Gastrointestinal Physiology 3 PDF

PHYSIOLOGY GASTROINTESTINAL PHYSIOLOGY III UNIVERSITY OF SANTO TOMAS - FACULTY OF MEDICINE AND SURGERY UNIT 3 | SHIFT 4 | TERM 2 | A.Y. 2023-2024 | Lecturer: Dr. Elaine C. Cunanan ◆ C02.1 General Pri...

PHYSIOLOGY GASTROINTESTINAL PHYSIOLOGY III UNIVERSITY OF SANTO TOMAS - FACULTY OF MEDICINE AND SURGERY UNIT 3 | SHIFT 4 | TERM 2 | A.Y. 2023-2024 | Lecturer: Dr. Elaine C. Cunanan ◆ C02.1 General Principles UNIT 02 | GASTROINTESTINAL SECRETIONS, ◆ C02.2 Carbohydrates DIGESTION & ABSORPTION C02.2.1 Carbohydrate Digestion C02.2.2 Carbohydrate Absorption C02.2.3 Clinical Correlates TABLE OF CONTENTS ◆ C02.3 Proteins ➔ C01. Gastrointestinal Secretions C02.2.1 Protein Digestion ◆ C01.1 Alimentary Glands C02.2.2 Protein Absorption C01.1.1 Generalities ◆ C02.4 Fats C01.1.2 Types of Alimentary Glands C02.3.1 Fat Digestion C01.1.3 Stimuli for Secretion C02.3.2 Fat Absorption C01.1.4 Autonomic Nervous Control of C02.3.3 Clinical Correlates Glandular Secretion ◆ C02.5 Absorption ◆ C01.2 Saliva C02.4.1 Absorption of the Gastrointestinal C01.2.1 Type of Salivary Glands Tract C01.2.2 Stages of Saliva Secretii C02.4.2 Absorption of Water C01.2.3 Saliva vs Plasma C01.2.4 Resting vs Maximal Flow 📖 C02.4.3 Absorption of Ions ➔ C0.3 Summary 📖📖 C01.2.5 Regulation of Salivary Secretion ◆ C01.3 Esophagus ➔ References ◆ C01.4 Stomach C01. GASTROINTESTINAL SECRETIONS C01.4.1 Oxyntic Glands & Secretions C01.4.2 Gastric Alkaline Barrier C01.1 Alimentary Glands C01.4.3 Gastric Juice C01.4.4 Pyloric Glands & Secretions C01.1.1 Generalities of Alimentary Glands C01.4.5 Control of Pepsinogen Secretion ➔ Majority of the ducts in the GI system are exocrine C01.4.6 Gastric Acid Secretion ducts C01.4.7 Gastric Secretion During ◆ Possess ducts that open into a certain space, Interdigestive “Fasting” Period as opposed to endocrine glands ◆ C01.5 Pancreas ◆ Endocrine glands do not have ducts – C01.5.1 Pancreatic Enzymes instead, they release hormones into the C01.5.2 Bicarbonate & Water Secretion bloodstream C01.5.3 Hormones that Stimulate Pancreatic Secretions C01.1.2 Types of Alimentary Glands C01.5.4 Phases of Pancreatic Secretions 1. Mucous Glands or Goblet Cells ◆ C01.6 Small Intestines ◆ Single cells, epithelium C01.6.1 Duodenal Brenner’s Glands 2. Pits / Specialized Secretory Cells C01.6.2 Crypts of Liberkuhn ◆ Invaginations of the epithelium into C01.6.3 Small Intestinal Enzymes submucosa C01.6.4 Regulation of Small Intestinal ◆ Ex: Crypts Lieberkuhn (in the small intestine) Secretion 3. Deep Tubular Glands ◆ C01.7 Large Intestines ◆ Located in the stomach and upper duodenum ◆ C01.8 Biliary System ◆ Ex: Parietal Oxyntic Glands C01.8.1 Bile Acid Synthesis 4. Complex / Compound Acinous Glands C01.8.2 Enterohepatic Circulation of Bile ◆ Found in the pancreas, liver, and salivary Acid glands ➔ C02. Digestion and Absorption LEAPMED ‘25 1 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III C01.1.3 Stimuli for Secretion C01.2.1 Types of Salivary Glands ➔ Tactile stimulation (touch) ➔ largest ◆ Happens when the food particles touch the ➔ almost entirely serous wall of the pharynx upon swallowing Parotid ➔ watery secretions contain ➔ Chemical irritation salivary amylase (ptyalin) ➔ Distention of the gut wall ➔ Stimulation of the Autonomic Nervous System Sublingual ➔ mixed secretion ➔ Hormones Submandibular ➔ small Buccal C01.1.4 Autonomic Nervous Control of Glandular ➔ purely mucus Secretion ➔ Parasympathetic Control C01.2.2 Stages of Saliva Secretion ◆ PSHS increases glandular secretion ➔ Saliva secretion is generally understood in two stages: Acini Stage and Salivary Duct Stage GI Region PSNS Innervation CN IX (Glossopharyngeal) Upper GI Tract CN X (Vagus) Jejunum to Proximal Local Neural and Hormonal ⅔ of Large Intestine Stimuli Distal ⅓ of Large Pelvic (Sacral) Nerves Intestine Note: The upper GI tract is generally considered to end at the duodenum. ➔ Sympathetic Control ◆ Dual effect: SNS alone slightly increases secretion When the SNS + PSNS act together, SNS reduces secretion via vasoconstriction C01.2. Saliva ➔ There are generally two types of protein secretion in the saliva: Figure 1.2.2-1: Diagram of a salivary gland divided into ◆ Serous Secretion – contains ptyalin (salivary stages ɑ-amylase) for starch digestion ◆ Mucus Secretion – contains mucin for ➔ Saliva secretion: awake > asleep lubrication and surface protection ➔ The pH of 6.0-7.0 is a favorable range for the ➔ Acini Stage digestive action of ptyalin ◆ Occurs in the acini area of the salivary duct ◆ Involves the Acinar cells of the duct ➔ Functions of Saliva: ◆ Plasma-like levels of ions. It is still isotonic ◆ Lubrication of food at this point. Mucin ◆ Primary secretion containing ptyalin and ◆ Initial digestion of starch mucin Salivary amylase ◆ Neutralization of refluxed acid ➔ Salivary Duct Stage ◆ Maintenance of oral hygiene ◆ Involves the ductal cells Thiocyanate ions ◆ Secondary secretion Lysosomes ◆ Tonicity decreases in this stage due to the Antibodies transport of ions. LEAPMED ‘25 2 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III ◆ Sodium ions are actively reabsorbed via Note: The concentration of bicarbonate in the saliva as the sodium-potassium pump. compared to plasma varies among different sources. Remember that sodium is greater in This table was based on Guyton and Hall’s Textbook of the blood, hence active transport is Physiology. required to push sodium into the blood. Potassium is greater inside the cell, C01.2.4 Resting vs Maximal Flow hence it needs to be actively SALIVA transported into the cell. RESTING MAXIMAL FLOW CONTENT ◆ Chloride ions are passively reabsorbed. Since the pump transports 3 sodium Na+ Lower Higher ions out and only 2 potassium ions in, Cl- Lower Higher the net negativity inside the cell passively drives chloride out (along HCO3- with water). K+ Higher Lower ◆ Potassium ions are actively secreted by Tonicity Hypotonic Less hypotonic the duct cells (into the lumen of the duct). ◆ Bicarbonate ions are secreted in a partly active, partly passive manner via exchange ➔ During maximal flow, ions do not have enough with chloride. time to be transported and reabsorbed, resulting to a change in the ion concentrations of the final saliva. ◆ Formation rate of primary secretion by acini increases up to 20-fold during maximal salivation. ◆ Ductal