Physiology Secretion PDF

24 M. k. Handout Sama shannak Yaman mahmoud Mohammed Khatatbeh  GASTROINTESTINAL SECRETION Secretions along digestive system appear as a response to the presence of food in GI tract. The composition of secretions (enzymes and other constituents) varies according to the ty...

24 M. k. Handout Sama shannak Yaman mahmoud Mohammed Khatatbeh  GASTROINTESTINAL SECRETION Secretions along digestive system appear as a response to the presence of food in GI tract. The composition of secretions (enzymes and other constituents) varies according to the type of food, and serves to: Digest food. Lubricate and protect the mucosa. The secretion process in the gastrointestinal (GI) tract involves: Composition of Secretions: 1. Organic Materials: Synthesized by secretory cells. Stored in vesicles and secreted upon stimulation. 2. Water and Electrolytes: Taken from blood vessels and secreted by secretory cells. Types of Secretory Glands in the GI Tract: 1. Single-Cell Secretory Glands: Example: Goblet cells. 2. Pits (Epithelium Invaginations): Crypts of Lieberkühn: Found in the small intestine. Tubular Glands: Found in the stomach. 3. Complex Glands: Example: Mucus glands in the lower esophagus. 4. Organs (Located Outside the Tubular GI Structure): 1.Salivary glands 2.Pancreas. 3.Liver Regulation of glandular secretion Role of the ENS: The presence of food in certain segments usually stimulates glandular secretions. This appears as a response to mechanical or chemical stimulation, which induces activation of secretory reflexes that are responsible for the increased secretions by gland. Role of the Autonomic Nervous System: 1. Parasympathetic Stimulation: Increases the rate of glandular secretions. 2. Sympathetic Stimulation: Causes a moderate increase in glandular secretion by enhancing vesicular transport (increasing the secretion of organic materials). Reduces the secretion of water and electrolytes by decreasing blood flow through its effect on vessels. Hormonal Regulation: Certain hormones are secreted in response to the presence of food in digestive organs. These hormones stimulate glands to increase secretions. Salivary Glands Secretion: Secretion: Defined as the net movement of water, electrolytes, and proteins (such as the starch- splitting enzyme amylase and glycoproteins) into the lumen of the salivary duct. Role of Acinar Cells in Secretion: Secretion of Water and Electrolytes: Water and electrolytes originate from extracellular fluid. Acinar cells are surrounded by a capillary plexus, which plays a critical role in glandular secretion. Proposed Steps of Secretion: 1. Active Transport of Cl⁻: At the basal membrane, active transport of Cl⁻ increases the membrane’s negative potential. 2. Attraction of Na⁺: The increased negative potential attracts Na⁺ ions.  3. Osmotic Pressure Increase: Elevated osmotic pressure inside the cell draws water into the cell, increasing hydrostatic pressure within the acinar cells. 4. Rupture at the Apical Membrane: The increased hydrostatic pressure causes minute ruptures at the apical membrane of the secretory cells. This results in the flushing of water, electrolytes, and organic materials into the lumen. Synthesis and secretion of protein components: 1. Synthesis of Proteins: Proteins such as ptyalin, lingual lipase, and mucin are synthesized in the endoplasmic reticulum (ER) of acinar cells. These proteins are transported via vesicular transport toward the apical (luminal) membrane, where they are secreted by exocytosis. 2. Energy Supply: Secretory cells are rich in ER and mitochondria. Mitochondria provide the energy needed for transport of nutrients essential for synthesisand the process of protein synthesis itself. 