1. Physiology of Digestion Department of Physiology School of Medicine University of Sumatera Utara Dr. Yudi Herlambang Prof dr Abdul Majid Dr Nuraiza Nuraiza Meutia

2. Food Nutrient Non Nutrient Assimilated Eliminated Digestive system Primary Functions of Digestive System Activity necessary: MotilitySecretionDigestionAbsorption

3. Movement of food through tract,includes ingestion, mastication (chewing food and mixing with saliva), deglutition (swallowing) and peristalsis (rhythmic contractions along GI tract that propel food) muscular contraction.  muscular contraction. Primary Functions of Digestive System Activity necessary:Motility Secretion Endocrine (secretion of hormones that regulate digestive process) enzyme & other digestive juices.Exocrine (secretion of water, enzymes, acid, bicarbonate, into GI tract  enzyme & other digestive juices.

4. Hydrolysis reactions that break ingested polymers (large molecules) into their smaller subunits (monomers)  breakdown of substances. –proteins into amino acids –fats into glycerol and free fatty acids –complex sugars into monosaccharides Digestion Transfer of monomer subunits across wall of small intestine into blood or lymph transport modified nutrients.  transport modified nutrients. Absorption

6. Histology of the Alimentary Canal Figure 23.6

7. Regulation; There are two ‘nerve nets’ (plexuses) in GI tract that contain neurons and interneurons –sub mucosal (Meissner) –Myenteric (Auerbach) Plexuses = brain of the gut –stimulated by stretch (bolus of food), chemicals, and stomach content (local stimuli) Activity of plexuses can be modified by central nervous system and the autonomic nervous system Neural:

8. Neural regulation via autonomic nervous system Neural regulation via autonomic nervous system – GI tract receives both sympathetic and parasympathetic innervations Parasympathetic via vagus nerve and spinal nerves in sacral region (to lower portion of large intestine) Parasympathetic via vagus nerve and spinal nerves in sacral region (to lower portion of large intestine) → stimulates motility and secretion; favors digestion Sympathetic Sympathetic → reduces motility and secretory activity and stimulates sphincter contraction

9. Paracrine regulation Paracrine regulation – production of hormone-like molecules that are produced in one cell and travel through interstitial fluid (not bloodstream) to affect activity of nearby cells Hormone regulation Hormone regulation – production of hormones that are released into the bloodstream and carried to target tissues within digestive system where they affect digestive activity Hormonal.

10. Nervous Control of the GI Tract Figure 23.4

11. Components of Digestive System Organs of GI tract include : Organs of GI tract include : – oral (buccal) cavity (mouth) and pharynx – esophagus – stomach – small and large intestine – rectum and anus. Accessory digestive organs include : Accessory digestive organs include : – teeth, tongue, and salivary glands – liver and gall bladder – pancreas

12. 4 layers of the GIT wall Epithelial lining cellsEpithelial lining cells Lamina propria:Lamina propria:  loose connective tissue.  blood & lymph vessel.  immune system cells (macrophage, lymphoid tissue, lymphocytes, IgA, IgM) 1. Tunica Mucosa:

13. Muscularis mucosaeMuscularis mucosae  inner circular fibers.  outer longitudinal fibers. Villi.Villi. Microvilli.Microvilli.

14. 2. Tunica Submucosa: Blood & lymphatic vesselsBlood & lymphatic vessels Nerve plexus (enteric nervous system)Nerve plexus (enteric nervous system)  submucosal nerve plexus (Meissner)  submucosal nerve plexus (Meissner) control secretion in the GIT control motility o/t villi

15. 3. Tunica Muscularis: Innermost circular layer   Ø intestinal lumen.Innermost circular layer   Ø intestinal lumen. Myenteric nerve plexus (Auerbach)Myenteric nerve plexus (Auerbach) control of motility. Outer longitudinal layer  shorten the tubeOuter longitudinal layer  shorten the tube 4. Tunica serosa (adventitia): Outermost layer.Outermost layer. Larger nerves & blood vessels travel in a bed of connective & adipose tissue.Larger nerves & blood vessels travel in a bed of connective & adipose tissue.

16. Mouth:

17. Salivary Glands Terdiri dari 3 pasang extrinsic glands : parotid, submandibular, dan sublingual Ditambah Intrinsic salivary glands (buccal glands) : tersebar di mucosa oral.

18. Teeth – grind and tear food into smaller pieces – increases surface area upon which digestive enzymes work parotid gland parotid duct sublingual gland submandibular gland Mouth: Salivary glands (parotid, submaxillary, sublingual) secrete saliva lubricates and softens food; aids in swallowing contains amylase = enzyme that begins breakdown of carbohydrates

19. SALIVARY GLANDS Sympathetic and parasympathetic responses are not antagonistic 1. Parasympathetic system has the dominant role - continuous 2. Increased parasympathetic stimulation produces a watery saliva rich in enzymes 3. Increased sympathetic stimulation produces a smaller volume of thick saliva rich in mucus  inhibits secretion (dry mouth when nervous) NB Salivary secretion is the only digestive secretion completely under neural control

20. CONTROL OF SALIVARY SECRETION cerebral cortex salivary centre in medulla autonomic nerves salivary glands  salivary secretion pressure receptors and chemoreceptors in the mouth other inputs Conditioned reflex simple reflex

