2 Digestive System Physiology

Intestinal bacteria (3)

-100 trillion microorganisms= 10x the number of cells found in our human body -> 150-fold more genes than found in the human genome -Microflora is unique and plastic •If you transplant microflora from a fat mouse to skinny mouse, the initially skinny mouse will become fat. •Microflora determines weight, chronic disease risk, etc. •People with different microflora respond to things/drugs differently, even if they are otherwise biochemically the same.

Large intestine: structure (4)

-Appendix- vestigial remnant of a larger cecum -Cecum- absorbs fluids and salts that remain after initial digestion and absorption, and mixes these contents with mucus •Water and salts are absorbed through a thick mucus membrane -Ileocecal sphincter- separates the small and large intestine -Mesentery- folds of tissue that attach organs to the body wall

Bile process (5)

-Bile is made in the liver and transported to the gallbladder where it is stored -When the gallbladder contracts, bile is released into the cystic duct. The cystic duct joins the common bile duct. -Bile aids in lipid digestion via emulsification. Enables large lipid molecules to disperse in the watery environment of the small intestine. -After aiding in lipid digestion, the bile constituents are reabsorbed from the ileum and return to the liver via the hepatic portal vein. -The liver uses these constituents to resynthesize bile, which is then stored in the gallbladder.

Pancreas: intro (2)

-Can separate the roles of the pancreas into endocrine function (i.e. release of insulin) and digestion (i.e. release of digestive enzymes into small intestine). •They are linked. The endocrine functions are important to how the body can utilize the food that was just digested. -Pancreas- releases bicarbonate-rich pancreatic juice that neutralizes chyme, and contains the enzymes needed for digestion of all macronutrients

Pancreas: digestive enzymes (3)

-Carbohydrate digestion: pancreatic alpha-amylase •50% digestion -Lipid digestion: pancreatic lipase •80-90% digestion -Protein digestion: protease •50% digestion -These digestive enzymes are produced by acinar exocrine cells

Stomach: main parts (4)

-Cardia- first portion of the stomach that the food passes into •Gastric juices are manufactured here -Fundus- stores undigested food and the gases released from the chemical digestion of food -Body/corpus- the largest part of the stomach, where the bulk of digestion occurs -Pylorus- bottom of the stomach connected to the duodenum

Cell components: Plasma membrane Cytoplasm Nucleus Rough ER Smooth ER Golgi apparatus Lysosome Mitochondria

-Cell membrane/plasma membrane- cells are surrounded by a phospholipid bilayer that contains embedded proteins, carbohydrates, and lipids •Membrane proteins act as receptors that are sensitive to external stimuli •Also have channels that regulate the movement of substances into the cell -Cytoplasm- the gel-like substance inside all cells that contains organelles, electrolytes, etc. -Nucleus- contains the DNA, which provides coded instructions for protein synthesis -Rough endoplasmic reticulum- series of membrane sacs that contain ribosomes that build and process proteins -Smooth ER- region of the ER involved in lipid synthesis, and lipid trafficking. Do not contain ribosomes so not involved in protein synthesis. -Golgi apparatus- a series of membrane sacs that process and package proteins after they leave the rough ER -Lysosome- contains digestive enzymes that break up proteins, lipids, nucleic acids. Also remove wastes and recycle waste products. -Mitochondria- organelles that produce most of the energy/ATP needed by the cell •There are multiple mitochondria per cell. •The number of mitochondria in a cell depends on the energy needs of the individual cell. •Ex: muscle cells are more enriched in mitochondria. •The number of mitochondria can be changed. •Ex: if you enter a metabolic state where nutrient needs increase then the production of mitochondria can be induced to meet new nutrient needs.

