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❖ Digestive System VERSION 4 Dua’a Alodat Mohammed Rami Digestive System Faris Katbi ❖ It’s the place where the food will be digested ❖ Organization of the Digestive System: Gastrointestin...

❖ Digestive System VERSION 4 Dua’a Alodat Mohammed Rami Digestive System Faris Katbi ❖ It’s the place where the food will be digested ❖ Organization of the Digestive System: Gastrointestinal tract (GIT) Accessory organs 1. Mouth 1. Salivary Glands 2. Oropharynx 2. Liver 3. Esophagus 3. Gallbladder 4. Stomach 4. Pancreas 5. Small intestine (most of the Reabsorption occur here) 6. Large intestines (10% of the Reabsorption Occur here) ❖ Functions of the Digestive Tract: 1. Ingestion: Occurs when solid food and liquid enter the oral cavity. 2. Mechanical digestion: Involves crushing of food in the oral cavity and mixing in the stomach. 3. Chemical digestion: Chemical and enzymatic breakdown “ hydrolysis “ of food into small organic molecules that can be absorbed by the digestive epithelium. 4. Secretion: Enzymes and digestive fluids secreted by the digestive tract and its accessory organs facilitate chemical digestion, it’s done by neural and Hormonal Control. 5. Absorption: Passage of the nutrients of chemical digestion from the digestive tract into blood or lymph for distribution to tissue cells, most of it done in Small intestine and 10% of it done in large intestine (Colon) 6. Elimination: Undigested material will be released through the rectum and anus by defecation. ❖ Structure of the GIT: 1. Mucosa (inner lining) ▪ The innermost epithelial membrane that lines GIT. ▪ Secretes mucus that lubricates and protects GIT. 2. Submucosa ▪ Layer of dense irregular connective tissue. ▪ Contains blood vessels and lymphatic vessels ▪ Contains exocrine glands in some regions. 3. Muscularis propria (externa) ▪ Two layers of smooth muscle (inner circular layer; outer longitudinal layer). 4. Serosa ▪ Outermost layer of loose connective tissue. ▪ Secrets fluid that lubricates the outside of the GI tract. ❖ Musculature of the GIT 1. Longitudinal muscle layer ▪ Contraction shortens the segment of the intestine and expands the lumen. ▪ Innervated by enteric nervous system (ENS). 2. Circular muscle layer ▪ Thicker and more powerful than longitudinal. ▪ Contraction reduces the diameter of the lumen and increases its length. ▪ Innervated by ENS 3. Oblique muscle layer (ONLY STOMACH) ▪ they help to bring food together to the digestive secretion inside the stomach 1 ❖ Characteristics of GI Smooth Muscle ▪ Each muscle layer functions as a syncytium. (Contract as one Unit) ▪ There are large numbers of actin filaments attached to (dense bodies). ▪ Some of the dense bodies of adjacent cells are bonded together by intracellular protein bridges (gap junction). ▪ There is continuous slow intrinsic electrical activity. ▪ Most GI contractions occur rhythmically. ❖ Electrical Activity of GI Smooth Muscle Slow waves “ Basic electrical rhythm “ + “ Prominent type “ ▪ Are not action potentials (AP). ▪ Caused by interaction between smooth muscle cells & interstitial cells of Cajal ▪ Occur at different frequency: 1. Stomach (3/min) 2. Duodenum, (12-18/min) 3. Ileum & colon (6-10/min) Spike potential ▪ Are true AP. ▪ Occur when resting membrane potential become more positive than -40 mv. ▪ The higher the slow wave potential the greater the frequency. ▪ Ca2+ - Na+ channels are responsible for Ap. ▪ Cause muscle contraction. ❖ Patterns of Smooth Muscle Contraction Phasic contractions: Periodic contractions followed by relaxation (as in small intestine and esophagus). Tonic contractions (VALVES) ▪ Maintained contraction without relaxation. ▪ Not associated with slow wave ▪ Caused by 1. Continuous repetitive spike potential. 