21. Oropharynx To convey food into the esophagus. Important role in swallowing.

22. Cavity at back of mouth opening to both esophagus (digestive tract) and trachea (windpipe) Voluntary raising of larynx to close (epi)glottis and prevent food entry into windpipe Pharynx = throat

23. Esophagus. Hollow muscular tube connecting pharynx and stomach. Bounded by sphincters. Lined w/ stratified squamous epithelium. Disorder o/t LES tone  major cause esophageal reflux  heart burn.(GERD)

28. Stomach wall

30. Stomach : –Temporary stores ingested food.  sphincters prevent backward flow of materials into esophagus and regulate release of stomach contents into small intestine –Churn, mixes food with gastric juice. –Mechanical and chemical breakdown of ingested material –Produces, mucus, HCl and pepsinogen. –HCl converts pepsinogen into pepsin. –Sterilization of stomach contents by acid –Pepsin digests proteins into peptide fragments. –Absorbs some water, alkohol, glucose. –Binds vit. B 12  allows abs. in ileum Secretion/Digestion

31. Pada Epitel terdapat Goblet cells yang manghasilkan lapisan mukus alkalin. Pada Gastric pits terdapat gastric glands yang mensekresi gastric juice, mukus, dan gastrin

32. Variety of secretory cells : – Mucous neck cells : acid mucus – Parietal cells : HCl dan intrinsic factor – Chief cells : pepsinogen – Enteroendocrine cells : gastrin, histamine, endorphins, serotonin, cholecystokinin (CCK), dan somatostatin ke lamina propria Pepsinogen HCl Gastrin Histamine

33. Regulation of Gastric Secretion Pengeluaran cairan lambung diatur oleh mekanisme neural dan hormonal. Proses stimulasi atau inhibisi berlangsung dalam 3 fase : – Cephalic (reflex) phase: sebelum makanan masuk – Gastric phase: ketika makanan masuk ke lambung – Intestinal phase: ketika sebagian dari makanan yang sudah dicerna masuk ke duodenum

34. 1.Cephalic Phase Hal yang dapat merangsang : – Melihat atau memikirkan makanan – Stimulasi reseptor pengecap atau penghidu Hal yang dapat menghambat : – Depresi atau hilang nafsu makan – Penurunan stimulasi parasimpatetik

35. Figure 24.15a

36. 2.Gastric Phase Hal yang dapat merangsang : – Stomach distension – Activation of stretch receptors (neural activation) – Activation of chemoreceptors by peptides, caffeine, and rising pH – Release of gastrin to the blood Hal yang dapat menghambat : – A pH lower than 2 – Emotional upset that overrides the parasympathetic division

37. Figure 24.15b

38. 3. Intestinal Phase Excitatory phase : low pH(keasaman meningkat); makanan yg sebagian telah dicerna memasuki duodenum dan mendorong /mengaktifkan kelenjar di lambung. Inhibitory phase : distensi duodenum, adanya lipid, acidic, atau kimus hipertonik, dan bahan iritan di duodenum (Initiates inhibition of local reflexes and vagal nuclei) (Closes the pyloric sphincter) (Releases enterogastrones that inhibit gastric secretion

39. Figure 24.15c

40. Gerakan Lambung

41. Gastric Contractile Activity Peristaltic waves move toward the pylorus at the rate of 3 per minute This basic electrical rhythm (BER) is initiated by pacemaker cells (cells of Cajal) Most vigorous peristalsis and mixing occurs near the pylorus Chyme is either: – Delivered in small amounts to the duodenum or – Forced backward into the stomach for further mixing

42. Gastric Contractile Activity Figure 23.18

43. Regulation of Gastric Emptying Gastric emptying is regulated by: – The neural enterogastric reflex – Hormonal (enterogastrone) mechanisms These mechanisms inhibit gastric secretion and duodenal filling Carbohydrate-rich chyme quickly moves through the duodenum Fat-laden chyme is digested more slowly causing food to remain in the stomach longer

44. Regulation and Mechanism of HCl Secretion Sekresi HCl distimulasi oleh ACh, histamine, dan gastrin melalui sistem second- messenger Release of hydrochloric acid: – Is low if only one ligand binds to parietal cells – Is high if all three ligands bind to parietal cells Antihistamines block H 2 receptors and decrease HCl release

45. Regulation and Mechanism of HCl Secretion Figure 23.17

47. Hormones Released During the Intestinal Phase When acidic chyme arrives, hormones are released by the duodenum. 1. Secretin stimulates pancreas to secrete bicarbonate ions that neutralise stomach acid inhibits gastric secretion and motility of stomach 2. Cholecystokinin (CCK) stimulates production / release of pancreatic enzymes stimulates bile release from gallbladder inhibits gastric secretion and motility of stomach

48. Digestion in the stomach CHO digestion is halted because acidic pH of the stomach inactivates salivary amylase CHO digestion is halted because acidic pH of the stomach inactivates salivary amylase Little fat digestion occurs in the stomach Little fat digestion occurs in the stomach Protein digestion begins in the stomach Protein digestion begins in the stomach – Involves mechanical breakdown of proteins by the churning actions of the stomach – Involves the chemical digestion of proteins by acid and hormones Gastric (stomach) acid = hydrochloric acid (HCl) Gastric (stomach) acid = hydrochloric acid (HCl) Pepsin Pepsin