reconditioning of secretion is considerably reduced due to the high flow rate. C01.2.5 Regulation of Salivary Secretion Salivation is increased due to: ➔ Parasympathetic innervation (major factor) ➔ Sympathetic (minor, less water) ➔ Blood supply to the glands ◆ Kallikrein, bradykinin – vasodilators Figure 1.2.2-2: Diagram of the ion movements in and out of the salivary gland cell Note: Refer to the shaded parts and the color-coded description of events C01.2.3 Saliva vs. Plasma FINAL SALIVA PLASMA + Na Lower Higher - Cl Lower Higher - HCO3 Higher Lower K+ Higher Lower Tonicity Lower (hypotonic) Higher (isotonic) pH Higher (alkaline) Lower (neutral) LEAPMED ‘25 3 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III Figure 1.2.5 -1: Parasympathetic nervous regulation of salivary secretion C01.3. Esophagus ➔ Esophagus – serves as a conduit for food to enter from the mouth to the stomach ◆ Entirely mucous secretion from mucous goblet cells ◆ Mainly provides lubrication for swallowing ◆ Mucus in the upper esophagus prevents mucosal excoriation by newly entering food, while mucus near the epigastric junction protects the esophageal wall from gastric acid juices. C01.4 Stomach ➔ Has a lot of glands (with mucus-secreting cells) ➔ Main secretions: ◆ Mucus ◆ HCL ◆ Intrinsic factor ◆ Pepsinogen ◆ Gastrin (Pyloric) TUBULAR GLAND MAINLY FOUND IN Figure 1.4.1-1: Gastric gland from the body of the stomach Oxyntic body and fundus (proximal 80%) CELLS OF THE OXYNTIC GLANDS Pyloric antral portion (distal 20%) CELL SECRETION Mucous Neck Cells Mainly mucus Parietal (Oxyntic) Hydrochloric acid Cells Intrinsic factor Enterochromaffin-like Histamine (ECL) Cells ○ Mainly paracrine smaller ○ Stimulates nearby found near parietal cells to parietal cells secrete HCl Peptic (Chief) Cells Pepsinogen main ○ A protease Figure 1.4-1: Anatomy of the stomach Mucous Neck Cells ○ When secreted, it C01.4.1 Oxyntic Glands & Secretions (M.A.D.T) 📖 small amount is still in an inactive state ○ An inactive form ➔ Main secretions: of pepsin ◆ Pepsinogen (P) ○ Degrades protein ◆ Hydrochloric Acid (H) ◆ Intrinsic Factor (I) The suffix -gen usually ◆ Histamine indicates that the ◆ Mucus substance is in an inactive ➔ Dr. Cunanan’s memory aide: pH-1 = P, H, I state. LEAPMED ‘25 4 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III C01.4.1.1 Parietal (Oxyntic) Cells (M.A.D.T) CLINICAL CORRELATION: ➔ Treating Hyperacidity ◆ Proton Pump Inhibitors (PPIs) Omeprazole Usually ends with “-prazole” ◆ Histamine receptor blockers (H2-specific) H2 receptors in parietal cells trigger HCl production H1 receptors are for allergies and should not be targeted E.g. Cimetidine, Famotidine, Ranitidine ◆ Antacids (Alkaline substances) Milk of magnesia, Magnesium hydroxide, Gaviscon, Kremil-S Figure 1.4.1.1-1: Postulated mechanism for secretion of HCl ➔ Severe vomiting ◆ Can result to electrolyte abnormality ➔ Proton pump / H+–K+ ATPase Pump ◆ Results in metabolic alkalosis (severe ◆ Active transport is needed to maintain HCl situations) concentration in the lumen. Due to loss of HCl ◆ Goal is to make the stomach more acidic by ◆ Induces hypokalemia transporting H+ from inside the cell to the lumen Due to decrease in K+ of the stomach ◆ Note: pH of stomach lumen = 2.0 ◆ Requires active transport since pH in the lumen C01.4.2 Gastric Alkaline Barrier (M.A.D.T) is already very low ➔ Main secretions: ◆ Mainly mucus ◆ Hormone gastrin HCl Production Process ➔ At lumen of the stomach ◆ With HCl; pH=2.0 H2O inside the parietal cell becomes dissociated into ➔ Surface epithelial mucus cells secrete: H+ and OH- in the cytoplasm ◆ Water ↓ ◆ Na+, Cl– (isosmotic to plasma) H+ is taken from the metabolism of the cell. CO2 is also ◆ HCO3– taken from the metabolism of the cell, as well as from ◆ Thick alkaline viscid mucus the blood ➔ Barrier is formed when mucus traps HCO3– ↓ ➔ Feeding induces mucus and HCO3– secretion to CO2 transiently forms carbonic acid when it reacts counter increased HCl production with water. Carbonic anhydrase catalyzes this ↓ Carbonic acid, being unstable, rapidly degrades to H+ and HCO3– ↓ H+ is pumped out to the lumen. ↓ HCO3– will be reabsorbed in the bloodstream to maintain neutrality in exchange for Cl– ↓ Cl– inside can go out to the lumen to form HCl ➔ Gastric Juice contains: H2O, HCl, KCl, small amount of NaCl Figure 1.4.2-1: Gastric epithelial cells ➔ At Alkaline barrier, pH = 7.0 ◆ Due to: HCO3–, mucus and water ◆ Counters gastric juice pH = 2.0 LEAPMED ‘25 5 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III ➔ Clinical correlation: 2. Parietal cells secrete an intrinsic factor that ◆ Problem in alkaline barrier (e.g. stress ulcer) binds to Vit B12 at the duodenum results to gastric ulcer 3. Intrinsic factor shuttles Vit B12 into ileal cells C01.4.3 Gastric Juice (M.A.D.T) Clinical Correlation Gastric Juice Components ➔ Chronic Atrophic Gastritis 1. Water ◆ When stomach’s parietal cells are destroyed 2. Inorganic constituents by anti-parietal cell antibodies ◆ HCl, K+, little Na+ Achlorhydria - lack of stomach acid 3. Organic constituents secretion ◆ Pepsin Leads to chronic atrophic gastritis ◆ Gastric lipase ○ Glands get atrophied because ◆ Intrinsic factor parietal cells are destroyed ↑ Secretion after a meal Vit B12 deficiency C01.4.3.1 Organic Constituents (M.A.D.T) ➔ Pernicious anemia ➔ Pepsin ◆ Subtype of megaloblastic anemia due to lack ◆ Main organic constituent of Vit B12 absorption and lack of intrinsic ◆ Pepsinogen - inactive proenzyme secreted factor by chief cells. ◆ Megaloblastic or macrocytic anemia - can Activated by stomach acidity be due to either Vit B12 or folic acid deficiency (active at pH ≤ 3; inactive at pH RBCs get smaller as they mature ≥ 5) Incomplete RBC maturation = large ◆ A protease can digest up to 20% of protein RBCs with nucleus ◆ Not mandatory for protein digestion (pancreas also has proteases) C01.4.4 Pyloric Glands & Secretions (M.A.D.T) ◆ Main proteins for digestion are found in the ➔ Pyloric Glands small intestine ◆ DIstal 20% of stomach in antrum ◆ Mostly mucus cells, few peptic cells, almost no ➔ Gastric Lipase parietal cells ◆ From chief cells ◆ Secretions ◆ Digestion of fats Thin mucus (a lot) ◆ Not mandatory for digestion (pancrease also Gastrin (main) - produced by G cells has lipases) ○ Endocrine factor (hormone) ○ Triggered by protein intake ➔ Intrinsic Factor ○ Stimulates HCl production by ◆ From the stomach parietal cells ◆ Produced by parietal cells Small amount of pepsinogen ◆ Requirement for Vitamin B12 (cobalamin) absorption in ileum C01.4.5 Control of Pepsinogen Secretion (M.A.D.T) Vit B12 is needed for erythrocyte (RBC) maturation; important for nerve function ◆ Ileum - main area for Vit B12 absorption Figure 1.4.5-1: Autonomic nervous system activation of gastric hormone release How Intrinsic Factor Helps: Pepsinogen Secretion Stimulated by: 1. Meat is digested, releasing Vit B12 (cobalamin) ➔ Acetylcholine (Ach) LEAPMED ‘25 6 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III ➔ HCl (positive feedback) ◆ Result of gastric acid secretion mechanism (below) C01.4.6 Gastric Acid Secretion (C.J.L.S) C01.4.6.1 Control of Gastric Acid Secretion ➔ Three main substances controlling gastric acid secretion: HISTAMINE Figure 1.4.6.1-1: Diagram of the Control of Gastric Acid ➔ Produced by enterochromaffin-like cells (ECL Secretion cells) ➔ Stimulated by ACh and Gastrin C01.4.6.2 Phases of Gastric Acid Secretion ➔ Paracrine ➔ There are three phases of gastric acid secretion: 1. Cephalic Phase Target Cell Secretion ~30% of HCl production At the sign, smell, thought, or taste of Parietal (oxyntic) cells HCl food, neurotransmitters are elicited from the parasympathetic nervous system, ACETYLCHOLINE particularly by the vagus nerves 2. Gastric Phase ➔ Neurotransmitter released by parasympathetic ~60% of HCl production neurons Occurs once the bolus reaches the ➔ Neural/neurocrine stomach Majority of HCl production is found here Target Cell Secretion In this phase, the stimuli are local nervous secretory reflexes, vagal reflexes, and Parietal (oxyntic) cells HCl gastrin-histamine stimulation 3. Intestinal Phase Peptic cells Pepsinogen ~10% of HCl production Stimulated by nervous mechanisms & Mucous cells Mucous hormonal mechanisms 📖 ECL cells Histamine Occurs once the chyme reaches the small intestines GASTRIN ➔ Hormone produced by G cells in the pyloric C01.4.6.3 Inhibition of Gastric Acid Secretion antrum ➔ Reverse Enterogastric Reflex ➔ Stimulated by protein digestion ◆ Entero = intestine, gastric = stomach ➔ Hormonal/endocrine (travels via the ◆ Stimulated by the presence of food in the bloodstream) small intestine (“negative feedback”) ◆ Transmitted via: Target Cell Secretion Myenteric nervous system Extrinsic sympathetic Parietal (oxyntic) cells HCl Vagus nerve ◆ Brought about by: ECL cells Histamine Small intestinal distension Presence of acid in the duodenum Presence of protein breakdown products Remember: H A G stimulates the cells that produce HCl Irritation of intestinal mucosa ◆ Effect: Slows stomach emptying when intestines are already filled LEAPMED ‘25 7 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III ➔ Intestinal Hormones C01.5.1 Pancreatic Enzymes (C.J.L.S) ◆ The hormones that inhibit gastric acid Note: -gen suffix means that it is an inactive enzyme secretion, which are found in the small intestine, are: PROTEIN DIGESTION Secretin ○ S for stop (or inhibit) Splits proteins into ○ Main inhibitor peptides but does not ○ “Secretes” water and bicarbonate Trypsinogen cause the release of ions to protect the duodenum ↓ individual amino acids against HCl Trypsin Glucose-dependent Insulinotropic Activated by enterokinase Peptide (Gastric Inhibitory Peptide) (Most abundant) secreted by the intestinal ○ GIP = Inhibitory mucosa in contact with ○ Serves also in enhancing insulin chyme secretion Vasoactive Intestinal Polypeptide Splits proteins into ○ VIP = Inhibitory peptides but does not Somatostatin Chymotrypsinogen cause the individual ○ S for stop (or inhibit) ↓ release of individual ○ soma = growth, statin = stop Chymotrypsin amino acids ○ Hormone initially found in the hypothalamus inhibiting growth Activated by trypsin hormone, but was found to be secreted in the pancreas as well Procarboxyl- Splits peptides into amino ◆ Endocrine function in polypeptidase acids pancreas: inhibits insulin and ↓ glucagon ○ Also found in the antrum 📖 Carboxypolypeptidase Activated by trypsin CARBOHYDRATE DIGESTION Remember: S S GIP VIP inhibit HCl production ➔ VIP JEEPS → VIP GIP S S Hydrolyzes starch, glycogen, and other C01.4.7 Gastric Secretion During Interdigestive carbohydrates (except “Fasting” Period (C.J.L.S) cellulose/fiber) into ➔ Secretion is almost entirely of non-oxyntic type: disaccharides and ◆ Mainly mucus Pancreatic amylase trisaccharides ◆ Little pepsin ◆ Almost no acid Doc Cunanan (2024): ➔ Emotional stimuli may trigger release of cellulose/fiber serves as pepsinogen and HCl (similar to cephalic phase) a prebiotic in the colon ◆ Reason why stressful situations can cause peptic ulcers FAT DIGESTION ➔ Hyperacidity can also be caused even without food due to cephalic stimuli Hydrolyzes fat into fatty Pancreatic lipase acids and C01.5 PANCREAS (C.J.L.S.) monoglycerides ➔ Pancreas has endocrine and exocrine parts Hydrolyzes cholesterol ◆ Exocrine: glands with ducts Cholesterol esterase esters ◆ Focus is on the exocrine pancreas ➔ Pancreatic acinar cells secrete pancreatic Phospholipase Hydrolyzes phospholipids enzymes into fatty acids ➔ Pancreatic duct/ductule epithelial cells secrete water and HCO3– (neutralizes the acid from the stomach) LEAPMED ‘25 8 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III ➔ Protein Digestion 4. H+ ions are reabsorbed. Na+ and water are ◆ When the enzymes are first synthesized, they passively reabsorbed into the lumen. are in their inactive forms. They are activated 5. Movement of Na+ and HCO3– creates an after being secreted into the duodenum. osmotic pressure gradient that causes ◆ While secreting pancreatic enzymes, acinar osmosis of water into the pancreatic duct. cells simultaneously secrete trypsin inhibitors ◆ The main electrolyte needed in the as well, which prevents pancreatic pancreatic duct is bicarbonate (HCO3–) autodigestion by neutralizing the remaining trypsin (negative feedback) It prevents the activation of trypsin and other enzymes while still in the pancreas “You don’t want too much enzymes because the enzymes may destroy the pancreas itself” ➔ Clinical Correlate: Acute Pancreatitis ◆ When the pancreas is severely damaged or a duct is blocked (i.e., gallstones), pancreatic secretion becomes pooled and overwhelms the trypsin inhibitor