Digestion (4)

-Chemical breakdown of nutrients -Occurs in the lumen and at the brush border -Most occurs in the small intestine -It is accomplished through enzymes with help from bile

Liver: structure (4)

-Divided into left lobe and right lobe. Upper lobes are where bile is produced. -Cystic duct- short duct that joins the gallbladder to the common bile duct -Right hepatic bile duct- right and left hepatic bile ducts converge into common bile duct -Sinusoids- location for the mixing of oxygen-rich blood from the hepatic artery and nutrient-rich blood from the portal vein

Stomach: endocrine G cells (5)

-Endocrine G-cells produce gastrin. Main function of gastrin is to stimulate parietal and chief cells. -Gastrin stimulates digestive activities and the secretion of HCl, which is needed for the absorption of vitamin B12 •HCl functions: converts pepsinogen to pepsin, denatures proteins, releases nutrients from organic complexes, acts as bactericide -Increases gastric motility and emptying •Liquids, carbs, low-fiber, low-calorie foods exit the stomach faster •High fiber, fat, protein foods exit slower and keep you feeling full longer -Digestion of carbohydrates stops because there are no carbohydrate digesting enzymes present in the stomach. •There are no enzymes for carbohydrate digestion because the stomach acid denatures those enzymes -Protein digestion begins •Chief cells that line the gastric glands produce inactive pepsinogen, which is converted to active pepsin via hydrogen. Pepsin then hydrolyzes proteins into peptides and some amino acids.

Pancreas: juice contents and pH

-Enzymes, electrolytes, bicarbonate -pH of pancreatic juice = 8.6. it is alkaline due to the high concentration of bicarbonate ions. This is used to neutralize the low pH of the chyme coming from the stomach.

Contents of gastric juice (4)

-Enzymes: pepsin, amylase, lipase -HCl: converts pepsinogen to pepsin, denatures proteins, releases nutrients from organic complexes, acts as bactericide -Mucus -Intrinsic factor. This is a specific protein-like component that is needed for the absorption of B12. •The intrinsic factor is produced in the stomach, but it is not utilized until the small intestine.

Esophagus (4)

-Food is called a bolus. This term is used to refer to food that is broken down mechanically, underwent some enzymatic digestion by amylase, and is coated in mucus. -Transports food from the pharynx to the stomach -Muscular action •Rhythmic contractions called peristalsis move the bolus toward the stomach •Circular muscles contract to condense the bolus. •Longitudinal to propel the bolus down. •The esophagus only uses muscular action. No secretory action. -Sphincters on both ends. •If the lower esophageal sphincter/gastroesophageal sphincter opens too often or does not close tightly enough, stomach acid can seep into the esophagus and cause a burning sensation

Stomach: ghrelin (4)

-Ghrelin- the hunger hormone -When the stomach is empty, ghrelin is secreted. -When the stomach is full, secretion stops. •It acts to both increase hunger and increase gastric acid secretion to prepare for the arrival of food. -Secretion can be stimulated when foods are present but don't offer enough calories Ex: sugar free beverages and snacks The body has evolved to associate a sweet taste with caloric intake (think fruits). There is a discrepancy between the sweet taste of the drink and no glucose/energy from the drink. The body is expecting the arrival of calories though it does not necessarily need them. Ghrelin is released and activates hunger pathways in order to acquire the energy that it is expecting. Diet sodas actually make you hungrier, thereby leading to an increased intake of food and more weight gain than taking the calorie hit from a regular soda. Sugar free alternative and fat replacements don't allow you to stay full for as long. This is especially true of protein shakes because they have artificial sweeteners + no fiber + already in liquid form so less to digest.

What does HCl do? (5)

-HCl denatures proteins from tertiary to secondary structures •The degradation of proteins renders them non-functional since a protein's structure determines its function. -HCl also functions to make the pH of the stomach acidic -Bactericide -Convert inactive pepsinogen to active pepsin -Needed for vitamin B12 absorption

Small Intestine Structure (5)

-High SA:V ratio •Multifolded arrangement •Villi •Microvilli (brush border) -It is highly vascularized so the blood and lymph vessels can readily absorb nutrients and transport them through the body. -Villi regulate absorption based on needs -Microvilli have enzymes and pumps •Microvilli have enzymes anchored in their apical plasma membrane. This final stage of digestion happens right in the immediate vicinity of transporters. •Plasma membranes of the microvilli contain pumps that use ATP to actively transport molecules across a membrane. -Enterocytes- specialized absorptive cells that are the predominant epithelial lining •These cells are specialized for absorption of nutrients across the apical plasma membrane. •They then export the nutrient across the basal plasma membrane. •Upon release, nutrient molecules diffuse into connective tissue space and eventually into capillaries or lacteals.