49. Protein Digestion in the Stomach Parietal cells Parietal cells – secrete acid (hydrochloric acid = HCL) & intrinsic factor – stimulated to produce acid by gastrin Chief cells Chief cells – secrete pepsinogen & gastric lipase Pepsinogen = inactive hormone Pepsinogen = inactive hormone Pepsinogen converted to pepsin (active hormone) by acidic pH of the stomach Pepsinogen converted to pepsin (active hormone) by acidic pH of the stomach Pepsin breaks large proteins down into smaller peptides Pepsin breaks large proteins down into smaller peptides

50. G cells G cells – Secrete gastrin – Gastrin = hormone target tissues = chief cells and parietal cells in stomach target tissues = chief cells and parietal cells in stomach stimulates gastric juice production stimulates gastric juice production – HCL from parietal cells – Pepsinogen from chief cells Decreases pH of stomach Decreases pH of stomach – Promotes conversion of pepsinogen to pepsin Protein Digestion in the Stomach

51. – It also activates gastroileal reflex which moves chyme from ileum to colon – Parasympathetic stimulation releases gastrin releasing peptide (GRP), which stimulates G cell release of gastrin – Mucus cells - secretes mucus to protect epithel against acid and digestive enzymes

52. Absorption in the Stomach Almost all products of digestion are absorbed in the intestine Notable exceptions –alcohol and aspirin can be absorbed directly through stomach wall –due to their lipid solubility –absorption of aspirin through stomach wall associated with bleeding, may be related to peptic ulcers in people taking large dosages

53. Chyme Food in stomach is liquified –mixed with stomach juices to form pasty liquid material = chyme Chyme = material passed from stomach to small intestine

54. Small Intestine Functions in digestion –CHO digestion resumes and is completed here –Protein digestion continues and completes here –Fat digestion is initiated and completed here Also functions to absorb nutrients, fluids, and electrolytes Divisions (@ 12 feet long total length) 3 segments (12 ft long, 22 ft in cadaver) duodenum = upper portion (@ 1 foot long) closest to stomach jejunum = middle section ileum = lower section closest to large intestine

55. Features that increase surface area – Circular folds Project into lumen 3-10 mm Prominent in duodenum and jejunum and disappear near mid ileum – Villi 4-5 million in entire length 0.5-1.5 mm long

56. Anatomy – Microvilli 1.0 um long Brush border

57. Physiology Two primary function – Digestion – Absorption of nutrients and water Digestion – Mainly in duodenum – small intestine and pancreatic enzymes – Bicarbonate from pancreas neutralizes acids – Mucous protects from acids – Bile emulsifies fats

58. Hormones Important in Sm. Intestine Digestive Activity Secretin Cholecyctokinin (CCK) Enterokinase Pancreatic enzymes –Lipase, Amylase, Peptidases, Trypsinogen, Trypsin

59. Physiology – Digestive enzymes Salivary amylase Pepsin Pancreatic enzymes: – Trypsin – Chymotrypsin – Carboxypeptidase – Nucleases – Pancreatic lipase – Pancreatic amylase Intestinal enzymes: – Peptidases – Disaccharidases – Lipase – Nucleotidases

60. Physiology – Hormones Cholecystokinin – secretion stimulated by fat in duodenum – Contraction of gall bladder – Pancreatic secretion of enzyme rich material Secretin – secretion stimulated by low pH in duodenum – Secretion of bile from the liver – Pancreatic secretion of HCO 3 - rich juice

61. Physiology Absorption – Nutrients broken down into simple sugars, fatty acids and amino acids – Principle sites of absorption Duodenum: iron, calcium, vitamins, fats, sugars, amino acids, vitamins Jejunum: fat, sugar, amino acid (largely complete by mid jejunum), vitamins Ileum: vitamin B 12 and bile salts – Most bile salts are absorbed and recirculated to the liver – important in maintaining bile pool

62. Brush border enzymes reassembly

64. Intestinal Contractions and Motility 2 major types of contractions occur in the small intestine: – Peristalsis: Slow movement. Pressure at the pyloric end of small intestine is greater than at the distal end. – Segmentation: Major contractile activity of the small intestine. Contraction of circular smooth muscle. – Mix chyme. Insert fig. 18.14

65. Contractions of Intestinal Smooth Muscles Occur automatically in response to endogenous pacemaker activity. Rhythm of contractions is paced by graded depolarizations called slow waves. – Slow waves produced by interstitial cells of Cajal. – Slow waves spread from 1 smooth muscle cell to another through nexuses.

67. When slow waves above threshold, it triggers APs by opening of VG Ca 2+ channels. Inward flow of Ca 2+ : – Produces the upward depolarization phase. – Stimulates contraction of smooth muscle. Repolarization: – VG K + channels open. Slow waves decrease in amplitude as they are conducted. May stimulate contraction in proportion to the magnitude of depolarization. Parasympathetic NS, stretch and gastrin increase the amplitude of slow waves. – Stimulate APs. SNS decrease APs. Contractions of Intestinal Smooth Muscles

68. Cells and Electrical Events in the Muscularis

69. Digestion Most occurs by hydrolysis reactions - reactions that add water to break chemical bonds Enzymes involved: –amylase - breaks complex sugars to disaccharides –lipases - breaks down lipids –proteases - breaks down proteins

70. Hormonal Control of Intestinal Secretion S cells secrete secretin –secretin target tissue = pancreatic ducts and liver –induces release of water and HCO 3 - from pancreatic duct cells and secretion of HCO 3 - into bile by liver –HCO 3 - neutralizes acidic chyme Stimuli for secretin secretion –acid (pH less than 4.5 stimulates secretion) –secretin = nature’s antacid