Pancreatic secretions become activated and can digest the entire pancreas within a few hours ◆ Other causes: chronic alcoholism, Figure 1.5.2. Bicarbonate & Water Secretion hypertriglyceridemia, and hypercalcemia ◆ If you have a patient coming in with stomach ache, and you are thinking of possible C01.5.3 Hormones that Stimulate Pancreatic pancreatitis, you can request for serum lipase Secretions (Y.B.V.S) and serum amylase If their values are high, this means it Acetylcholine comes from the pancreas, thus the patient has pancreatitis Secreted by parasympathetic vagus and cholinergic 📖 Note: Removal of the pancreas is compatible with life, but patients who undergo pancreatectomy will have nerves in enteric nervous system Stimulates pancreatic problems with digestion afterwards. The risk of diabetes enzyme secretion by acini also increases as it is the pancreas that secretes insulin. As a result, they are given insulin and enzymes to Cholecystokinin (CCK) compensate for the removal of the pancreas. C01.5.2 Bicarbonate & Water Secretion 📖 ➔ Pancreatic Duct / Ductule Epithelial Cells (C.J.L.S) Secreted by I cells of duodenal and upper jejunal mucosa ◆ Produce water via osmosis and create HCO3– Stimulated by proteases, Stimulates pancreatic to neutralize the acid from the stomach peptones, long-chain fatty enzyme secretion by acini ◆ Isosmotic bicarbonate secretion acids in food ◆ Process: 1. CO2 can freely enter the pancreatic duct Secretin cells and, under the influence of carbonic anhydrase, combines with water to form Secreted by S cells of duodenum and upper jejunal carbonic acid (H2CO3) mucosa 2. H2CO3 dissociates into HCO3– and H+ ions 3. H+ ions go back out into the bloodstream. Stimulated by HCl in food Stimulates HCO3- and HCO3– is secreted into the lumen in water secretion by ducts exchange for Cl– by secondary active transport. LEAPMED ‘25 9 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III Multiplicative Effects of Different Stimuli 📑 ➔ When all the hormonal stimuli occur at once, the ➔ HCl stimulates secretin thus, sodium and bicarbonate are the highest and there is less of the total secretion is greater than the sum of enzyme secretions caused by each one separately ➔ Peptone (protein) stimulates CCK which in turn ➔ Pancreatic secretion results from combined effects stimulates pancreatic acinar enzyme secretion of multiple stimuli ➔ Soap aka fat, stimulates both secretin and CCK C01.5.4 Phases of Pancreatic Secretion (Y.B.V.S) C01.6. SMALL INTESTINES (Y.B.V.S) Cephalic Phase ➔ Brain signals cause ACh release → pancreatic C01.6.1 Duodenal Brunner’s Glands (Y.B.V.S) acini enzyme release ➔ Compound mucus glands ➔ 20% of total pancreatic enzyme secretion after a ➔ Located between pylorus of stomach and papilla meal of Vater ➔ Small amounts of water and electrolytes ◆ Where pancreatic secretion and bile empty ➔ The reason why pancreas also has cephalic phase into duodenum is because when you see, taste, or think of food, ➔ Secrete large amounts of alkaline mucus (contains the body already primes you for food HCO3-) in response to ◆ Irritating stimuli on the duodenal mucosa Gastric Phase ◆ Vagal stimulation ➔ Nervous stimulation of enzyme secretion ◆ GI hormones (especially secretin) continues ➔ Protect duodenal wall from acid digestion ➔ 5-10% of pancreatic enzymes secreted after a ➔ Inhibited by sympathetic stimulation meal ◆ Stressed individuals can develop ➔ Lack of significant fluid secretion peptic/duodenal ulcers ➔ While the food is still in the stomach, you already stimulate the pancreas C01.6.2 Crypts of Lieberkühn (Y.B.V.S) ➔ Entire surface of the SI between the intestinal villi Intestinal Phase ➔ Epithelium composed of two types of cells: ➔ After chyme leaves the stomach and enters the ◆ Goblet cells - secrete mucus intestine ◆ Enterocytes - secretes large quantities of ➔ Duodenal/upper jejunal S Cells → secretin; water and electrolytes and reabsorbs them Duodenal/upper jejunal I cells → CCK along with end-products of digestion ➔ Secretin release (HCl in Food) → copious ➔ Two active secretory processes pancreatic secretion ◆ Active secretion of Cl- into the crypts ➔ CCK release (peptones, proteoses, LCFA) → ◆ Active secretion of HCO3- 70%-80% of total pancreatic enzyme secretion Passive drag of Na+ after a meal Passive osmotic movement of water ➔ pH of 7-8 (alkaline): pancreatic enzyme functions optimally ◆ Neutral to basic pH to become activated C01.6.3 Small Intestinal Enzymes (Y.B.V.S) Brush Border Enzymes Substances that Stimulate Pancreatic Secretion: Peptides Small peptides → amino acids Sucrase, Maltase, Disaccharides → Isomaltase, Lactase monosaccharides Intestinal Lipase Neutral fats → glycerol & (small amounts) fatty acids Figure 1.5.4-1: 📖 Rate of pancreatic secretions LEAPMED ‘25 10 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III C01.6.4 Regulation of Small Intestinal Secretion LENGTH OF THE INTESTINES (Y.B.V.S) ➔ Mainly local regulation Small Intestine Large Intestine ◆ Local enteric nervous reflexes ◆ Initiated by tactile/irritative stimuli from the 3-5 meters 1.5 meters chyme in the intestines 10-16 feet 5 feet C01.7 LARGE INTESTINES (Y.B.V.S) ➔ The surface area of the small intestine roughly ➔ Mucosa contains no villi (main difference between averages to 250 m2 small and large intestines) ➔ The increase in the surface area of the small intestines is because of its modifications, the Mucosal Secretions foldings. ➔ Epithelial cells DO NOT secrete digestive ◆ Folds of Kerckring (valvulae enzymes (digestion does not take place in the conniventes/ plicae circularis), villi, and large intestines) microvilli increase the mucosal absorptive ➔ Crypts of Lieberkühn area by nearly 1000-fold ◆ Mucus cells secrete mucus ◆ Non-mucus cells amounts of HCO3- secrete moderate C02.2 CARBOHYDRATES 📑 DIETARY SOURCES OF CARBOHYDRATES Regulation of Large Intestinal Secretion ➔ Rate of mucus secretion is regulated by direct Starch Non-animal foods (bread, cereal, pasta, tactile stimulation and by local nervous reflexes rice, potatoes, beans, chestnuts) and pelvic nerves Sucrose Cane sugar Functions of Large Intestinal Secretion Table sugar ➔ Protects the intestinal wall against excoriation and bacteria (as bacteria is prolific in the feces) Lactose Milk ➔ Provides an adherent medium for holding fecal matter together Cellulose Fiber from