NPB114 Midterm PDF

How are VIP and secretin related VIP (Vasoactive Intestinal Peptide) and secretin are related because they both belong to the same family of hormones, known as the secretin family, and they work together to aid digestion by regulating activities in the gut: 1. Same Family: Both VIP and secretin...

How are VIP and secretin related VIP (Vasoactive Intestinal Peptide) and secretin are related because they both belong to the same family of hormones, known as the secretin family, and they work together to aid digestion by regulating activities in the gut: 1. Same Family: Both VIP and secretin are part of the secretin hormone family, which means they share similarities in their structure and how they function in the body. 2. Similar Functions: They both help manage the digestive process: ○ VIP relaxes muscles in the gut, increases blood flow to the intestines, and stimulates the release of digestive juices. ○ Secretin tells the pancreas to release bicarbonate to neutralize stomach acid, making the environment in the intestines more suitable for digestion. 3. Coordinated Role: Together, they ensure that digestion runs smoothly by controlling the release of digestive substances and managing how food moves through the digestive tract. In simple terms, VIP and secretin are like teammates in the digestion process, with each helping to make sure the gut is ready to handle and process food effectively. MACRONUTRIENTS & ABSORBABLE UNITS polysaccharides/carbs/disaccharides ○ Starches: polymers of glucose Amylose: alpha 1,4 glycosidic links C-O-C of 2 rings Amylopectin: alpha 1,6 glycosidic links C-O-CH2 of two rings Cellulose: beta 1,4 glycosidic links Same thing but the C-O-C is pointing up In simple terms, alpha linkages have a "down" orientation, making them easy to digest, while beta linkages have an "up" orientation, making them tougher and indigestible for humans. Disaccharides ○ sucrose= glucose+fructose ○ lactose= glucose+galactose ○ trehalose=glucose+glucose Proteins ○ Polymers of amino acids Fats ○ Triglyceride Glycerol and fatty acid  CH2O - CO and CH2 chain ○ Phospholipids Glycerol and fatty acid but one of them has a phosphate group and R group ○ Cholesterol ester Box with O and C=O chain Brief Anatomy of the Tract Single tube Accessory organs attached to the tube Tube Components Oral cavity/mouth ○ Masticate food ○ Chemosensation ○ Mix foodstuff with saliva Esophagus: transit tube Stomach ○ Temporary storage ○ Digestion ○ Regulation of gastric emptying Small intestine/midgut ○ Digestion ○ Receives pancreatic and biliary secretions ○ Absorption Digested nutrients H2O Minerals Vitamins and drugs Large intestine/hindgut ○ Absorbption H2O Vitamins ○ Forms feces ○ Temporarily stores them ○ Behaves as an endocrine gland Accessory organs: produce exocrine secretions Saliva Digestive enzymes  HCO3- Bile secretions ○ Salivary glands ○ Pancreas ○ Biliary system (liver, gallbladder, tubes) Layers of the Tract Serosa ○ Epithelium and connective tissue ○ Connects GI organ to ab cavity ○ Innervated by sensory neurons Pain receptive nociceptors Muscularis externa ○ Muscle contractions ○ Smooth muscle Outer long layer and inner circular layer Long layer contract= shortens Circle layer contracts=becomes smaller ○ Peristalsis: propulsive contraction Moves downstream from oral to aboral ○ Segmentation: mixing contraction Not propulsive (doesn’t move) ○ Has 2 plexi Myenteric plexus: in the middle Submucosal plexus: in between ME and submucosa Brain of GI tract, enteric NS and intrinsic NS Submucosa ○ Connective tissue, lymphatic vessels, and blood vessels Mucosa ○ Lamina propria, lacteals, capillaries ○ Made of epithelium Smooth Muscle Cell Small, single nucleated Not all are innervated Has caveolae, which are invaginations in the plasma membrane of SMC, which handle Ca2+ Dense bodies/bands: strength junctions between cells  ○ Collagen fibers: protective net around muscle cells, keeping them strong, flexible, and well-organized, so they can move and stretch without getting hurt. Transfer force between cells ○ Anchors to actin thin filaments No sarcomeres but thick and thin filaments are present Contractile filaments are organized in any direction Unitary Smooth Muscle Only superficial s.m.c. are innervated AP travel via gap junctions Dense bodies=strength junctions All cells contract at the same time Innervated by efferent m.n. Via varicosities ○ Similar to axon termini Thick filaments-myosin Thin filaments- actin ○ Thick:head and tail ○ Thin: filament (body) To contract you need head of myosin to bind to actin and remove tropomyosin out of the way to form a crossbridge Myosin usually exists as a dimer The light chain (tail) of myosin has to be phosphorylated to form a crossbridge, to then a powerstroke, and force ○ MLCK myosin light chain kinase Move Tropomyosin Out of the Way When calcium binds to caldesmon tropomyosin loses its grip on actin and moves out of the way, allowing cross bridge formation and contraction Excitatory Events ACh ○ ACh binds to mAChR and alpha subunit exchanged GDP for GTP and kicks off beta subunit to make itself active ○ Alpha subunit activates an enzyme called phospholipase C beta (PLC-B), which targets PIP2, digests it, and makes IP3 (lots) with DAG as byproduct IP3 Signaling Binds to sarcoplasmic reticulum to activate it and allow calcium influx to depolarize the cell V gated Ca2+ channels open up and there is a Ca2+ influx from EFC Ca2+ Interacts with SMC caldesmon/calponin: moves tropomyosin out of the way Calmodulin: binds to all 4 ends and becomes Ca-CAM ○ CAM then activates myosin light chain kinase. This phosphorylates the light chain and prepares it for contraction. Inhibitory Events Inhibitory motor neuron and SNS Vasoactive intestinal peptide (VIP) released by inhibitory MN Binds GPCR at plasma membrane of SMC ○ VIP released and binds to GPCR, which takes off beta subunit again and has alpha subunit be activated ○ Alpha subunit activates adenylyl cyclase, which turns ATP to CAMP, which binds to PKA and phosphorylates it ○ pPKA: Prevents Ca2+ influx by keeping VCa2+ channels closed Opens VK+ channels=hyperpolarizes cell Shuts off MLCK Causes muscle to relax, vasodilation Excitatory factors Increase likelihood of GI contraction ○ Ach (major) ○ Serotonin ○ Substance P Inhibitory factors Decrease GI smooth muscle contraction ○ VIP ○ PACAP Pituitary adenylyl cyclase activated peptide Bind to VIP ○ Norepinephrine (neurons), epinephrine (medullary hormone)  Bind to adrenergic receptor From SNS Nitric oxide: released by enteric neurons and MAYBE endothelial cells ○ NO to guanylyl cyclase ○ Turns GTP to cGMP ○ Activates PKG ○ Phosphorylates targets that cause relaxation SMC receive inputs from PNS, SNS, hormones, excitatory and inhibitory enteric MN Pacemaking in the GI Tract 17-19 ft long Contractions differ ○ Stomach 3/min ○ Small intestine 12/min Interstitial cells of Cajal (ICCs) ○ Pacemaker cells ○ Associated with myenteric plexus and smaller plexi among layers of smooth muscle cells ○ Require Kit gene, which encodes a receptor GPCR, which when activating by ligand increases IP3, which opens up V Ca+ channels and creates Ca2+ influx ○ Steel gene encodes stem cell factor ligand to the kit receptor Slow waves electrical activity = B.E.R Neuronal Control of the Tract Intrinsic NS ○ Myenteric and submucosal plexus and smaller plexi Extrinsic NS ○ Autonomic NS SNS PNS Autonomic NS ○ Both branches (SNS & PNS) innervate visceral organs Autonomic efferents ○ Preganglionic neuron Brain stem or spinal cord ○ Postganglionic neuron Innervates organ ○ For excitatory: Preganglionic is longer and post is shorter; work to release ACh  PNS ○ For inhibitory: Preganglionic is shorter and postganglionic is longer; work to release NE SNS Extrinsic sensory neurons ○ Afferent ○ Found in spinal column/dorsal root ganglion ○ Stimulus in small intestine sends info vi dendrite, then to afferent dorsal root, then back to organ via sympathetic preganglionic neuron back to organ to deal with this ○ Spinal afferent/sympathetic Afferent: Detect stretch wall, chemicals in lumen, temp, PAIN, muscle tension Send info to the spinal cord Which controls output via SNS Brainstem: nodose ganglion ○ Detect chemical in lumen, ECF strength, and muscle tension ○ Stimulus in small intestine goes to ganglion in brain stem, back to organ via PNS ○ Vagal afferents Pick up stimuli, send to brain stem Brainstem integrated info, activates PNS preganglionic EFFERENTS Enteric Nervous system: Brains of GI tract Cell bodies, neurons, axons, axonal projection reside within the tract Efferents ○ Motor ○ Involuntary Afferents ○ Sensory ○ Interneurons: integrate the info Types of efferents ○ Motor (enteric motor neurons) Innervate GI SMC +/- ○ Enteric secretomotor efferents Stimulate exocrine cell to release exocrine secretion mucus into the lumen ○ Enteric endocrine efferent Stimulate endocrine cell to release hormone into the capillary ○ Enteric