71. I cells secrete cholecystokinin (CCK) –CCK target tissues = pancreatic acinar cells and gall bladder –induces secretion of digestive enzymes from pancreatic acinar cells –induces contraction of gall bladder, which releases bile into small intestine Stimuli for CCK secretion –presence of protein and/or fat in chyme Hormonal Control of Intestinal Secretion (continued)

72. CCK and Appetite Control CCK also thought to act on satiety center in brain and inhibit appetite Butabindid = drug that interfers with enzyme responsible for CCK degradation (breakdown) –keeps CCK in system longer –boosts appetite inhibition –used to treat obesity

73. Pancreatic Enzymes Amylase - breaks CHO starch to maltose, maltriose, and small branched structures Lipase - breaks down triglycerides into fatty acids and glycerol Proteolytic enzymes break peptides down to amino acids and dipeptide fragments Trypsinogen –converted to trypsin by enzyme (enterokinase) located along inner wall of small intestine –trypsin converts other pancreatic zymogens (inactive forms) to their active forms within the small intestine

74. Pancreatic Enzymes (continued) Most pancreatic enzymes are produced as inactive molecules = zymogens Are transported to small intestine in zymogen form Protects the pancreas from ‘self digestion’

75. CHO Digestion in Sm. Intestine Pancreatic amylase secreted into duodenum in response to secretin  Is active in the intestine because the acidic chyme is neutralized by HCO 3 - also secreted from pancreas in response to secretin Amylase converts complex CHOs to maltriose, maltose, and short branched sugars

76. Small Intestine (continued) Inner surface (epithelial layer) extensively folded and covered with smaller folds (villi) and even smaller folds (microvilli) increase surface area for absorption to occur Site of absorption of carbohydrates, lipids, amino acids, calcium and iron in duodenum and jejunum Bile salts, Vit B 12, water, and electrolytes mainly in ileum

77. CHO Absorption in the Sm. Intestine Enzymes in the brush border complete breakdown of maltotriose, maltose, and branched sugars, lactose and sucrose Lactase converts lactose to glucose and galactose Sucrase converts sucrose to glucose and fructose Isomaltase converts branched sugars glucose, maltose and unbranched short oligosaccharides Maltase converts maltose to glucose

78. Epithelial cells that line the sm. Intestine absorb monosaccharides by active or facilitated transport Glucose and galactose are actively co-transported with sodium using the same transporter and Fructose is absorbed by passive facilitated transport using a different transporter protein than that used by glucose and galactose Monosaccharides enter bloodstream and are transported to liver and converted to glycogen or sent to bloodstream for immediate, direct ultilization or storage by cells CHO Absorption in the Sm. Intestine (continued)

79. Fat Digestion in Sm. Intestine Limited fat digestion occurs prior to sm. Intestine –Some lipases in saliva and gastric secretions Lipase = enzyme important in fat digestion –Secreted into sm. intestine from pancreas in response to secretin –breaks down triglycerides to free fatty acids and monoglycerides –Activity is dependent upon the amount of surface area on which it can work Phospholipase A 2 digests phospholipids Bile is essential for proper fat digestion

80. Digestion and Absorption of Lipids in Small Intestine Fats stimulate I cell release of CCK CCK triggers release of bile from gall bladder Bile emulsifies fats –breaks large fat globules into smaller globules  does not actually break bonds between glycerol and fatty acids –Increases surface area available for pancreatic lipase to act

81. Liver Largest organ in body Blood supply –hepatic artery delivers oxygenated blood –hepatic portal vein products absorbed into capillaries in the intestines do not directly enter general circulation this blood is delivered first to the liver by the hepatic portal vein, and then passed on to the general circulation liver has ‘first crack’ at absorbed nutrients, except lipids

82. Liver (continued) Digestive functions –secretes bile - essential for digestion and absorption of fats – Function - overall is to filter and process nutrient-rich blood, not just a digestive function regulates carbohydrate metabolism through glycogen storage and release regulates many aspects of lipid metabolism, eg., cholesterol synthesis and release of ketones detoxifies blood urea and bile synthesis

83. PANKREAS

84. Figure 24.21a, b Gallbladder

86. Divisions –cecum = section nearest small intestine (appendix attached in this region) –colon = major portion ascending transverse descending sigmoid (leads to rectum) Large Intestine

87. Functions (converts chyme to feces) – Absorption of water and electrolytes (mainly on right side) Absorbs 800 ml water/day Capacity 1500-2000 ml/day (when exceeded results in diarrhea) – Sigmoid colon reservoir for dehydrated fecal mass ~200 g feces/day – Water – 80-90% – Food residue – Bacteria – Cells – Unabsorbed minerals

88. – Secretes mucus (no enzymes) – Bacteria produce vitamin K and several B’s – Flatus (NH 3, CO 2, H 2, H 2 S, CH 4 ) CO 2 produced when fatty acids and HCl are neutralized by bicarbonate Bacterial fermentation of carbohydrates produces CO 2, H 2, CH 4 ~1000 ml expelled each day Excess occurs with aerophagia and diets high in indigestible carbohydrates – Rectum and anus sites of some of most common disorders known to humans Constipation Hemorrhoids Abscesses and fistulas Colon and rectal cancer