plant sources (indigestible) ➔ Provides barrier against acid in feces ➔ Goes into the large intestine and enhances the presence of good bacteria C02. DIGESTION AND ABSORPTION ➔ Humans have no enzymes to digest cellulose C02.1 GENERAL PRINCIPLES 📑 C02.2.1 Carbohydrate Digestion Digestion ➔ Process of breaking down food by mechanical and enzymatic action in the alimentary canal into substances that can be used by the body Absorption ➔ Movement of digested food molecules through the walls of the small intestine ◆ If it fails to reach the bloodstream, it means it is not absorbed ➔ The digested food molecules should reach the circulation Figure 2.2.1-1. Digestion Pathway LEAPMED ‘25 11 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III PROCESS: TERMS 1. Salivary amylase will break the polysaccharides into dextrins. Monosaccharides No need to digest ○ Polysaccharides are complex carbohydrates Disaccharides Initially, no need to digest (still, ○ Starch is the main source of complex they must be broken down carbohydrates (glycogen, stored in the further in the process) liver, only exists in a small amount) 2. When the dextrins reach the small intestine Polysaccharides Need to be digested as early as (duodenum), they are further broken down into in the buccal cavity smaller pieces by pancreatic amylase producing maltose, sucrose, and lactose Salivary Amylase Enzyme in the buccal cavity (disaccharides) (ptyalin) 3. At the brush border of the enterocytes, there Dextrins Polymers with 2-3 glucose are disaccharidases that will break down molecules joined together disaccharides into individual units producing glucose, fructose, and galactose Pancreatic Enzyme in the small intestine (monosaccharides) Amylase (duodenum) ○ Only monosaccharides are absorbed in the GI Tract or Small Intestines Disaccharidases Enzymes at the brush border of the enterocytes CARBOHYDRATE DIGESTION ➔ Maltase ➔ Sucrase SITE ENZYME PRODUCTS ➔ Lactase ➔ α-dextrinase Buccal Cavity Salivary Dextrins amylase Maltose glucose + glucose Stomach Destroyed by No Sucrose fructose + glucose acidity carbohydrate digestion Lactose galactose + glucose Small Intestine Pancreatic Disaccharides amylase (maltose, sucrose, lactose) Brush Border Disaccharidases Monosaccharide of Enterocytes (maltase, s (glucose, sucrase, fructose, lactase, galactose) α-dextrinase) Figure 2.2.1-3. Carbohydrate Digestion Figure 2.2.1-2. Digestion of Carbohydrates LEAPMED ‘25 12 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III 1. Starch is first digested in the mouth ○ The mouth contains ptyalin 2. Next, Starch is digested in the duodenum ○ Enzyme: Pancreatic amylase (acts upon the polysaccharides to make them into disaccharides) 3. In the intestine, these disaccharides are further broken down into monosaccharides by the brush border enzymes secreted by the enterocytes ○ Maltose and smaller oligosaccharides (3 to 9 polymers) Enzyme: Maltase and α-dextrinase (break down maltose into glucose) ○ Lactose Enzyme: Lactase (convert lactose Figure 2.2.1-4. Enzymes that Aid Carbohydrate into galactose and glucose) Digestions ○ Sucrose Enzyme: Sucrase (convert sucrose C02.2.2 Carbohydrate Absorption into fructose and glucose) 4. Glucose, galactose, and fructose will eventually be absorbed in the GI tract. Additional Notes: ➔ Most carbohydrate digestion occurs in the duodenum by the pancreatic amylase ◆ [In the mouth] polymers will become shorter polymers and if we are lucky, they will become disaccharides ➔ In the stomach, nothing happens because the salivary amylase is destroyed by the acid ◆ pH = 2.0 to 3.0 ◆ There is no carbohydrate digestion in the stomach ◆ Salivary amylase gets destroyed once it reaches the stomach ➔ The monosaccharides should enter the circulation for it to be called ‘absorbed’ ➔ Only the undigested carbohydrates go to the large intestine ➔ Some of the starch may already become maltose in the mouth Figure 2.2.2-1. Absorption Of Glucose, Galactose, And ◆ That’s why if you chew more slowly, you Fructose Through The Intestinal Epithelium. break them down into smaller particles ◆ Sometimes, you can even taste the ➔ ONLY monosaccharides can get absorbed into sweetness of it the bloodstream ➔ Sodium-Potassium ATPase (Sodium-Potassium Pump): primary active transporter ◆ Found along the basolateral membrane or beside the blood Carbohydrate Absorption involves the following: ➔ ATP: Adenosine Triphosphate ➔ GLUT2: Glucose transporter 2 ➔ GLUT5: Glucose transporter 5 ➔ SGLT1: Sodium-Glucose Co-Transporter 1 LEAPMED ‘25 13 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III C02.2.2.1 From Intestine Lumen to Cells ➔ The intestinal lumen is where the food goes, gets digested and become monosaccharides ➔ Glucose and galactose will enter using the Sodium-Glucose Co-Transporter 1 (SGLT1) via secondary active transport ◆ SGLT1 is a secondary active transporter because it derives its energy from the primary active transporter, Na+-K+ Pump Figure 2.2.2-2. Oral Rehydration Therapy ◆ Sodium enters, and this drives Glucose to also enter Can improve hydration status of patient who is ◆ Also called a symporter because losing a lot of fluid due to diarrhea Sodium and Glucose enter in the same ○ This is because there is mass excretion direction of water in patients with diarrhea ➔ We don’t have energy here [secondary active ○ There is a need to replenish the loss of transport] because of the primary active fluids transport [Na+ -K+ Pump] Oral rehydration solution ◆ Normally, Na+ is 140 mEq intracellularly ○ Presence of Sodium and Glucose ◆ If you pump it out, the cell will have only creates an osmotic gradient 50 mEq or 50 mmol of Na+ ○ This is because sodium and glucose ◆ This very low value will favor influx of enter at the same time Na+ from the lumen ○ Due to the osmotic gradient, one is ◆ As Na+ enters, glucose enters with it; drawing water within hence, co-transporter Intravenous (IV) fluid is given if the person ➔ Fructose enters using Glucose Transporter 5 cannot ingest fluid (GLUT5) via facilitated diffusion ○ Intractable vomiting ◆ Fructose CANNOT enter via SGLT1 ○ Intestinal obstruction ◆ Remember: (FFF) Fructose, Facilitated ○ Dehydration is too severe diffusion, Glucose Transporter Five ○ There is need to rest the alimentary tract C02.2.2.2 From Cells to Paracellular Space ➔ All three of them should go to the blood C02.3 