2. Hormonal effects 3. Continuous entry of Calcium. ❖ Muscular Movement of The GIT. 1. Mixing ▪ Mixing motion in the oral cavity and stomach that allows the GI tract to break down food into smaller particles. 2. Peristalsis ▪ Wavelike movement that occurs from the oropharynx to the rectum to push food particles toward the anus. 3. Segmentation ▪ Independent contraction and relaxation of regions of the small intestine, allowing the small intestine to digestive and absorb more efficiently. 2 ❖ Regulation of GI Activities A. Autonomic nervous system (ANS) 1. Sympathetic nerves inhibit GI tract activities. 2. Parasympathetic nerves stimulate GI tract activities. 3. Enteric nervous system (ENS) ▪ Neurons are grouped in thousands of ganglia. ▪ Sympathetic and parasympathetic fibers connect ENS to CNS 1. Myenteric plexus: ▪ Organized in a network around gut. ▪ Controls movements and contraction. 2. Submucosal plexus: ▪ Localized in small and large intestine (conveying information to the brain) ▪ Controls secretions. B. Hormonal control ▪ Hormones from GI tract and endocrine gland help regulate GI tract activities. ▪ Enteroendocrine cells release peptide hormones and biogenic amines (serotonin, histamine, gastrin). ▪ intestinal Mucosa Are the largest Endocrine Cell in our Body. C. Local factors ▪ Changes in pH of contents in lumen. ▪ Presence of chemicals. The Mouth ▪ Food is broken down by mechanical digestion (using mastication). ▪ Chemical digestion through amylase enzyme in saliva that breaks down polysaccharide into disaccharides. ▪ The tongue manipulates the food during mastication and detect taste sensations. ▪ Food particles are mixed with saliva during mastication, resulting in a moist lump called bolus. Salivary Glands ▪ Secret saliva, Under neural control. ▪ Saliva consists of 99.5% water and 0.5% is dissolved substances (HCO3 -, electrolytes and amylase enzyme). ▪ Functions of saliva: ▪ Three pairs of salivary glands: 1. Moisten food and the mouth during mastication 1. Sublingual gland. 2. Clean the teeth and inhibit bacterial growth. 2. Parotid gland. 3. Digest a small amount of starch via amylase enzyme. 3. Submandibular gland. ➔ Polysaccharide into maltose Esophagus Actively moves food from the throat to the stomach. Control of movement: “ Primary peristaltic waves “ 1. Upper esophageal sphincter: “pharyngoesophageal sphincter “ ▪ Circular muscle tissue. ▪ Prevents air from entering the esophagus. 2. Lower esophageal sphincter (cardiac sphincter): ▪ At the inferior end of the esophagus. ▪ Normally contracted (prevents backflow of stomach contents). 3 Stomach Muscular, expandable, J-shaped organ. Highly variable shape depending on contents: a. Empty: muscular tube with constricted lumen. b. Full: can expand to contain 1–1.5 L of material (chyme) Viscous and highly acidic mixture formed from combination of food, saliva and gastric secretions. Stomach Regions: 1. Fundus: Superior to the junction between the stomach and esophagus. 2. Cardia: Junction between the lower esophagus and the stomach. Secretes mucus to protect esophagus from stomach acid/enzymes. 3. Body: Largest region + Between the fundus and pylorus + function as a mixing bowl 4. Antrum: Last part of the stomach before the pylorus. 5. Pylorus ▪ Sharp curve of “J” of the stomach. ▪ Frequently changes shape with mixing movements. ▪ Contain the pyloric sphincter (Which is the output Zone from the stomach to the duodenum). Functions of the Stomach: 1. Temporary storage of ingested food, Most of this occurs in the body of the stomach. 2. Mechanical digestion of ingested food, The mixing movements of the stomach produces chyme. Most of this mixing occurs in the antrum. 3. Chemical digestion of food through the action of acid and enzymes (HCl to begin protein digestion). 