89. Bacteria live in the colon and stimulate the production of vitamin K and some of the B complex vitamins Mucus is produced but no enzymes are secreted in the large intestine Mass Peristaltic Movements (2-3x day) Moves through in 12-24 hours

90. DIGESTIVE ACTIVITIES OF LARGE INTESTINE STRUCTUREACTIVITYRESULT MucosaSecretes mucus Lubricates colon & protects mucosa Absorbs waterMaintains water balance; solidifies feces; absorbs vitamins & some ions

91. DIGESTIVE ACTIVITIES OF LARGE INTESTINE STRUCTUREACTIVITYRESULT LumenBacterial activity Breaks down undigested carbohydrates, protein, & amino acids into products that can be expelled in feces or absorbed & detoxified by liver Synthesizes certain B vitamins & vitamin K

92. DIGESTIVE ACTIVITIES OF LARGE INTESTINE STRUCTUREACTIVITYRESULT MuscularisHaustral churning Contractions move contents from haustrum to haustrum PeristalsisContractions of circular & longitudinal muscles move contents along length of colon

93. DIGESTIVE ACTIVITIES OF LARGE INTESTINE STRUCTUREACTIVITYRESULT MuscularisMass peristalsis Forces contents into sigmoid colon Defecation reflex Eliminates feces by contractions in sigmoid colon & rectum

94. Secretion & H 2 O absorption 2000 ml – 150 ml = ?

95. Ion & Vitamin absorption

96. Rectum

97. The Defecation Reflex

98. Defecation process Reflex relaxation of internal sphincter Valsalva maneouvre raising intraabdominal pressure Relaxation of puborectalis (anorectal angle) Voluntary relaxation of external sphincter

99. Defecation reflex > 15 mm Hg

100. Continence mechanism Rectum normally empty Colonic movements distend rectum - 150 mls, 25 cm H2O which activate defecation reflex Voluntary inhibition (external sphincter) – movement of faecal material back into colon

101. Disorders of the GI tract Mouth and throat – gingivitis - infection of the gum, can lead to periodonititis involving the supporting bone of the teeth – Vincent’s disease - a kind of gingivitis caused by a spirochete – Leukoplakia - characterized by thickened white patches on the mucous membranes of the mouth - common in smokers and may be a precursor to cancer

102. Symptoms of esophageal disorders Dysphagia – Subjective awareness of an impairment of swallowing – Major symptom for diseases of the pharynx or esophagus – Occurs in some non-esophageal disorders resulting from vascular or neurologic disease – May be of obstructive or motor origin Obstructive causes – Stricture – Tumors Motor causes – Impaired peristalsis – Dysfunction of UES or LES – Common motor disorders – achalasia, scleroderma, diffuse esophageal spasm

103. Symptoms of esophageal disorders – cont. Pyrosis (heart burn) – Caused by reflux of gastric acid or bile secretions – Persistent reflux caused by incompetent LES – results from excess stretching of the lower esophagus; not due to hyperacidity of the stomach Odynophagia – Pain induced by swallowing Regurgitation – Back flow into mouth – Effortless (as opposed to vomiting) – Common in infants – Reflects both LES incompetence and failure of UES to serve as regurgitation barrier

104. Disorders of esophageal motility Achalasia – Definition = uncommon hypomotility disorder characterized by weak and uncoordinated peristalsis or aperistalsis within the body of the esophagus, elevated LES pressure and failure of LES to relax completely Foods and liquids accumulate in lower esophagus – Exact etiology unknown May be degeneration of Aurbach’s plexus – Most common symptom is dysphagia Regurgitation during meals Nocturnal regurgitation may result in aspirations and chronic pulmonary infections or sudden death Food in esophagus may lead to inflammatory changes, erosions, or cancer

105. Disorders of esophageal motility Achalasia - cont. – Treatment Palliative, measures to relieve obstruction of lower esophagus – No way to restore peristalsis Two forms of therapy – Dilation of LES with pneumatic bag or mercury filled bag (bougie) – Surgery to open LES accompanied by pyloroplasty

106. Disorders of esophageal motility – cont. Diffuse esophageal spasm – Definition = uncoordinated, nonpropulsive contractions in response to swallowing – Cause unknown – more common in patients > 50 Fairly common – Usually asymptomatic Sometimes dysphagia and odynophagia that are aggravated by cold foods, large boluses and nervous tension Sometimes chest pain that may be confused with angina – Treatment Avoid cold foods and large meals Antacids, sedatives, nitroglycerine Esophageal dilation is symptoms persistent and distressing

107. Disorders of esophageal motility – cont. Scleroderma – Esophageal motor dysfunction occurs in > 2/3 of patients with progressive systemic sclerosis (scleroderma) – Atrophy of smooth muscle in lower portion of esophagus – Incompetence of LES often leads to reflux esophagitis and subsequent stricture formation in lower esophagus

108. Esophagitis Definition = inflammation of the esophageal mucosa May be acute or chronic – Innocuous type follows ingestion of hot liquids – Most common significant form caused by acid reflux – Are infectious forms – Candida albicans (thrush), herpes virus – Acute, severe follows ingestion of strong alkalis or acids

109. This is Candida esophagitis. Tan-yellow plaques are seen in the lower esophagus, along with mucosal hyperemia. The same lesions are also seen at the upper right in the stomach

110. The lower esophagus here shows sharply demarcated ulcerations that have a brown-red base, contrasted with the normal pale white esophageal mucosa at the far left. Such "punched out" ulcers are suggestive of herpes simplex infection.