3. Primary Secretion by Acinar Cells: Acinar cells secrete a primary solution containing ptyalin and mucin, along with electrolytes. The water and electrolyte concentration in the primary secretion is comparable to that of extracellular fluid. Role of Duct Cells in Saliva Composition As saliva flows through the ducts, its ionic composition is modified through two major processes: 1. Na⁺ Reabsorption and K⁺ Secretion: Mediated by the Na⁺/K⁺ pump, which creates a negative trans-cellular potential, inducing reabsorption of Cl⁻ ions. 2. HCO₃⁻ Secretion into the Duct: Occurs through: Exchange of HCO₃⁻ for Cl⁻ ions. Active transport of HCO₃⁻. Final Saliva Composition The final saliva is hypotonic because of reabsorption of Na⁺ and Cl⁻ exceeds secretion of K⁺ and HCO₃⁻. Net Ionic Changes in Final Saliva: Na⁺ and Cl⁻ Concentrations: Reduced to 1/10 of their plasma concentrations. K⁺ Concentration: Increased by 7-fold. HCO₃⁻ Concentration: Increased by 2–3-fold. The amount of secretion by saliva is about 1500ml/day. The rate of secretion is less than 0.025 (during sleep) to about 0.5ml/min (during the basal conditions). The spontaneous secretion of saliva is maintained by a constant low level of parasympathetic stimulation. Salivary Glands Contribution and Secretion Types: 1. Parotid Glands: Contribute ~25% of saliva. Secrete serous (watery) saliva. 2. Submandibular (Submaxillary) Glands: Contribute ~70% of saliva. Secrete mixed saliva (serous and mucus). 3. Sublingual Glands: Contribute ~5% of saliva. Secrete mucus saliva. pH of Saliva: Resting Secretion: ~7.0. Active Secretion: Approaches ~8.0. Changes in Saliva During Stimulation 1. Maximal Stimulation: Primary saliva production can increase up to 20-fold due to heightened activity of acinar cells. Increased flow rate through ducts reduces the reabsorptive and secretory activity of duct cells.  2. Impact on Secondary (Final) Saliva Composition: Higher Concentrations: Na⁺ and Cl⁻. Lower Concentrations: K⁺ compared to lower flow rates. Control of salivary Secretion Aldosterone: Stimulation of Salivation 1. Unconditioned Salivary Reflex: Triggered by chemo-receptors or pressure-receptors in the oral cavity (e.g., during eating or dental procedures). Receptors send signals via afferent fibers to salivary centers in the medulla, which respond with stimulatory signals via efferent fibers through autonomic nerves to increase salivation. 2. Conditioned Salivary Reflex: Triggered by stimuli such as thinking about, seeing, smelling, or hearing about pleasant food (e.g., “mouth watering”). This is a learned response based on past experiences. 3. Nervous Regulation: Both sympathetic and parasympathetic systems stimulate salivation, but via different mechanisms. High Sympathetic Activity: May reduce salivation due to its vasoconstrictive effects on blood supply. Functions of Saliva 1. Initiation of Carbohydrate Digestion: Salivary amylase breaks down polysaccharides into maltose (a disaccharide composed of two glucose units). 2. Facilitation of Swallowing: Moistens Food: Ensures food particles are easily gathered and swallowed. Lubrication:Mucus protects the mucosa during swallowing.Reduces friction, preventing physical damage to the mucosa.  3. Antibacterial Actions: Lysozyme: Destroys certain bacteria. Continuous Saliva Flow: Rinses away food residues, epithelial cells, and foreign particles, aiding in oral hygiene. Immunoglobulin A (IgA): Contributes to bacterial destruction. 4. Taste Facilitation: Acts as a solvent for molecules that stimulate taste buds. 5. Speech Aid: Enables smooth movements of lips and tongue, aiding in articulation. 6. Neutralization of Acids: Bicarbonate neutralizes acidic food and bacterial acids, helping to prevent dental caries. Esophageal Secretion 1. Simple Mucus Glands: Secrete mucoid substances that aid in lubrication and protect the esophageal mucosa from damage during swallowing. 2. Compound Mucus Glands (Near the Esophago-Gastric Junction): Secrete alkaline mucus, which protects the esophageal wall from gastric reflux by neutralizing acidic contents Gastric Secretion Mucus-Secreting Cells: Line the entire surface of the stomach. Functions of Viscid Mucus: 1. Lubrication: Protects against mechanical injury. 