4. Production of intrinsic factor. Gastric Glands 1. Glands in the fundus and body “ Oxyntic mucosa “ ▪ Secrete most of acid and enzymes enabling gastric digestion. ▪ Dominated by parietal cells and chief cells. ▪ Secrete 1.5 L of gastric juice each day. 2. Glands in the pylorus ▪ Secrete mucus and hormones that coordinate and control digestive activity. ▪ Shallow depressions opening onto the gastric surface (Gastric pits). ▪ Each pit communicates with several gastric glands. Gastric Gland Cells Two liters of gastric juice are secreted per day. Secretion is isotonic, pH 2-3 (in stomach lumen).  G cells (enteroendocrine cells): Produce hormones ➔ Gastrin.  Parietal cells (oxyntic) secrete:  D cells ➔ secrete Somatostatin. a) Intrinsic factor:  Enterochromaffin like cells ➔ Secrete Histamine. ▪ Glycoprotein  Mucous neck cells and surface epithelial cells ➔ Mucus. ▪ Aids in VB12 absorption. ▪ Protects gastric epithelium b) Hydrochloric acid (HCl): ▪ Adheres to gastric surface. ▪ Activates pepsinogen. ▪ Prevents H+ and pepsin eroding mucosa. ▪ Keeps stomach at pH 1.5–2.0.  Chief (peptic) cells ➔ secrete: ▪ Kill micro-organisms. a) Pepsinogen: Activated by HCl to become pepsin. ▪ Breaks down connective tissue in food. b) Rennin and gastric lipase: important for the digestion of milk. ▪ Denatures protein. 4 ✓ Pepsinogen ▪ Is secreted as inactive enzyme. ▪ Activated by HCl forming pepsin. ✓ Pepsin ▪ Activates more pepsinogen (autocatalytic process). ▪ Works in acidic media (pH 1-2). ▪ Initiates protein digestion. ▪ If secreted in his Active Form, he will digest the wall of stomach. ✓ HCl Production ▪ Parietal cells do not create HCl in their cytoplasm (destroy the cell). ▪ STEPS: 1. H+ and Cl– are transported and secreted separately. 2. H+ is generated as carbonic anhydrase converts CO2 and H2O to carbonic acid. 3. Carbonic acid dissociates into bicarbonate ions and hydrogen ions. (CO2+ H2O →H2CO3→HCO3– + H+) 4. Bicarbonate ejected into the interstitial fluid in exchange for a chloride ion. 5. From the interstitial fluid, bicarbonate enters the blood stream. → If gastric glands very active, amount of bicarbonate released is enough to increase the pH of the blood. → Sudden influx of bicarbonate ions is called the alkaline tide. 6. Chloride ions diffuse across cell and exit into the gastric gland lumen. 7. Hydrogen ions are also actively transported into the gastric gland lumen. ❖ Regulatory Pathways Acetylcholine (Ach): ▪ Released from intrinsic nerve plexuses. ▪ Stimulates G cells and Enterochromaffin like cells. Gastrin: ▪ Secreted into blood from G cells in response to: Protein products in the stomach & Ach. ▪ Stimulates both parietal and chief cells. ▪ Stimulates histamine release from ECL. ▪ histamine stimulates HCL release from parietal cells. Inhibitors of HCl Secretion: 1. Somatostatin ▪ Released by gastric D cells ▪ In response to high acidity is the central inhibitory mechanism of acid production. ▪ Directly inhibits parietal cell acid production. ▪ Inhibits ECL histamine release. ▪ Inhibits release of gastrin from G cells. 2. Secretin from duodenal cells plays the main role in inhibiting acid secretion after the entry of fat and acid into duodenum. 3. Cholecystokinin (CCK) also inhibits acid secretion. 5 ❖ Stomach Activity ▪ As food empties from stomach into intestine, gastric secretion gradually decreases. ▪ Gastric mucosal barrier protects stomach lining from gastric secretions. ▪ Carbohydrate digestion continues in body of the stomach. ▪ Proteins digestion begins in the antrum. ▪ The stomach absorbs alcohol and aspirin, but does not absorb food. ❖ Phases of Gastric Secretion Cephalic phase ▪ Before food enters stomach. ▪ Stimuli from the head increase the secretion of HCL and pepsinogen. ▪ Impulses carried by vagus nerve: → Direct stimulation of parietal cells. → Indirect stimulation of G cells. Gastric phase ▪ Food in stomach. ▪ Stimuli acting in stomach itself. ▪ Stimulate chemoreceptors in stomach, resulting in stimulation of: → Intrinsic nerves plexus (enteric) → Extrinsic