111. Esophagitis Chronic reflux esophagitis and Hiatus Hernia – Most common form – Cause – incompetence of LES and reflux of gastric or intestinal juice into esophagus often associated with hiatus hernia – Mechanisms that prevent reflux Tone of sphincter in LES Angle of entry – creates a flap valve Intra-abdominal pressure closes segment of esophagus below diaphragm

112. Esophagitis – cont. – Hiatus (hiatal) hernia Herniation of portion of stomach into chest 2 types – Direct or sliding (most common) » Gastroesophageal junctions slides into thoracic cavity » LES opens causing reflux » Often asymptomatic – Paraesophageal or rolling » Part of fundus roles through hiatus » LES remains competent and no reflux » Major complication is strangulation Important clinical consideration is if there is reflux

113. Esophagitis – cont. Treatment of sliding hernia – Goal is to prevent reflux or neutralize reflux » Frequent small meals » H 2 blockers (ranitidine) » Protective agents (sucraflate) » Loose weight » Avoid stooping forward » Elevate head during sleep – Surgery if evidence that persistent reflux is causing esophagitis or stricture formation

114. Disorders of the GI tract Stomach – Hiatal hernia - a weakness in the diaphragm at the point where the esophagus connects allowing the stomach or other abdominal organs protrude upwards – nausea and vomiting - caused by an interruption of forward movement of nutrition; reverse peristalsis

115. Disorders of the GI tract Stomach, continued – gastritis - inflammation of the stomach mucosa; causes include irritation by spicy food, drugs, alcohol, or nicotine – stomach cancer - males are more susceptible than females; symptoms usually long standing indigestion – peptic ulcer - most common ages 30-45; causative factors include smoking, drinking; anti-inflammatory drugs and bacterium, Helicobacter pylori

116. Gastritis – inflammation or hemorrhagic condition of the mucosa Acute superficial gastritis – Erodes surface of epithelium in diffuse or localized patterns – Causes Drugs – NSAIDS Chemicals – alcohol, bile acids, pancreatic enzymes, caffeine, strong spices Helicobacter pylori – Clinical manifestations Vague abdominal discomfort Epigastric tenderness Bleeding Vomiting Hematemesis

117. This is a typical acute gastritis with a diffusely hyperemic gastric mucosa. There are many causes for acute gastritis: alcoholism, drugs, infections, etc.

118. Gastritis – inflammation or hemorrhagic condition of the mucosa - cont. – Usually resolves when offending agent removed Antiemitic drugs to relieve nausea and vomiting May need to correct fluids and electolytes Acid blockers and antacids Sulcrafate to coat stomach lining

119. Gastritis - cont. Chronic atrophic gastritis – Progressive atrophy of glandular epithelium with loss of parietal and chief cells Decreased HCl, pepsin and intrisic factor production – Caused mainly by H. pylori More often in elderly Alcohol, hot tea and smoking may predispose – May lead to gastric ulcers or carcinoma

120. Gastritis is often accompanied by infection with Helicobacter pylori. This small curved to spiral rod-shaped bacterium is found in the surface epithelial mucus of most patients with active gastritis. The rods are seen here with a methylene blue stain.

121. This of gastric mucosa reveals the presence of many short, curved rod-like organisms overlying the mucosa. These are Helicobacter pylori organisms, whose home is the gastric mucus. The incidence of H. pylori infection increases with age, with half of American adults infected by age 50. H. pylori organisms break down mucosal glycoproteins and damage epithelial cells, leading to inflammation--a chronic gastritis that is asymptomatic in most cases. Peptic ulcer disease, particularly duodenal ulceration, is strongly associated with H. pylori infection, which may also play a role in development of gastric carcinoma. Antibiotic treatment of H. pylori reduces these complications

122. Gastritis - cont. – Symptoms generally varied and vague Feeling of fullness Anorexia Vague epigastric distress – Treatment varies depending on cause Antibiotics Avoid irritants Correct iron deficiency if present Vitamin B 12 supplement

123. Peptic ulcer disease General consideration – Definition = circumscribed breaks in the continuity of the mucosa, extending below the epithelium Erosions – do not extend below epithelium Chronic ulcers have scar tissue at base, acute don’t – Can be anywhere in GI tract exposed to acid- pepsin gastric juice Other factors also contribute – H. pylori – Mucosal bicarbonate secretion – Stress – Genetics

124. A 1 cm acute gastric ulcer is shown here in the upper fundus. The ulcer is shallow and sharply demarcated, with surrounding hyperemia. It is probably benign. However, all gastric ulcers should be biopsied to rule out a malignancy.

125. The strongest association with Helicobacter pylori is with duodenal peptic ulceration--over 85% of duodenal ulcers. Seen here is a penetrating acute ulceration in the duodenum just beyond the pylorus. An acute duodenal ulcer is seen in two views on upper endoscopy in the lower panels.