2. Protection from Proteolytic Enzymes: Prevents enzymes from digesting the stomach mucosa. 3. Neutralizing HCl: Alkaline pH of mucus shields the mucosa from chemical injury caused by HCl. Tubular Glands: Oxyntic (Gastric) Glands: Secrete HCl, intrinsic factor, and mucus. Contain three types of cells: Mucus Neck Cells: Secrete mucus and some pepsinogen. Peptic (Chief) Cells: Secrete large amounts of pepsinogen. Parietal (Oxyntic) Cells: Secrete HCl and intrinsic factor. ———————————————————————————————— Mechanism of HCl Secretion: Proposed mechanism for acid secretion by parietal cells: 1. Cl⁻ Active Transport: Cl⁻ is actively transported into the canaliculus, creating a negative potential that drives passive diffusion of K⁺ and Na⁺ (primarily K⁺). 2. H⁺ Formation: The H+ is taken from dissociated water during the reaction catalyzed by carbonic anhydrase. In the presence of CO2 and the activity of carbonic anhydrase, HCO3- and H+ are formed. Catalyzed by carbonic anhydrase: H₂O + CO₂ → H₂CO₃ → HCO₃⁻ + H⁺ HCO₃⁻ is transported to the interstitial fluid in exchange for Cl⁻. 3. H⁺ Active Secretion: H⁺ is pumped into the canaliculus via the H⁺/K⁺ pump. Na⁺ is absorbed via active transport. 4. Water Movement: Water enters the canaliculus by osmosis. Net Reaction: H₂O + CO₂ + NaCl → NaHCO₃ (blood) + HCl (lumen) H⁺ Concentration: [H⁺] in the canaliculus is ~3 million times higher than in blood, significantly lowering pH during secretion. ATP is required for H⁺ pump activity. At Rest vs. Stimulation: Resting: NaCl secretion. High Stimulation: HCl secretion. Potential difference drops from ~–70 mV (rest) to ~–30 mV (stimulation). ———————————————————————————————— Importance of HCl: HCl does not usually digest any thing, but it is important because it: Activates pepsinogen into pepsin. Decomposes connective tissue. Kills microorganisms ingested with food. Pepsinogen Secretion Secreted by chief (peptic) and mucus cells in an inactive form. Converted into pepsin in an acidic environment (pH 1.8–3.5). Importance of Pepsin: Breaks long polypeptides into smaller peptides. Intrinsic Factor Secretion Secreted by parietal (oxyntic) cells. Essential for vitamin B12 absorption. Lack of intrinsic factor (e.g., gastric mucosal atrophy) leads to pernicious anemia, characterized by impaired RBC maturation. ———————————————————————————————— Pyloric Glands Contain: Mucus Cells: Similar to mucus neck cells of gastric glands. G Cells: Secrete Gastrin. Gastrin: Released into the blood. Acts on the stomach to: 1.Increase HCl and pepsinogen secretion. 2.Maintain gastric mucosal growth (trophic effect). Control of Gastric secretions: Regulation of HCl secretion: 1. Neural: - Enteric Nervous System: can control by direct stimulation of parietal cells and peptic cells. The effect is mediated by Ach.- Parasympathetic: vagal activation during cephalic and gastric phases (via long arc reflex) activate: ○ enteric excitatory neurons to release Ach. ○ enteric neurons that innervate enterochromaffin-like cells in the stomach to secrete Histamine. ○ enteric neurons that secrete GRP (gastrin releasing peptide) that acts on G cells to causesecretion of Gastrin. 2. Hormonal: Gastrin: secreted from G cells into the blood and acts on parietal cells to increase HCl secretion. The release is stimulated by gastric distention, presence of proteins in chyme and vagal stimulation. This hormone acts on a receptor at parietal cells known as CCK-B receptor to increase the intracellular Ca++ and activation of oxyntic cells to secrete HCl. This receptor can also be activated to a lesser extent by CCK (cholecystokinin). 