleaves peptide bonds) trypsinogen: trypsin (cleaves peptide bonds) Physiological Effects of Terminal Ileal Resection procarboxypeptidase: carboxypeptidase (cleaves pep- Removal of the terminal ileum (ilectomy) leads to a range tides at the C-terminus). of physiological abnormalities, including: Amylase Bile salt reabsorption: the terminal ileum is the site of Responsible for the majority of starch digestion; it splits bile salt absorption; loss of this mechanism leads to: α-1,4-glycosidic bonds; the brush-border enzymes of the small bowel digest the resulting oligosaccharides. bile salts in the colon; this alters the bacterial flora Lipolytic enzymes and stool consistency, and can lead to an increased As with proteolytic enzymes, the lipolytic enzymes are risk of colonic malignancy excreted in an inactive form; they are all activated by due to the loss of enterohepatic circulation, there is a trypsin. These enzymes include: decrease in bile salt pool; this predisposes to choles- lipase: cleaves triglycerides to FFAs and glycerol terol gallstones. co-lipase: helps bind lipase to the lipids Vitamin B12 deficiency: receptor-mediated reabsorp- phospholipase A2: cleaves FFAs from phospholipids tion in conjunction with intrinsic factor occurs in the cholesterol esterase. terminal ileum; resection of the ileum will result in deficiency of B12 and cause a macrocytic anaemia and Regulation of Exocrine Secretions degeneration of the spinal cord if not corrected. As with gastric secretion, regulation of pancreatic juice Water reabsorption: the ileum plays an important role secretion is divided into three phases: in the absorption of water from bowel contents (espe- cephalic: vagal cially in the elderly); this leads to diarrhoea and an gastric: vagal increase in stool frequency. intestinal: CCK and secretin. 224 SECTION II Physiology Cephalic bile acids: cholic acid and chendeoxycholic acid During the cephalic phase the sight, smell and taste of bile salts: formed by linking the amino acids glycine food cause vagal (parasympathetic) stimulation and the and taurine to bile acids. Bile salts have a hydrophobic release of acetylcholine (ACh) and VIP. These activate and hydrophilic region (amphipathic); this enables the acinar and ductal cells as well as increasing blood them to form an emulsion of lipids in the intestinal flow via vasodilatation. A small stimulus also comes fluid. The emulsion produces a large surface area for from gastrin released from the gastric antrum cells. pancreatic enzymes to act upon; in addition bile salts Gastric form smaller collections of FFAs and monoglycerides Accounts for a relatively small stimulus to secretion; (micelles) to facilitate absorption into enterocytes. gastrin secretion and distension (vagal gastropancreatic The bile salts are not absorbed during this process, reflex) stimulate pancreatic secretion. and remain in the bowel lumen until the distal ileum, Intestinal where they are absorbed (see below) Accounts for 60–70% of the stimulus for pancreatic bile pigments: these are produced by the breakdown secretions; two main hormones are responsible for stim- of the haem unit of haemoglobin; it gives bile its ulating pancreatic secretions: green/yellow colour. The destruction of ageing red cholecystokinin (CCK): release of a fluid rich in blood cells (RBCs) takes place in the spleen; in this enzymes from acinar cells process bilirubin is released into the circulation; it is secretin: release of a bicarbonate-rich fluid. poorly soluble and is transported to the liver bound Factors that promote secretion of these hormones (from to albumin. The bilirubin is conjugated to glucuronic the duodenal mucosa) include: acid in the hepatocytes, producing a water-soluble lipids (CCK) compound that is excreted in bile. In the intestine peptides and amino acids (CCK) bacteria convert these pigments to: acid (secretin). urobilinogen: some is reabsorbed in the intestine and secreted back into the bile or excreted in the Endocrine Secretions urine See Chapter 12. stercobilin and urobilin: give faeces brown colour cholesterol lecithin Clinical Physiology mucus. Physiological Effects of Pancreatic Resection There are two factors that govern bile secretion; one is Removal of the pancreas (pancreatectomy) leads to a range dependent on bile acid recirculation (enterohepatic cir- of physiological abnormalities, including: culation), and the other is independent of this: Malnutrition: inadequate digestion of protein and lip- enterohepatic circulation: >90% of secreted bile acids ids due to the loss of proteolytic and lipolytic enzymes. are reabsorbed from the intestine (distal ileum) and The inadequate breakdown of protein leads to progres- returned to the liver via the portal vein; the remain- sive weight loss and inadequate fat digestion; this leads ing 5–10% of bile acids are altered by bacterial flora to fatty stools and flatus (due to bacterial overgrowth). and become insoluble, and are thus excreted. The The absorption of fat-soluble vitamins (A, D, E and K) rate at which bile acids are returned to the liver will is reduced, and leads to progressive deficiencies. influence the rate at which they are secreted into the Malabsorption: loss of alkaline pancreatic secretions canaliculi leads to failure to neutralize gastric chyme and leads