vasodilator efferent  Innervates arteriolar smooth muscle, causes to relax, which increases blood flow to capillaries Afferent sensory neurons IPANS (intrinsic primary afferent neurons) ○ Chemosensitive IPANS Chemicals in lumen and ECF Hypersensitivity: noxious stimulus activates an IPAN, which causes a chain reaction ○ Mechanosensitive IPANs Respond to stretch wall, muscle tension, and distortion to epithelium of mucosa Enteric Interneurons ○ Process info and control enteric efferents ○ Stimulus goes to IPAN then to interneurons then to desired enteric M.N ○ Can be +/- ○ When motor neuron is inhibited it does not fire AP Endocrine Control of the Tract Intestinalfugal fiber: sensory neuron cell body in myenteric plexus that projects out ○ Senses muscle tension ○ Senses muscle tension excited SNS postganglionic efferent to releases NE Inhibits GI smooth muscle Hormones GI tract hormones are all peptides/proteins Precursors are created in the tract All produced by single cells in tract All released into blood to target GI or other tissues like brain Large intestine microflora behave as an endocrine tissue Other hormones that also affect tract ○ Epi ○ Growth hormone ○ Insulin Signaling mechanisms Endocrine: hormone signaling ○ Hormone into blood then to target Paracrine: signal factor ○ Cell releases molecule, short distance to target through ECF Autocrine signaling ○ Released by cell, acts on itself Cell releases it for the molecule to act on itself Hormone Receptors G protein coupled receptors ○ Hormone binds receptor subunit, alpha subunit comes off from beta and exchange GTP for GDP Receptor linked enzymes ○ Tyrosine kinase receptors Ex. insulin receptors Hormone binds in the ECF, receptor is dimerized, protein kinase phosphorylates, receptor dimer is now activated Gastrin Gastrin CCK family G cells in atrium Stimulus: ○ Distension ○ Small peptides aromatic AA ○ No effect by fats or carbs Major effects: ○ Stimulates acid production secretion G34 - feedback involve somatostatin ○ growth/maintenance of gastric mucosa and integrity G17 Minor effects ○ + pancreatic secretions ○ - gastric emptying ○ + bile secretions Cholecystokinin (CCK) (gallbladder contraction and pancreatic secretions) CCK gastrin family Secreted by I cells in duodenum (1ft) and jejunum (8ft) Stimuli ○ Protein (small peptide, aromatic AA) ○ Fats (fatty acids, long in length) ○ No effect by carbs Major effects: ○ Pancreas induces digestive enzyme secretion into small intestine ○ Gall bladder contracts, which expels the biliary secretions into small intestine ○ Bicarbonate production and secretion from pancreas and biliary systems ○ Growth & maintenance by pancreas ○ Regulates gastric emptying Forms  ○ CCK 8 ○ CCK 58 and CCK 83 most common Secretin VIP secretin family S cells in ⅔ of the tract (all 3) Stimulator (in small intestine): ○ Acid ○ Fatty acid ○ Hot pepper Major Effects ○ Bicarbonate increase in production and secretion by pancreas into SI Neutralize chyme acidity ○ Bicarbonate production and secretion by biliary system ○ Pancreatic growth and maintenance Minor effects ○ Inhibits gastric emptying and gallbladder contraction GIP “Gastric Inhibitory Peptide”/Glucose dependent insulinotropic peptide K cells in duodenum, jejunum Secretin VIP family Stimulator: fatty meal Major effects: ○ Inhibits gastric contractions and secretion ○ Induces insulin secretion on a BG dependent relationship Even with low BG it causes insulin secretion >110mg/dL Minor effects: ○ Inhibits hepatic glucose output ○ Inhibits lipoprotein and fat absorption Motilin M cells in duodenum and jejunum Stimulus: fasting ○ Released cycicly Effect: ○ Increases gastrointestinal motility in stomach and SI, which induces fasting motor activity GLP-1 Glucagon like peptide #1 L cells in ileum and early colon Stimulus: meal Incretin  ○ Stimulates pancreas to secrete insulin (major effect) ○ Decreases gastric emptying and contractions which have an effect on pylonic sphincter It will contract ○ Decreases appetite Ex. ozempic Semaglutide bind the GLP1 receptor, reduces appetite and increase in insulin resistance Other Signals Gastric histamine ○ ECL cells ○ Stimulate parietal cell HCl secretion ○ Paracrine ○ Patients with gastric ulcers, sour tummy, treated with H2 receptor blockers like Ranitidine Peptide YY ○ Small distal SI and colon Jejunum and ileum ○ Stimulator: fat ○ Induces: ileal brake Gastric somatostatin ○ D cells in stomach and SI ○ Respond to acidity and lower HCl secretion