126. Peptic ulcer disease - cont. Pathogenesis – Two factors prevent stomach from digesting itself Gastric mucosal barrier – First line of defense – NSAIDS cause changes in mucosa that my facilitate its digestion by pepsin – Destruction of barrier believed to be important factor in pathogenesis of gastric ulcers » Results of back diffusion of H + injuring underlying tissues » Antrum more susceptible to back diffusion than fundus » Duodenum resistant to ulceration due to Brunner’s glands which produce a highly alkaline secretion

127. Peptic ulcer disease - cont. Epithelial barrier – Depends on abundant vascular supply and continual, rapid regeneration of epithelial cells (~3 days) – Other factors 500,000 new cases/year (10-12 % of population affected) Duodenal ulcers occur in much younger group than gastric Lower incidence in women Caffeine increases acid production Emotional stress (how one deals with stress) >90% of duodenal ulcers are on anterior or posterior wall within 3 cm of pyloric ring 40-60% have family history

128. Peptic ulcer disease - cont. Clinical features – Principle feature is chronic, intermittent epigastric pain – typically relieved by food – ~25% have bleeding (more common with duodenal) – Other signs and symptoms Vomiting Red or “coffee-ground” emesis Nausea Anorexia Weight loss – Pain-food-relief pattern may not be typical of gastric ulcers – food sometimes aggravates

129. Peptic ulcer disease - cont. Benign vs malignant ulcers – 4% of gastric ulcers are malignant – Malignant (carcinoma) ulcers have shaggy, necrotic base while benign have smooth, clean base

130. Peptic ulcer disease - cont. Medical treatment – Primary consideration is to inhibit or buffer acid to relieve symptoms and promote healing Antacids – increase pH so pepsin isn’t activated Dietary management – small frequent meals, avoid alcohol and caffeine Anticholinergics – inhibit vagal stimulation Antimicrobial therapy Physical and emotional rest – Ulcers caused by H. pylori are successfully treated with antimicrobial agents, bismuth salts, and H 2 blockers – 65-95% eradication rates

131. Peptic ulcer disease - cont. Complications – Hemorrhage Most frequent complication – 15-20% Most common in ulcers of the posterior wall of duodenal bulb due to proximity of arteries Symptoms depend on severity – Anemia – Occult blood in stool – Black and tarry stool – Hematemesis – Shock Mortality up to 10% - higher for patients over 50

132. Peptic ulcer disease - cont. – Perforation Approximately 5% of all ulcers perforate - accounts for 65% of deaths from peptic ulcers Usually on anterior wall of duodenum or stomach Thought to be due to excess acid and often a result of NSAIDS Characteristic presentation – Sudden onset of excruciating pain in upper abdomen – chemical peritonitis – Patient fears to move or breath – Abdomen becomes silent to auscultation and board like rigidity to palpation Treatment – immediate surgery

133. Peptic ulcer disease - cont. – Obstruction Obstruction of gastric outlet in ~5% of patients Due to inflammation and edema, pylorospasm or scarring More often with duodenal ulcers Symptoms – Anorexia – Nausea – Bloating after eating – Pain and vomiting when severe Treatment – Restore fluids and electrolytes – Decompress stomach with nasogastric tube – Surgical correction - pyloroplasty

134. Peptic ulcer disease - cont. – Intractability Medical therapy fails to control symptoms adequately, resulting in frequent, rapid recurrences – Typically surgery is recommended

135. Peptic ulcer disease - cont. Surgical treatment – for patients who do not respond to therapy – For duodenal ulcers aim is to permanently reduce stomach’s capacity to secrete acid and pepsin Vagotomy – Cut vagal branches to stomach – Eliminates cephalic phase – Several techniques Antrectomy – Removal of entire antrum – Eliminates gastric phase Vagotomy plus antrectomy – Eliminates both cephalic and gastric phases

136. Peptic ulcer disease - cont. Partial gastrectomy – Removal of distal 50-75% of stomach – Gastric remnant anastamosed to duodenum (Billroth I) or jejunum (Billroth II) – For gastric ulcers Usually partial gastrectomy and a gastroduodenal anastomosis Normally do not do vagotomy as patients have normal to low acid production

137. Peptic ulcer disease - cont. Postoperative Sequelae – Dumping syndrome ~20% of patients Rapid emptying of hyperosmotic chyme into intestine Rapid fluid shift from vascular compartment into intestinal lumen Hypotension Reflex tachycardia, diaphoresis and vasoconstriction Feeling of fullness, nausea, vomiting and diarrhea common Symptoms usually during or within minutes of meal

138. Peptic ulcer disease - cont. – Hypoglycemia May occur within 2-3 hrs after eating Due to excess release of enteroglucagon from intestine which sensitizes beta cells Over corrects the hyperglycemia Treatment – Eat frequent, small meals – Low carbohydrate and high protein diet – Restrict liquids at mealtime

139. Malabsorption – intestinal mucosal absorption of single or multiple nutrients is impaired resulting in inadequate movement of digested food into blood or lymphatic system Causes (box page 346) – Prior gastric surgery – Pancreatic disorders Chronic pancreatitis, cancer, cystic fibrosis – Hepatobiliary disease Bile tract obstruction, cirrhosis, hepatitis – Disease of small intestine Nontropical sprue, enteritis. giardiasis – Hereditary disorders Lactase deficiency – Drug-induced malabsorption Neomycin, calcium carbonate

140. Disorders of the GI tract Stomach, continued – pyloric stenosis - more common in males than females, causes persistent vomiting because of the stricture in the pyloric sphincter; requires surgery to repair