Regulatory peptide control of GI Tract (2)

-Hormones: secretin, CCK, ghrelin -Paracrine signalling- a form of cell-cell communication in which a cell produces a signal to induce changes in nearby cells •Different from endocrine factors like hormones because paracrine factors diffuse over a short distance to cause local action

Large intestine (3)

-Large intestine- receives and prepares undigested food to be eliminated from the body as feces. This is done by removing extra fluids so that unabsorbed materials can be released as waste. •Uptake of water, vitamin K, biotin -Gut bacteria are present all along GI tract, but the greatest concentration is found in the large intestine. -Intestinal bacteria partially break down fiber, 2kcal/g

Stomach: curvature

-Lesser curvature- forms the right border of the stomach and extends from the cardiac orifice to the pylorus. •Function: gives attachment to the two layers of the hepatogastric ligament (lesser omentum) -Greater curvature- is much longer than the lesser curvature and extends from the left of the cardiac orifice, over the dome of the fundus, and along the left border of the stomach to the pylorus. •Function: attachment to the gastrolienal ligament and the two layers of the greater omentum

Oral Cavity Goals (4)

-Mechanical breakdown of food -Initial enzymatic digestion -Prepare food for travel through the upper GI tract -First-line immune defense

Small intestine: structure (6)

-Mucosa and submucosa are arranged in circular folds of Kerckring -The circular folds are covered with villi. Each contains a capillary network and a lymphatic vessel/lacteal. •Lacteal supports movement of immune cells and helps us absorb fat. •Crypts of Lieberkuhn- cells in these crypts will migrate up to eventually become the cells of the villus -Each villus is made of absorptive cells called enterocytes •Enterocytes- cells lining the border of the intestine. -The enterocytes have microvilli, which make up the brush border and increase SA •The other side of the enterocyte is implanted. •These structures of the enterocyte function together to facilitate movement toward capillaries. -There are very specialized receptors and enzymes specific to absorption. So, they body is picky about what enters the body. -Glycocalyx- In general, it is a glycoprotein and glycolipid that covers and surrounds the cell membranes of some bacteria, epithelial cells, etc. •Used to distinguish between body's own tissue and healthy tissue. •In the intestine, it is found on apical portion of microvilli, and the projections are acidic mucopolysaccharides and glycoproteins. •Function: additional SA + has enzymes needed for the final steps of digestion of proteins and sugars

Neural Regulation of GI Tract (2)

-Myenteric plexus - peristalsis, motility •Major nerve supply to the GI tract •Nerves are derived from those of the parasympathetic nerves around the superior mesenteric artery. -Submucosal plexus - secretions, local blood flow •Lives in the submucosa of the intestinal wall. The nerves of this are derived from the nerves of the myenteric plexus.

Utilization of exogenous nutrients (3)

-Nutrients are essential but cannot be synthesized by the body, so they must be obtained exogenously -Bioavailability- the degree and rate at which a substance (e.g. nutrient or drug) is absorbed into a living system and/or is made available at the site of physiological activity -Primary determinants of nutrient utilization •Digestion- breakdown of chemical substances •Absorption- transfer of nutrients from outside environment to inside i.e. inside intestine. So, this refers to the physical transfer across barrier of intestine into circulation. •Transport- circulation throughout the body

Intestine: muscular processes (7)