3. Paracrine:- Histamine:secreted by enterochromaffin-like cells in response to vagal stimulation and local Inflammation. Diffuses in the extracellular space and activates parietal cells via H2 receptor by increasing c-AMP as a second messenger. Net effect = increase HCl secretion. Note: Some antihistaminic drugs that block H2 receptors such as Cimetidine.reduces acid secretions - Somatostatin (SS): released from paracrine cells in the mucosa and acts on SS receptors of parietal cells to decrease cAMP. Net effect → decrease HCl secretion. Note: Excess of acids causes feed back Regulation of pepsinogen secretion: inhibition of gastric secretions by 2 ways: - Reduction of gastrin release Ach, Gastrin, HCl: - Initiation of inhibitory reflexes.As a result, this HCl acts indirectly by initiating enteric.will maintain pH NOT to fall below 3 reflexes that causes an increase in pepsinogen secretion by peptic cell. 3 phases of control of gastric secretions: - Cephalic phase: by thinking about, smelling, tasting, chewing or swallowing. In this phase vagal stimulation is involved. These acting before food reaching the stomach to stimulate parietal cells and G cells. - Gastric phase: Acts when food reaches the stomach to cause maximal stimulation of gastric secretions. - Distension and the presence of proteins in food stimulates local reflexes and long reflexes which results in increased gastric secretion. - Caffeine and alcohol also stimulate acid secretions even no food is present in the stomach. - Intestinal phase: - Excitatory: Distension of the upper portion of the duodenum can slightly stimulate gastric secretions. This effect is probably by the release of gastrin. Inhibitory: the presence of chyme in intestine usually inhibits gastric secretions. The presence of food and acids in duodenum initiates neural reflexes (enterogastric reflex) and causes the release of hormones (GIP, CCK, secretin, enterogastrone)..These hormones inhibit acid secretions. INTESTINAL SECRETION: (1500ml/day) - Cells of mucosal epithelium secrete mucus, water and electrolytes. - Tubular glands in submucosa of duodenum (duodenal glands). These invaginations of epithelium known as crypts of Leiberkuhn which empty into the lumen of duodenum. These glands secrete serous secretionRegulation: - Local neural mechanisms that activates secretions is mediated by Ach and VIP (vasoactive intestinal peptide) neurons. - Secretin: increases duodenal secretion. This is an important factor to neutralize the acid delivered into the duodenum from the stomach. COLONIC SECRETION: - Mostly mucus secretion. - Small amount of serous secretions which is rich in K+ and”HCO3-. _________________________________________ PANCREATIC SECRETION: (1-2L/day) Functional anatomy: - Endocrine portion: Islets of Langherhans secrete insulin, glucagon, somatostatin and pancreatic polypeptiderelease into the blood. - Exocrine portion: Enzymes: secreted from acinar cells and water and bicarbonate are secreted by duct cells. These are secreted into the duodenum via 10pancreatic duct and common bile duct. Which empty at ampula of Vater through sphincter of Oddi.The net pancreatic secretion is high in enzymes and is hypotonic and alkaline. Secretion of Pancreatic enzymes: Pancreatic enzymes are synthesized by acinar cells and stored in zymogen granules. The proteolytic enzymes are stored as inactive enzymes and become activated in the duodenum. - Protelytic enzymes: - Trypsinogen (trypsin (ogen)): activated by enterokinase from the duodenum (become trypsin). Trypsin acts as an endopeptidase. As long as it is in pancreas, Trypsinogen remains inactive by trypsin inhibitor. - Chymotrypsin(ogen): activated by trypsin and acts as an endopeptodase. - (Pro) carboxypeptidase: activated by trypsin and acts as exopeptidase. - Pancreatic amylase: secreted in an active form to convert polysaccharide in disaccharide. - Lipolytic enzymes: - Lipase: esterase that splits triglycerides into monoglyceride and free fatty acids. Their activity requires an oil/water interface, bile salts (secreted by liver) and other co-lipase secreted by the pancreas. - Phospholipase. - Cholesterol ester hydroxylase. Note: Pancreatic insufficiency (characterized by decreased enzyme secretion) is manifested as steatorrhea (yellowish stool due to the presence of undigested fat) Secretion of water and bicarbonate: Water and bicarbonate are secreted by duct