141. Disorders of the GI tract Intestinal disorders – diarrhea - abnormal frequent watery stools; danger is dehydration and electrolyte imbalance; cause is excess activity of the colon, faulty absorption or infection – constipation - acute due to obstruction or diverticular inflammation (diverticulitis). Chronic includes spastic constipation caused by overuse of laxatives or enemas; flaccid constipation usually caused by inactivity

142. Intestinal obstruction Definition = an interference with the normal flow of intestinal contents through the intestinal tract – May be acute or chronic, partial or complete Chronic obstruction usually involves colon as a result of a tumor Most obstructions involve SI Complete is serious and requires early diagnosis and emergency surgery to save life

143. Intestinal obstruction 2 types of obstructions – Non-mechanical – peristalsis is inhibited by toxic or traumatic alteration in motility – Mechanical – caused by extrinsic pressure Simple mechanical obstruction – only one point of obstruction Closed-loop obstruction – at least 2 points of obstruction (can lead to infarction due to strangulation)

144. Intestinal obstruction Etiology – Non-mechanical Common after abdominal surgery Can be caused by peritonitis Accompanies many traumatic conditions (rib fracture, concussion of spinal cord or fracture of spine) – Mechanical About 50% of all are in adults and result from adhesions following previous surgeries Malignant tumors, diverticulitis and vulvulus are the most common causes in middle aged and older people Inguinal or femoral hernia common causes of SI obstruction Intussusception is the most common cause in infants and small children Foreign objects and congenital abnormalities also common causes in infants and children

145. Intestinal obstruction Pathophysiology – events similar regardless of cause – Wall is distended by fluid and gas – Distension reduces movement of water and ions from lumen to blood ~8 Liters secreted into GI tract each day Vomiting and intestinal secretion result in fluid and electrolyte loss – Shock due to reduced ECF volume – Continued distension results in viscous cycle of decreased fluid absorption and increased secretion – Local effects include ischemia and increased permeability due to necrosis resulting in absorption of bacterial toxins into peritoneal cavity and systemic circulation

146. Intestinal obstruction Signs and symptoms – Cardinal symptoms Abdominal distension Pain Vomiting Absolute constipation – Abdominal radiograph essential for diagnosis

147. Intestinal obstruction Treatment – Correct fluid and electrolyte imbalance – Relieve distention and vomiting by intubation and decompression – Control peritonitis and shock – Remove obstruction – Small bowel obstruction more serious and rapid than colonic Mortality for non strangulation 5-8% if surgical intervention is soon enough Delay or development of strangulation or other complications raises mortality to 35-45%

148. Disorders of the GI tract Intestinal Disorders, continued – Colon cancer - one of the most common types in the US - usually adenocarcinomas that arise from the mucosal lining. Occurrence is equal in the sexes, however, rectal cancer is greater in men than women. Early detection is afforded with fecal occult blood testing and sigmoidoscopy

149. Disorders of the GI tract Liver Disorders – Hepatitis - inflammation of the liver by drugs, alcohol or infection A - transmitted in fecal matter; rarely fatal; infection affords life- long immunity; Vaccine available B - transmitted by direct exchange of blood or body fluids; Vaccine available C - primarily transmitted by direct exchange of blood; sexual transmission can occur, but limited D - transmitted by direct exchange of blood, only in concert with HepB infection E - transmitted by fecal contamination of water

150. Disorders of the GI tract Liver Disorders, continued – Cirrhosis - chronic disease in which active liver cells are replaced by inactive connective tissue; most common cause is alcoholism compounded with malnutrition. In later stages there is hampering of portal circulation causing congestion in the peritoneal cavity - ascites – Cancer - the liver is a common site for metastases

151. Disorders of the GI tract Liver Disorders, continued – Jaundice - yellow coloring of the skin and eyes; cause is damage to the liver making it unable to conjugate bilirubin or a blockage in the bile ducts with bile pigment accumulation in the blood

152. Disorders of the GI tract Gallbladder – Gall stones (cholelithiasis) - formed from cholesterol and block the ducts; pain occurs when the stones prevent the flow of bile and hamper the digestive process – Cholecystitis - Inflammation of the gall bladder

153. Disorders of the GI tract Pancreas – Pancreatitis - inflammation of the pancreas caused by blockage of the bile ducts causing the pancreatic enzymes to back up into the gland which causes destruction of the tissue; another cause is infection of the pancreas.

154. Disorders of the GI tract Digestive Disorders – Anorexia - chronic loss of appetite; causes can be physical (heavy exercise) or mental (more likely to be emotional and/or social rather than physiological disruption in the brain). Anorexia nervosa affects mostly young women – Bulimia (binge-purge syndrome) - prevention of the absorption of food because of induce vomiting or large doses of laxatives

155. Overall lessons: The large intestine functions to store symbionts, absorb water, vitamins, wastes, and toxins. The large intestine has no villi, but does have a folded epithelium. The cecum does most of the water resorption. The colon moves contents along by peristalsis. Defecation is mainly autonomic except for the final step. Many nutrients are absorbed via cotransport with ions. Na + must be pumped out of cells actively. The brush border has enzymes which break down polysaccharides & peptides into monomers before absorption. Water is absorbed by passive osmosis. Lipids are absorbed through membrane & exocytosed to lacteal.

157. Thank You

158. Muntah (Vomitus)

159. Pancreas

160. Pengaturan sekresi pancreas

161. Fungsi Hati

162. Hepar & Fesica Vellea

163. Pengaturan sekresi empedu

164. Usus Halus