nerves (vagus). Intestinal phase ▪ After food enters small intestine. ▪ Inhibitory effect of secretin and cholecystokinin. ▪ decrease the flow of gastric juices. ❖ Gastric Filling ▪ Stomach accommodates a 20-fold increase in volume with little changes in tension in its wall. ▪ The reflex relaxation of the stomach is called receptive relaxation. ▪ Receptive relaxation is mediated by vagus nerve. ❖ Gastric Storage and Mixing ▪ Food is stored in stomach body. ▪ Basic electrical rhythm (BER) occurs continuously and initiate contraction (peristaltic movement). ▪ Peristaltic movement spreads over fundus and body to the antrum. ▪ Peristaltic waves (contraction) in the antrum are strong to mix food. ▪ Peristaltic waves are weak in the fundus and body of the stomach. ▪ Each time strong antral contraction occurs, it pushes food forward toward the pyloric sphincter which is closed so food returns back. ▪ Such movements will mix the food with digestive food and converting food into semi fluid called chyme ❖ Gastric Emptying ▪ Strong peristaltic contractions force chyme to pass through pyloric sphincter into duodenum. ▪ The amount of chyme passing depends on: ▪ The strength of contractions which are controlled by signals from stomach itself and the duodenum 6 ❖ Pancreas Soft tubular gland connected to duodenum by two ducts: Exocrine (secretory), Endocrine (hormonal). Consists of head, body and tail. Pancreatic duct: Accessory pancreatic duct (Santorini duct): ▪ Delivers exocrine secretions to duodenum. ▪ Branches from pancreatic duct. ▪ Pancreatic juice (1000 ml /day). ▪ Empties separately into duodenum. Pancreatic tissue: Dominated by pancreatic acini: Pancreatic islets: ▪ Produce digestive enzymes and buffers. ▪ Contain endocrine cells. ▪ Contain pancreatic acinar cells. ▪ Secrete pancreatic enzyme. Exocrine and Endocrine Cells: Exocrine cells: Endocrine cells (islets of Langerhans): ▪ Secrete pancreatic juice consisting of: ▪ Secrete hormones (insulin and glucagon) to blood. a) Digestive enzymes (secreted by acinar cells). b) Aqueous alkaline fluid (sodium bicarbonate secreted by duct cells). ▪ Exocrine secretion is regulated by (from small intestine): a) Secretin stimulates secretion of sodium bicarbonate from pancreas. b) CCK stimulates secretion of pancreatic digestive enzymes. Major Pancreatic Enzymes Pancreatic alpha-amylase: Nucleases: ▪ Digest carbohydrate. ▪ Ribonuclease: digests RNA to nucleotides. ▪ Identical to salivary amylase. ▪ Deoxyribonuclease: digests DNA to nucleotides. Proteolytic enzymes: Pancreatic lipase: ▪ Break proteins apart into mixture of ▪ Only enzyme can digest fat: ▪ dipeptides, tripeptides, and amino acids. ▪ Triglycerides ➔ monoglycerides + free fatty acids ▪ Secreted as inactive proenzymes. ▪ Releases products that can be easily absorbed. ▪ Activated in the duodenum autocatalysis ▪ Active forms include trypsin, chymotrypsin, carboxypeptidase, elastase. ▪ Enterokinase is produced by duodenal epithelial cells. ▪ Converts trypsinogen into active proteolytic enzyme (trypsin). ▪ Once trypsin is formed, it activates chymotrypsinogen and procarboxypeptidase. Regulation of Pancreatic Secretion 1) Neural factors: Parasympathetic nervous system stimulate pancreatic secretion. 2) Hormonal factors: a) Secretin: ▪ Stimulated by acidity of chyme. ▪ Increase alkaline watery secretion from pancreatic ducts. b) Cholecystokinin (CCK): ▪ Stimulated by presence of fat and protein in the chyme. ▪ Excites acinar cells to produce digestive enzymes. 