cells. The pancreatic secretion has an alkaline pH to neutralize the acids when emptied into the duodenum from the stomach and provide an optimal pH for enzymatic function. Mechanism of secretion: An enzyme (CA) is involved in catalyzing the following reaction: Carbonic Anhydrase (CA) H2O + CO2 → H2CO3  H+ + HCO3- ○ HCO3- is transported at the luminal border by secondary active transport in exchange with Cl-. ○ H+ is transported by a secondary active transport in exchange with Na+ at blood border. ○ Na+ is transported from the cell by an active transport. ○ Water osmosis. Note: The final composition varies with the rate of secretion. * At high rates: HCO3- is high and Cl- is low..* At low rates : HCO3- is low and Cl- is high Regulation of pancreatic secretion: Neural control: - Parasympathetic: Vagal stimulation is excitatory via stimulation of neurons in the enteric nervous system innervating the acinar cells. These causes local release of Ach, VIP, and GRP (Gastrin releasing peptide). - Sympathetic: indirect inhibition via vasoconstriction of blood supply to the pancreas Hormonal regulation - Secretin: major stimulant of water and HCO3-secretion. This secreted into the blood by duodenal mucosa to acid stimulation → acts on duct cells to activate HCO3- and water secretion in response to the presence of acid in the duodenum. - CCK (Cholecystokinin): the major stimulant of enzyme secretion. Released by duodenal mucosal cells into the blood in response to fat products and proteins in chyme. Acts directly through CCK-A receptors on acinar cells to increase enzymatic secretion. CCK also acts indirectly through vagovagal reflex to stimulate enzyme secretions. Other effects of CCK is contraction of the gallbladder and relaxation of sphincter of Oddi by both ways directly and indirectly. - Pancreatic polypeptide: inhibits the release of enzymes by its inhibitory effects: - On the release of Ach from enteric nervous system. - On vagal output of the CNS. 3 phases of control of pancreatic secretions: Cephalic phase: sight, smell, taste or hearing. Reflex is mediated by vagus. Gastric phase: Distension. Effect is mediated by vagus. Intestinal phase: local changes are caused by: Aminoacids (aa), Fatty acid, Distension. The effect of local changes is Mediated by CCK, secretin, enteropancreatic reflexes and other hormones. LIVER SECRETIONS: Largest and the most important metabolic organ. It has importance in the digestive mechanisms by the formation and secretion of bile salts. This organ also performs the following functions: 1. metabolic processes: Process all nutrients after their absorption. 2. Detoxification of body wastes, hormones, drugs, and other foreign bodies. 3. Synthesis of plasma proteins, including clotting factors (their synthesis requires vit. K), hormone transporters. 4. Storage organ of glycogen, iron (ferritin), copper, and vitamins. 5. Removal of bacteria and foreign materials by reticuloendothelial cells (Kupffer cells). 6. Excretion of cholesterol and bilirubin. Here’s a simplified explanation and arrangement of the functional structure of the liver: Functional Unit: Hepatic Lobule The liver is made up of many hepatic lobules, which are the basic functional.units.Each lobule has a hexagonal shape and surrounds a central vein Components of the Lobule: 1. At the edges of the hexagon (triad region), you’ll find : ○ Branch of the hepatic artery: Brings oxygen-rich blood. ○ Branch of the portal vein: Brings ”nutrient-rich blood from the digestive system. ○ Bile duct: Carries bile away from the liver. 2. Inside the Lobule: Hepatocytes (liver cells): Arranged In layers, two cells thick. Sinusoids: Small channels where blood from the hepatic artery and portal vein flows toward the central vein. Central vein: Collects blood and carries it out of the lobule. Special Structure: Bile Canaliculi: Tiny channels between hepatocytes that collect bile produced by these cells. Space of Disse: The space between hepatocytes and the sinusoids where lymph circulates. Blood and Bile Flow: Blood Flow: 1. Blood enters from the hepatic artery and portal vein at the edges of the lobule. 