to the remaining components of bile (water, Na+, Fe2+, Ca2+ and PO4− malabsorption; this eventually leads HCO3−) are secreted into the canaliculi indepen- to anaemia and osteoporosis. dently of bile acid recirculation. HCO3− and Na+ are Diabetes mellitus: loss of the pancreas leads to an abso- both actively pumped into the lumen; water follows lute deficiency of insulin. due to the resulting osmotic gradient. Secretion of the bicarbonate-rich fluid is stimulated by secretin, gastrin and glucagon. LIVER AND GALL BLADDER Regulation of secretion: CCK stimulates the contrac- tion of the gall bladder and the release of bile into the Liver duodenum. Bile Production (Fig. 10.6) Hepatocytes secrete fluid into the canaliculi; this fluid is Metabolic Functions very similar to plasma with reference to its ion composi- The liver is responsible for the handling of dietary carbohy- tion; however, it also contains: drate, protein and lipids. WWW.BOOKBAZ.IR  CHAPTER 10 Gastrointestinal System 225 Haemoglobin Globin Haem Fe2+ Porphyrin Bilirubin Plasma Liver albumin Liver Kidney Bilirubin Secreted glucuronide in bile Small n ge intestine o ilin Reabsorbed ob Urobilinogen Small Ur Bile salts intestine Stercobilinogen (= urobilinogen) Absorbed A B Fig. 10.6 (A) Summary of bile pigment metabolism. (B) Enterohepatic circulation of bile salts. Carbohydrate metabolism starvation these stores are released, providing fatty Following a meal the digested components are delivered acids (provides energy as ATP for gluconeogenesis) to the liver via the portal vein; the absorbed glucose is and glycerol (acts as a non-carbohydrate substrate then converted to glycogen (the principal form of stored for gluconeogenesis) carbohydrate; glycogenesis). At times of low blood glu- synthesizes lipoproteins and cholesterol. cose or high energy demand the glycogen within the liver is converted back to glucose (glycogenolysis). Protein Synthesis Protein metabolism As mentioned above, the liver synthesizes all the plasma The liver has a number of roles related to protein proteins (other than immunoglobulins), all the non- metabolism: essential amino acids and many of the clotting factors. able to produce glucose from amino acids and other non-carbohydrate substances (gluconeogenesis); Vitamin D Activation this becomes particularly important in times of pro- Activation of vitamin D is a two-stage hydroxylation longed exercise and depletion of glycogen stores dur- process. The liver performs the first hydroxylation to ing starvation give 25-hydroxycholecalciferol, and the kidney per- involved with synthesis of many of the plasma pro- forms the second to give 1,25-hydroxycholecalciferol. teins, such as albumin and clotting factors also handles the degradation products of amino Detoxification acid metabolism. Use of amino acids throughout the The liver detoxifies a number of substances: body results in the production of ammonia, which is peptide hormones: insulin, Anti-Diuretic Hormone converted to urea. (ADH), growth hormone Lipid metabolism steroid hormones: testosterone, oestrogen, adrenal The liver is involved with several facets of lipid metabolism: cortex hormones glucose is converted to FFAs; this is then trans- catecholamines ported to adipose tissue. It is then combined drugs with glycerol and stored as triglycerides. During toxins. 226 SECTION II Physiology The detoxification process involves two stages: is excreted in the faeces is further altered by bacterial stage 1: increase in the water solubility of the sub- flora and is referred to as stercobilinogen. strate (i.e. the cytochrome p450 system) Prehepatic jaundice stage 2: reduction in biological activity and toxic This is caused by disorders that result in excessive activity. destruction of RBCs (haemolysis); the liver is over- whelmed by the bilirubin that is being produced and Vitamin and Mineral Storage is unable to conjugate it. The jaundice is thus referred The liver stores a number of substances; in addition to to as being an unconjugated hyperbilirubinaemia. This glycogen and fats, it also stores: finding is highly suggestive of a prehepatic cause for the iron jaundice. Other laboratory findings associated with pre- copper hepatic jaundice include: vitamin A, D, E, K and B12. no bilirubin in the urine (unconjugated bilirubin is not water-soluble) Phagocytosis ↑urobilinogen in the urine (as a result of more biliru- Kupffer cells in the hepatic sinusoids remove bacteria, bin being broken down in the intestine) debris and old RBCs. reticulocytosis: in response to the need to replace destroyed blood cells Haemopoiesis anaemia In the embryo the liver is involved in haemopoiesis; ↑lactate dehydrogenase (LDH) in adults it only plays a role in disease states such as ↓haptoglobin: protein that binds free haemoglobin chronic haemolysis (extramedullary haemopoiesis). and transfers it to the liver. Common causes of prehepatic jaundice include: inherited: Clinical Physiology red cell membrane defects, e.g. hereditary sphero­- Jaundice cytosis Defined as the yellow pigmentation of the skin and eyes haemoglobin abnormalities, e.g. sickle cell disease as a result of excess bilirubin in the circulation; this metabolic defects, e.g. G6PD deficiency usually becomes clinically detectable at plasma levels acquired: >40 µmol/L (normal range is