PROTEINS 📑 (J.G.C.L.) ➔ Dietary proteins- chemically long chains of circulation amino acids bound together by peptide ➔ ALL monosaccharides will enter using the linkages Glucose Transporter 2 (GLUT2) via facilitated ➔ Characterized by the types and sequential diffusion arrangements of amino acids present in the ◆ Also found in the basolateral membrane protein molecule (towards the interstitium) ➔ Most proteins enter the cell as dipeptide or ◆ Where the monosaccharides exit from tripeptide the cell into the interstitium and back ➔ Only minimal amount will enter as individual into the blood amino acids C02.2.3 Clinical Correlates 📑 ➔ Once inside the cell, tripeptides will be acted upon by tripeptidase to be broken down into individual amino acids unlike glucose and Case 1 carbohydrates Oral rehydration therapy is an effective way of ➔ Glucose and carbohydrates are broken down to rehydration in diarrheal illness. Oral rehydration solution individual units at brush border before they is essentially just water, salt, and glucose. enter the cell LEAPMED ‘25 14 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III Figure 2.3.1-2: Diagram of Protein Digestion (Berne & Figure 2.3-1: Diagram of Protein Digestion Levy) ➔ At the intestinal lining, the absorption is practically the same as carbohydrates/sugars - co-transport or secondary active transport system C02.3.1 Protein Digestion ➔ No protein digestion in the mouth ➔ “Of course in the mouth we chew it so we can say it is a form of mechanical digestion, but enzymatic digestion starts in the stomach” (Cunanan, 2023) ➔ Protein digestion begins in the stomach through pepsin 📑 Figure 2.3.1-3: Diagram of Protein Digestion, Showing the Organ Setting of Each Process ( , Guyton & Hall) Figure 2.3.1-1. Schematic Diagram of Protein Digestion LEAPMED ‘25 15 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III ◆ Erepsin (a protease enzyme) found in the intestinal juices secreted at the ileum and from the pancreas ➔ Denatured and partially hydrolyzed proteins are further broken down into small peptides and amino acids. ◆ Oligopeptides can either be broken down into two or three amino acids in a chain. Some can even be broken down into single amino acids It is preferential for the oligopeptides to be broken down into either single amino acids or two amino acid chains. ◆ These amino acid chains can then enter the cell for further digestion ➔ Products are: ◆ 80% dipeptides and tripeptides ◆ 20% amino acids Figure 2.3.1-4. 📑 Diagram of Protein Digestion C02.3.1.3 In the Enterocytes ➔ Enzyme: Peptidases C02.3.1.1 In the Stomach ◆ Brush border enzymes ➔ Enzyme: Pepsin ◆ Important peptidases are: ◆ Active at pH of 2.0-3.0 and is inactive at aminopeptidase a pH of 5.0 several dipeptidases ◆ Can digest collagen, a major ◆ Split large polypeptides into: constituent of intercellular connective Dipeptides tissue of meats Tripeptides ◆ Produced by the chief cells of oxyntic single amino acids glands ◆ Converts proteins into proteoses, ➔ Site of final digestion peptones and polypeptides ➔ Most of the proteins enter the cell as either ➔ Acidic pH of the stomach activates pepsin dipeptides or tripeptides ◆ HCl, which has a pH of around 0.8, ◆ Dipeptides → acted upon by mixes with the stomach contents and dipeptidase the non-oxyntic glandular secretions ◆ Tripeptides → acted upon by ◆ This makes the average stomach pH tripeptidase around 2.0-3.0, which is a favorable ➔ Proteins are broken down into single amino range of acidity for pepsin activity acids ➔ Partial digestion ➔ Digestion produces: ◆ Pepsin provides only 10% to 20% ◆ 90% amino acids protein digestion ◆ 10% dipeptides and tripeptides ◆ Hydrolytic process at the peptide ➔ Products are then actively transported to the linkages between amino acids bloodstream for absorption ➔ Dietary proteins are broken down into denatured and partially hydrolyzed proteins (polypeptides) PROTEIN DIGESTION C02.3.1.2 In the Duodenum and Jejunum Site Enzyme Process ➔ Enzymes: Trypsin, Chymotrypsin, Aminopeptidase, Carboxypolypeptidase, Stomach Pepsin Protein → Elastase Polypeptides, ◆ Trypsin at the duodenum Proteoses & ◆ Elastase is responsible for digesting Peptones elastin LEAPMED ‘25 16 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III ➔ Bile salts act as a “ferry” that brings the micelles Duodenum and Trypsin (by Polypeptides → to the brush border Jejunum pancreas) Peptides Small Intestine Erepsin Peptides → Amino acids NOTE: According to external sources[1,2], dipeptidases and tripeptidases were formerly called erepsin. Erepsin is secreted by the intestinal glands in the ileum and the pancreas. However, it is also widely found in other cells. The term erepsin is less used nowadays as more specific terms (like dipeptidase and tripeptidase) are preferred. Figure 2.4.1-1: Diagram of Lipid Digestion C02.3.2 Protein Absorption ➔ Small peptides and amino acids are absorbed C02.4.1.1 In the Stomach through a co-transport system (secondary active ➔ Digested by lingual lipase from lingual glands transport) ➔ Digested less than 10% of fat ◆ 10 different types of transport proteins are used to transfer the proteins from C02.4.1.2 In the Duodenum the intestinal lumen to the cell interior 1. Emulsification – Bile salts and lecithin from the ◆ Secondary active transport via Na+ - liver break down large fat globules (lipids) into Amino Acids transporter smaller lipids (emulsion droplets) ➔ Transportation to the paracellular space (to the 2. The smaller emulsified droplets can be digested circulation) is through facilitated diffusion by pancreatic lipase into 2-monoglycerides and free fatty acids, as well as bile salts. Other pancreatic lipases are: a. Cholesterol ester hydrolase - digests cholesterol esters into free cholesterol and free fatty acids b. Phospholipase A2 - breaks down phospholipids 3. Bile salts hold the monoglycerides and free fatty acids together, forming micelles, ready to be absorbed. Figure 2.3.2-1. Diagram of Protein Absorption through secondary active transport C02.4 FATS (A.L.F.) ➔ Most common type of fat in the diet are triglycerides ➔ Cholesterol doesn’t contain fatty acids, but is considered a lipid nonetheless Figure 2.4.1-1: Diagram of Fat Digestion (Guyton & Hall) C02.4.1 Fat Digestion ➔ Large fat molecules (fat globules) acted on by bile salts break them down into smaller