7 ❖ Liver Liver is organized into functional units (lobules). Hexagonal arrangements of tissue surrounding a central vein. Liver cells Liver sinusoids ▪ Liver lobules contain hepatocytes (liver cells). ▪ Delicate blood vessels. ▪ Form series of irregular plates. ▪ Lack a basement membrane. ▪ Plates of hepatocytes are separated by liver sinusoids ▪ Resemble large fenestrated capillaries. ▪ Kupffer cells: macrophages engulf pathogens and damaged blood cells. Hepatic Portal System ▪ is the system of veins that transports blood from the digestive tract to the liver. ▪ It consists of the hepatic portal vein and other veins, that drain into the hepatic portal vein. ▪ The blood pumped from the heart to all body organs, reach GIT. ▪ Some part of GIT absorbed food and nutrients. ▪ These nutrients should be send to liver to processing via hepatic portal vein. ▪ In the liver blood flows from periphery to center, then back to heart. Liver Functions 1) Production of bile (flows from center to periphery). 2) Metabolic processing of nutrients. 3) Detoxification of blood. 4) Synthesis of most plasma proteins and clotting factors. 5) Storage of substances such as glycogen and fats. 6) Deamination of amino acids ➔ removing nitrogen, producing ammonia and eventually urea (to kidneys). 7) Removal of bacteria and old red blood cells. 8) Excretion of cholesterol and bilirubin. ❖ Gallbladder ▪ Bile: Bitter-tasting, dark green to yellowish brown fluid, produced by liver (800 – 1000 ml/day). ▪ Stored in gallbladder for release on demand into small intestine (duodenum). ▪ Aids in process of digestion of lipids in small intestine (acts as an Emulsifier). Bile Constituents 1) Water (85%). 2) Bile salts (derivatives of cholesterol, (10%)). 3) Mucus and pigments (3%). 4) Fats (1%). 5) Inorganic salts (0.7%). 6) Cholesterol (0.3%). 7) Lecithin (yellow phospholipid essential for metabolism of fats). 8) Bilirubin (heme waste product excreted in the bile). Regulation of bile Secretion ▪ About half the bile secreted between meals. ▪ Flows directly through common bile duct into small intestine. ▪ The rest of bile is diverted through cystic duct into gallbladder to be stored. ▪ CCK from duodenal cells causes contraction of gallbladder and relaxation of sphincter of Oddi 8 Role of Bile Salts in Fat Digestion and Absorption ▪ Emulsifies fats (fat globules are broken into smaller droplets). ▪ Increasing surface area to facilitate enzymatic attack (pancreatic lipase). ▪ Secretion of bile salts is increased by: 1) Hormonal mechanism: Secretin increases secretion of alkaline watery solution from bile cuniculi. 2) Neural mechanism: Parasympathetic stimulation increases bile secretion. 3) Bile salts: Themselves stimulate secretion of further bile. ▪ Bile salts have ability to convert large fat globules into lipid emulsion ▪ Lipid emulsion: many small fat droplets suspended in aqueous chime. ▪ Micelles: are lipid molecules that arrange themselves in a spherical form in aqueous solutions. ▪ Bile salt consists of a lipid-soluble part and water-soluble part. ▪ lipid-soluble part derived from cholesterol. ▪ water-soluble part negativity charged (carboxyl group at end of glycine). ▪ This micelle will absorb into lumen be absorptive cells. Excretion of Bilirubin in Bile. ▪ Bilirubin (yellow color) is waste product formed from breakdown of old RBC. ▪ Doesn’t share in fat digestion. ▪ Excreted by liver cells into bile and finally into intestine. ▪ Some of bilirubin is excreted in urine (giving urine yellow color). ▪ In intestine, bilirubin is modified by intestinal enzymes. ❖ Small Intestine Plays key role in nutrient digestion and absorption (90%). Three segments: 1) Duodenum: Acts as a “mixing bowl”, main function is to neutralize acidic chyme. 2) Jejunum: Has numerous circular folds and abundant, long villi, responsible for majority of chemical digestion and nutrient absorption. 3) Ileum: Control flow from ileum into cecum of large intestine, has few circular folds. ▪ Doesn’t secrete digestive enzymes. ▪ Has adaptations to maximize absorption. ▪ Mucosal lining has large surface area (fingerlike projections called villi). ▪ Villus has a cover of epithelial cells, connective tissue core, capillary network and terminal lymphatic vessel. Small Intestine Motility 1) Segmentation (primary method of motility) ▪ Ring-like contractions of circular smooth muscle along small intestine’s length. ▪ Mix chyme with secretions and slowly move the contents through tract. ▪ Contractions are initiated by BER cells. 