-Occur mostly in the duodenum -Segmentation- contractions/relaxations of the circular muscle to create a "chopping" motion •This allows chyme to move in both directions and thus allows for a greater mixing of the contents of the intestines •Segmentation allows for peristalsis -Peristalsis- series of wavelike rhythmic contractions and relaxations involving both the circular and longitudinal muscles •Function: propel food toward the GI tract Sphincters -Pyloric sphincter- a band of smooth muscle at the junction of the pylorus of the stomach and duodenum of the small intestine •Plays an important role in controlling the rate of digestion and the direction of chyme movement •It prevents regurgitation of chyme from the small intestine to the stomach •It also ensures that chyme moves from the stomach to the small intestine such that the small intestine receives a manageable volume of chyme from which to absorb nutrients. -Ileocecal valve- a sphincter muscle that separates the small and large intestines •Functions to limit the reflux of colonic contents into the ilium •It is distinctive because it is the only site in the GI tract that is used for vitamin B12 and bile acid absorption -Rectal muscles/anus- flow of feces through the anus is by control of the anal sphincter valve -Control of sphincters can be disrupted by drugs, high fiber foods without enough water intake

Intestine: secretory processes (2)

-Occur mostly in the duodenum -Secretions from the pancreas, liver (accessory organs)

Pancreas: medical conditions

-Pancreatitis- inflammation of the pancreas. It is difficult to consume food because the digestive enzymes typically produced in the pancreas are not being produced. The individual must take enzyme supplements. -Pancreatic cancer- cancer that is particularly aggressive and hard to treat With cancer, there are greater nutrient needs by the body, but the source of the ability to use these nutrients (the pancreas) is what is being affected by the cancer.

Liver: functions (3)

-Production of bile -Detoxify alcohol, drugs, etc. -The central hub for all things metabolism. It dictates what the rest of the body sees after ingesting certain food items.

Oral cavity Salivary glands (6)

-Salivary glands- accessory organs that release a mixture of water, mucus, and enzymes -6 salivary glands in total, 3 on each side. •Parotid are the largest. -Salivary glands release saliva, which begins the digestion of carbohydrates. Amylase breaks amylose (starch) down into maltose and dextrin. -Saliva also has very small amounts of salivary lipase but most lipid digestion occurs in the small intestine. -The watery mixture is used to moisten food so that it can be moved around the mouth by the tongue -The substances in saliva protect against tooth decay and enamel disruption. Saliva prevents dental caries and degradation of mouth structures by coating the teeth while you chew.

Ways nutrients can be absorbed (5)

-Simple diffusion- substance passes through a membrane without any aid •Hydrophobic small molecules -Facilitated diffusion (passive-mediated transport)- the process of spontaneous passive transport across a biological membrane via specific transmembrane integral proteins •Polar and charged molecules •Channel proteins are open pores that allow for the passage of any molecule of appropriate size •Carrier proteins bind to one specific molecule on one side of the membrane, undergo a conformational change to allow the molecule to pass through the membrane and be released on the other side -Active transport- movement of molecules against their concentration gradient (low to high concentration) involving the use of ATP -Pinocytosis- the ingestion of liquid into a cell by forming pinosomes, which then pinch off the plasma membrane •Essentially, engulfing the membrane without needing a protein or receptor -Mechanism of absorption utilized depends on solubility (fat vs. water), concentration or electrochemical gradient, size of molecule.

Stomach: muscular action (5)

-Thick walls, 3 layers of muscles: circular, longitudinal, diagonal •This prevents stomach acid from escaping to other sections of the body. -Strongest muscles in the body •Forceful contractions of these muscles enable food to mix with gastric juices to form chyme -Timing the release of chyme. Chyme is used to refer to the bolus of food + stomach acid. It is called chyme from this point on. •Chyme is released from stomach to duodenum via pyloric sphincter -Peristalsis •Occurs over the entire length of the GI tract •Stomach peristalsis dictates the rate at which foods leave the stomach •Slow peristalsis occurs when a high fiber or high protein meal is consumed. This is because protein digestion takes a long time, and fiber digestion does too. The stomach can't digest the fiber but the mechanoreceptors detect its presence and attempts to break it down somewhat via physical churning of the food (not true digestion though) -Rugae- folds in the lining of the stomach that flatten when the stomach fills with food to allow the stomach the expand