lipids (emulsion droplets) ➔ Lipases can digest smaller lipids into 2-monoglycerides and fatty acids + bile salts ➔ Free fatty acids form micelles (free fatty acids + bile salts) LEAPMED ‘25 17 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III C02.4.2 Fat Absorption ◆ Triglycerides enter the endoplasmic reticulum of the enterocyte and combine with phospholipase, cholesterol, and apolipoprotein to form chylomicrons ◆ Chylomicrons are transported via secretory vesicles to the interstitial space, then into the lacteals to reach the lymphatic system before going into circulation ◆ It is through the thoracic duct that the chylomicrons enter the bloodstream ➔ Transported through diffusion Figure 2.4.2-1: Diagram of Fat Absorption C02.4.3 Clinical Correlates Case 2 C02.4.2.1 In the Small Intestine ➔ A 35-year-old female self-medicated with Orlistat ➔ Absorption occurs at the brush border of the (lingual and pancreatic lipase inhibitor). Two small intestine enterocytes weeks later, she is happy to inform everyone ◆ Mostly occurs in the duodenum that she lost 5 kg body weight. ➔ Bile salts in the micelles allow the fats to enter ◆ Steatorrhea the enterocytes steato = “fat”; rrhea = “flow, ◆ Bile salts “ferry” the free fatty acids, free discharge” cholesterols, monoglycerides and Refers to fat in stool phospholipid digestates into the brush Occurs when fat from food is not border of the enterocytes digested and could not be ◆ Bile salts remain in the small intestine absorbed, and is therefore lumen, ready to ferry other lipid passed through the alimentary molecules again tract as excrement. Caused by the inhibition of C02.4.2.1 In the Enterocytes lipase ➔ Short-chain fatty acids (an medium-chain) are ○ In the case, the drug directly absorbed into the blood circulation orlistat caused the through capillaries inhibition of lipase → ➔ Long-chain fatty acids and monoglycerides excretion of fat in the combine again inside the enterocyte to form stool → weight loss. triglycerides SUMMARY TABLE: DIGESTION AND ABSORPTION Parameters Carbohydrates Proteins Fats Initial site of Mouth Stomach Stomach digestion Enzyme Salivary amylase (ptyalin) Pepsin Lingual lipase Disaccharide maltose + Polypeptides, proteoses**, Product LI. ** Almost all nutrients will be absorbed in the SI. ◆ Aldosterone Needed for the absorption of water such that only 100 mL of the 1.5 L of fluid from the SI will be excreted in the feces ◆ Cl––HCO3– Exchanger Neutralizes the acid produced by bacteria ➔ Distal Half – “Storage colon” Figure 2.5.3-1: Diagram of Ion Absorption ◆ Where feces are stored C02.5.3.1 Sodium Ion C02.5.2 Absorption of Water ➔ Sodium absorption is powered by the active ➔ Water is transported through the intestinal transport of sodium from inside the epithelial membrane entirely by diffusion, obeying the laws cells through the basal and lateral walls into of osmosis. paracellular spaces ➔ Regardless of whether it is transcellular or ➔ Also co-transported (secondary active transport) paracellular, since sodium, amino acids, and through the brush border membrane by specific glucose are absorbed, they are osmotic carrier proteins: substances, so they would cause the absorption ◆ Sodium-glucose co-transporter 1 of water. (SGLT1) ◆ Sodium-amino acids co-transporters ◆ Sodium-hydrogen exchanger TRANSCELLULAR PARACELLULAR ➔ Aldosterone has an effect in both the kidney and ABSORPTION ABSORPTION intestine (GIT) ◆ Aldosterone will favor the absorption of Passes through cells Passes between cells sodium in the intestine → water follows ◆ Aldosterone can stimulate the active Na+ and glucose enter The area (between the transport of sodium LEAPMED ‘25 20 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III ◆ ↑ sodium absorption = ↑ Cl– and H2O have been secreted from the pancreas and absorption (direct relationship) bile. ◆ Increased activation of the enzymes ➔ In the Ileum and Large Intestine caused by aldosterone will manifest in ◆ Epithelial cells on the surface of the villi 1-3 hours have the capability of secreting HCO3– in ➔ In the colon: no NaCl loss, minimal water loss exchange for the absorption of Cl– ions. (as ◆ ~100 mL of water will go with the feces, mentioned in C02.5.3.2) the rest of 1.5 L will be reabsorbed. ➔ Where Na+ goes, water and Cl– will follow. C02.5.1.4 Other Ions ION METHOD OF ABSORPTION C02.5.3.2 Chloride Ion ➔ In the Upper Part of the Small Intestine Calcium Actively absorbed in the blood ◆ Chloride absorption is rapid and occurs from the duodenum mainly by diffusion Chloride ions move along the Absorption is dependent on electrical gradient “following” the the amount of parathyroid sodium ions hormone and Vitamin D ➔ In the Ileum and Large Intestine ◆ Takes place via Cl––HCO3– exchanger (a Iron Actively absorbed in the small secondary active transporter) in the brush intestine border membrane in the luminal side Degree of absorption of iron ◆ In the basal side, chloride just diffuses into depends on the requirement the blood via chloride channels since there for hemoglobin formation is increased number of chloride inside the cell Potassium, Actively absorbed through the Chloride ions then exit the cells Magnesium, intestinal mucosa through a channel in the basolateral Phosphate membrane Monovalent ions are Occurs since lots of bacteria in the absorbed easily in great large intestine produce acid as they quantities (needed by break down the undigested particles the body in greater amounts) (this is a process of fermentation) → bicarbonate is secreted to neutralize Fortunately, bivalent ions are the acid only needed in small amounts Since a negative charge is lost (Cl–), another negative charge must be monovalent > bivalent brought in return (HCO3–) to maintain electron neutrality C03. SUMMARY C02.5.3.3 Bicarbonate Ion ➔ Active Absorption of HCO3– ◆ H+ ions move out to the lumen while Na+ C03.1 SUMMARY OF CONCEPTS goes inside the cell via Na+– H+ exchanger ➔ The Gastrointestinal Tract possesses numerous ◆ H+ ions that went to the intestinal lumen ducts that have various secretory functions combine with bicarbonate to form carbonic activated by different modalities acid (H2CO3) ◆ Carbonic acid is unstable and rapidly SALIVA dissociates to CO2 and H2O ➔ Serous secretion contains ptyalin (salivary ◆ CO2 enters the cell via diffusion, goes in the amylase) which functions