2) Peristalsis ▪ Progressive motility that produces forward movement of matter along the GI tract. 3) The migrating motility complex ▪ Between-meal (interdigestive) motility ▪ Consists of weak, repetitive peristaltic waves that move short distance down intestine before dying out. ▪ Starts in stomach and migrates down intestine, Intestinal housekeeper. ▪ Regulated by the hormone motilin. 9 Small Intestine Secretion Brush border enzymes: inserted into microvilli covering. ▪ Enzymatic digestion occurs at surface rather than in the lumen. 1. Enterokinase ➔ activation of trypsin. 2. Disaccharidases: Maltase, sucrase, and lactase disaccharides ➔ monosaccharides. 3. Aminopeptidases ➔ protein digestion. Small Intestine Absorption 1. Na+ absorbed both passively and actively ▪ Energy dependent movement of Na+ ▪ Driven by Na +-K +ATPase pump. ▪ Na+ is pumped from tract lumen into interstitial fluid. ▪ Na+ transport creates an osmotic pressure (water follow sodium as it is absorbed). 2. Water is reabsorbed passively down the osmotic gradient produced by active reabsorption of Na+. 3. Chloride ▪ Passively follows down the electrical gradient created by Na+ absorption ▪ Can be actively absorbed as well if needed. 4. Carbohydrate & Protein Glucose & Amino acids are actively transported into cells of intestinal wall to move into bloodstream. Glucose, Galactose and amino acids linked to Na+ secondary active transport. Fructose is absorbed into blood solely by facilitated diffusion. Amino acids and monosaccharides are actively absorbed into blood. 5. Lipids ▪ Glycerol and fatty acid molecules diffuse into cells of intestinal wall. ▪ Resynthesized into fats, coated with proteins. ▪ Move into lymph vessels (not blood vessels). ❖ Large Intestine ▪ Large bowel consisting of three segments: cecum, colon and rectum. ▪ Colon consists of cecum, ascending colon, transverse colon, descending colon, and sigmoid colon. ▪ Colon receives indigestible food, unabsorbed biliary components and remaining fluid. Large Intestine Motility 1) Haustral contractions: ▪ Slow and non-propulsive, shuffle the contents in a back-and-forth mixing movement. ▪ Similar to small-intestine segmentations but occur much less frequently. ▪ Initiated by autonomous rhythmic contractions of smooth muscle in wall of the large intestine. 2) Mass movements: ▪ Powerful peristaltic contractions. ▪ Stimulated by presence of food in stomach (gastrocolic reflex). ▪ Push colonic contents (feces) into distal part of the large intestine. ▪ 3 to 4 times a day in response to distention of the stomach and duodenum. ▪ Material is stored here until eliminated by defecation. 10 Functions of Large Intestine 1. Absorption of water (1L) and electrolytes (Lacks villi). 2. Absorbing important vitamins generated by bacterial action. 3. Storing fecal material prior to defecation. 4. Secretes alkaline (NaHCO3 mucus solution that protect intestinal mucosa(. Large Intestine Absorption 1. Vitamins ▪ passively absorbed. ▪ Water-soluble vitamins (B & C): are passively absorbed with water. ▪ Fat-soluble vitamins (A K E D): are passively absorbed in micelles. 2. Iron ▪ Some absorbed iron is immediately transported to blood. ▪ Excess iron is stored in ferritin pool. ▪ Unused iron is lost in the feces. 3. Calcium ▪ Most calcium is absorbed by active transport. ▪ About two-thirds of ingested calcium is absorbed. ▪ The remaining one-third is eliminated. Most absorbed nutrients pass through liver for processing and controls their concentration in blood. THE END OF DIGESTIVE 11

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