Structures of the GI tract (6) Highly__ Lumen Mucosa Submucosa Muscularis externa Serosa

-This is a highly muscularized, highly vascularized organ -Lumen- center of intestinal muscle •Note that this is not considered the "inside" of the GI tract. Food is not truly "inside" until it is in the cells. •This contains the nutrients/food that is moving through it. •The microbiome is also contained here -Mucosa- the innermost membrane layer that produces and releases secretions needed for digestion •This layer directly interacts with food and nutrient components. It is responsible for releasing secretions needed for digestion and for transport of cells. •Contains lymphoid tissues that protects the body. This is important for fighting off pathogens before they enter the cells and cause more serious consequences. •Ex: food poisoning -Submucosa- connective tissue that contains blood vessels, lymphatic vessels, nerves, and lymphoid tissue -Muscularis externa- two layers of smooth muscle (longitudinal and circular). This is responsible for GI motility. •The circular muscles that surround the luminal shape play a key role in forcing food through the GI tract. -Serosa- has connective tissue and strong vascular network •Functions: provide external coverage and protection, retain muscular layers

Small intestine: junctions (3)

-Tight junction- closely associated area between 2 cells that is virtually impermeable to fluid -Desmosome- link adjacent cells together by cytoskeletal filaments and cadherins, anchors the junction -Gap junction- directly connect the cytoplasm of 2 cells, which allows various ions, electrical impulses to pass between the 2 cells

Contents of saliva (5)

-Water: universal solvent -Electrolytes -Mucus: protects GI cells from being damaged by the food that is eaten -Enzymes. Main enzyme is salivary amylase, which hydrolyzes alpha 1,4 glycosidic linkages in starch -Antibacterial and antiviral compounds

Gallbladder (3)

-stores, concentrates, and releases the bile needed for lipid emulsification -Bile is recycled. It is released into the small intestine for fat emulsification, but it is later reabsorbed and cycled back. •If something can't be broken down all the way and absorbed, the body rejects it. This is commonly associated with diarrhea. -Gallbladder surgery: without the gallbladder, it is difficult to breakdown fat. The liver will continue to produce bile without a gallbladder, but since there is nowhere for the bile to be stored, the bile synthesis rate in the liver drops significantly. •Since bile production is downregulated, patients must follow very low-fat diets.

Nature of most stomach digestion

Mechanical -Proteins are unfolded from complex structures to a more primary structure. •This is important because there is greater access to the protein by enzymes. -These proteases have a specificity for operating at a low pH and aren't destroyed by the stomach acid.

First nutrients to be absorbed?

Micros

Stomach, 1 sentence definition

Muscular contractions mix food with acid and enzymes, causing the chemical and physical breakdown of food into chyme

Span of nutrient metabolism

Nutrient metabolism spans organismal, tissue, and cellular levels

Stomach: pacemaker, antrum

Pacemaker: -saddle shaped area in the greater curvature of the stomach that regulates the frequency of gastric contractions -Patients can receive temporary electrical stimulation and surgically implanted permanent pacemakers to help control chronic stomach problems i.e. severe vomiting in diabetes patients •It doesn't act locally, it somehow acts on the brain's center for nausea and vomiting by activating the neural pathways running from the stomach to the brain Antrum -antrum is a general term for cavity or chamber •Pyloric antrum (AKA "antrum")- initial portion of the pyloric part of the stomach •Pylorus connects stomach to duodenum. The antrum part is the opening to the body of the stomach.

Pancreas: secretin (2) and CCK (2)

Secretin: -Presence of chyme stimulates the duodenum to release secretin -Secretin then stimulates pancreatic secretion of bicarbonate to increase the pH Cholecystokinin (CCK): -Stimulated by fat in the intestines -Stimulates fat emulsification and slows down motility

Pharynx

propels food from the back of the oral cavity into the esophagus