in starch digestion while bloodstream to join the circulation, then is mucous secretion contains mucin which functions expired through the lungs. in lubrication and surface protection ➔ In the Duodenum and Jejunum ➔ The parotid glands exhibit almost entirely serous ◆ Large quantities of bicarbonate ions must secretion, the submandibular and sublingual be reabsorbed because large amounts glands exhibit mixed secretion, while the buccal glands exhibit purely mucous secretion LEAPMED ‘25 21 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III ➔ The Acini stage of secretion involves the Acinar Trypsin Protein digestion cells, primary secretion of ptyalin and mucin, and Chymotrypsin plasma-like ion levels (isotonic) Carboxypolypeptidase ➔ The Salivary Duct stage involves the ductal stage, secondary secretion, and decreased tonicity due Pancreatic Amylase Digestion of carbohydrates to ion transport except cellulose ➔ Plasma exhibits greater NaCl concentration and tonicity while final saliva exhibits greater Pancreatic Lipase Digestion of neutral fats bicarbonate and potassium concentrations and alkalinity Phospholipase Hydrolysis of phospholipids ESOPHAGUS ➔ Esophageal goblet cells secrete mucous for Cholesterol esterase Hydrolysis of cholesterol lubrication during swallowing esters STOMACH ➔ The PROXIMAL 80% of the stomach secretes ➔ Pancreatic duct epithelial cells secrete water and HCl, Intrinsic Factor, and Pepsinogen (H-I-P) while bicarbonate which are important for neutralizing the DISTAL 20% of the stomach secretes gastrin the acid coming from the stomach ➔ Oxyntic glands contain different types of of cells ➔ ACh and CCK stimulate the secretion of including: pancreatic enzymes by the acinar cells ➔ Secretin stimulates the secretion of water and HCO3- by the ductule cells Mucous Neck cells Mucous secretion Parietal (Oxyntic) HCl and Intrinsic Factor SMALL INTESTINES Cells secretion ➔ Duodenal Brunner’s glands (compound Enterochromaffin-like Paracrine stimulation of mucous glands) (ECL) Cells HCL secretion ◆ Between pylorus of stomach and the papilla of Vater where pancreatic secretions and bile Peptic (Chief) Cells Pepsinogen secretion empty into the duodenum ◆ Secrete large amounts of alkaline (HCO3+ ➔ Mucus and gastrin are mainly secreted in the containing) mucous in response to: Gastric Alkaline Barrier (1) Irritating stimuli on the duodenal mucosa (2) Vagal stimulation (3) Gastrointestinal hormones, especially secretin Gastric Hormone/NT/P Hormone/NT/P ◆ Protects duodenal wall fron acidic chime Secretion aracrine aracrine coming from the stomach Stimulator Inhibitor ◆ Inhbited by sympathetic stimulation, thus explaining stress-associated peptic ulcers HCl Acetylcholine, GIP, Secretin, Histamine, and Somatostatin, ➔ Crypts of Lieberkühn Gastrin and VIP (I for ◆ Entire surface of the small intestine between Inhibition and the intestinal villi S for Stop) ◆ Mainly secrete mucus, water, and electrolytes ◆ Epithelium composed of two types of cells Pepsinogen Acetylcholine Goblet cells secretes mucus for lubrication and protection PANCREAS Enterocytes secrete large quantities of ➔ Pancreatic acinar cells secrete the following water and electrolytes and reabsorb pancreatic enzymes: water and electrolytes along with end products of digestion LEAPMED ‘25 22 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III ○ Colera vibrio stimulates the Chief (Peptic) Cells Pepsinogen enterocytes to produce large amounts of water and electrolytes Pyloric Glands Gastrin resulting in diarrhea ○ If the stool is voluminous, then most likely it is an intestinal problem Gastric Hormone/NT/P Hormone/NT/P ◆ Two active secretory processes Production aracrine aracrine (1) Active secretion of Cl- into the crypts Stimulator Inhibitor (2) Active secretion of HCO3- ○ Passive drag of Na+ ions HCl Histamine Secretin ○ Passive osmotic movement of water Acetylcholine Somatostatin ➔ Small Intestinal “Brush-Border” Enzymes Gastrin GIP ◆ Peptidases split proteins into amino acids ◆ Sucrase, maltase, isomaltase, and lactase VIP spit disaccharides into monosaccharides ◆ Intestinal lipase (small amounts) split Pepsinogen Acetylcholine neutral fats into glycerol and fatty acids LARGE INTESTINES Nutrient Digestion Pancreatic Enzyme ➔ Absence of villi and enzymatic degradation Activated ➔ Mainly secretes mucus and HCO3- to protect the intestinal wall from the bacteria in the feces Protein Digestion Trypsin ➔ Rate of mucus secretion is regulated by direct, tactile stimulation and by local nervous reflexes Chymotrypsin and parasympathetic sacral nerves Carboxylpeptidase C03.2 WORKSHEET ANSWERS Carbohydrate Digestion Pancreatic amylase Variable Quantity in FINAL SALIVA (compared to Triglyceride Digestion Pancreatic lipase quantity in PLASMA) Phospholipid Digestion Phospholipase NaCl Lower Cholesterol Digestion Cholesterol esterase HCO3- Higher K+ Higher Pancreatic Hormone/NT/Paracrine Production Stimulator Tonicity Lower Enzymes Acetylcholine pH Higher CCK HCO3- and Water Secretin Gastric Cells/Glands Substance Secreted Gallbladder CCK Parietal (Oxyntic) Cells HCl Contraction Acetylcholine Intrinsic Factor Enterochromaffin-like Histamine (ECL) Cells LEAPMED ‘25 23 PHYSIOLOGY - GASTROINTESTINAL PHYSIOLOGY III C03.3 QUANTITATIVE COMPARISONS 1. Salivary amylase secretion: (1) Buccal glands (2) Parotid glands 2. Saliva tonicity: (1) After acini stage (2) After salivary duct stage 3. Cl- level: (1) Final saliva (2) Plasma 4. Pepsinogen secretion: (1) Distal stomach (2) Proximal stomach 5. Gastrin secretion: (1) Fundus (2) Pylorus 6. Fat digestion: (1) Pancreatic lipase (2) Trypsin 7. Pancreatic secretion: (1) Gastric phase (2) Intestinal Phase 8. Brunner’s glands activity (1) Chronically-stressed individual (2) Normal individual Answer Key: 1. B. 2. A. 3. B. 4. B. 5. B. 6. A. 7. B. 8. B. C03.4 VARIATION RELATIONSHIPS 1. (1) Sympathetic stimulation (2) GI glands secretion 2. (1) Anticholinergic activity (2) Salivary secretion 3. (1) Histamine (2) HCl secretion 4. (1) Vasoactive Intestinal Polypeptide/VIP (2) Gastric acid secretion 5. (1) Biliverdin (2) Trypsin activation 6. (1) Cholecystokinin (2) Pancreatic enzyme secretion 7. (1) HCl (2) Pancreatic enzyme secretion 8. (1) Intestinal lipase activity (2) Glycerol and fatty acids Answer Key: 1. A. 2. B. 3. A. 4. B. 5. C. 6. A. B. 7. B. 8. A. LEAPMED ‘25 24