2. It flows through the sinusoids, passing between of hepatocytes. 3. Blood then drains into the central vein, which eventually leads to the hepatic vein and back to the heart. Bile Flow: 1. Hepatocytes produce bile, which enters the bile canaliculi. 2. Bile flows toward the bile ducts at the edges of the lobule. 3. From there, it travels through the common bile duct to the duodenum (first part of the small intestine). This arrangement ensures efficient processing of nutrients, detoxification, and bile production. Excretion of bilirubin with bile: Bilirubin results from the catabolism of hemoglobin → Heme + Globin Heme ring decomposed into iron + biliverdin Note: Jaundice (yellow discoloration of Biliverdin is transformed into bilirubin and the skin) is caused by the presence of secreted in bile as conjugated with (glucoronide, high concentration of bilirubin in the sulfate, other substances). extracellular space. In intestine, bilirubin is transformed (by bacterial action) into urobilinogen. This will be reabsorbed and secreted in urine as (urobilin) or secreted with feces as stercobilin. Bile synthesis and secretion: - The digestion and absorption of lipids present a special problem. The environment in thelumen of intestine is an aqueous environment in which lipids are not soluble. To make lipids soluble, bile is added to the small intestine at the level of duodenum. Bile acts as detergent to emulsify lipids and make them soluble. - Bile is composed of bile salts, water & electrolytes, cholesterol, phospholipids and wastes intended for excretion, (bilirubin). - Bile salts are synthesized by the liver, concentrated in the gallbladder and modified in the lumen. The liver produces substances called bile acids from cholesterol. Specifically, it makes two primary bile acids: cholic acid and chenodeoxycholic acid. However, these acids are usually secreted in a different form called bile salts, which are created when bile acids combine with certain amino acids (glycine or taurin) ○ Bile is a fluid that helps with digestion, and its initial form contains water,(isotonic) sodium (Na⁺), potassium (K⁺), and chloride (Cl⁻). As this secretion moves through ducts in the liver, some cells in the ducts change it by swapping bicarbonate (HCO₃⁻) for chloride (Cl⁻). The hormone secretin increases the.release of bicarbonate ○When you are not eating (between meals) , bile is stored in the gallbladder. Here, water and electrolytes are removed by epithelium of the gallbladder , making the bile 5-20 times more concentrated. ○ During a meal, the gallbladder contracts and the sphincter of Oddi relaxes, allowing bile to flow into the intestine. This is triggered by nerves and a hormone called CCK (cholecystokinin), which is released when fats and proteins reach the duodenum (the first part of the small intestine). ○ In the intestine, bile helps digest fats. After that, bile salts are reabsorbed in the last part of the small intestine (the terminal ileum). They removed from the blood by liver re- secreted in the bile. This cycle of bile salts being secreted, reabsorbed, and reused is called enterohepatic normal meal bile salt is circulation during recirculated twice ○ About 20% of bile salts are lost daily in feces, and the liver makes new bile acids to replace them(By de nova synthesis of bile acids by the hepatocytes) In the intestine, bacteria change the primary bile acids into secondary bile acids: Cholic acid becomes deoxycholic acid. Chenodeoxycholic acid becomes lithocholic acid. In summary, the liver makes bile acids, stores bile in the gallbladder, and bile helps digest fats during meals. The body efficiently reuses bile salts, but a small amount is lost each day and replaced by the liver. ‫تمت كتابة هذا الشيت صدقة جارية عن روح والدة زميلنا عمرو رائد من دفعة تيجان‬ ‫دعواتكم لها بالرحمة والمغفرة‬ Thank you , good luck ☺