GI Session 1 Functional Anatomy & Motility - Lecture Notes PDF

Gastrointestinal Physiology Lecture Dr Silke Kiessling [email protected] Student consultation Monday 13:00-15:00 02AY02 7 sessions on the gastrointestinal (GI) tract and digestion/absorption (also available as shorter podcast from Prof. Robertson) 1a. Stru...

Gastrointestinal Physiology Lecture Dr Silke Kiessling [email protected] Student consultation Monday 13:00-15:00 02AY02 7 sessions on the gastrointestinal (GI) tract and digestion/absorption (also available as shorter podcast from Prof. Robertson) 1a. Structure/function in the GI tract (Today) 1b. Motility and its regulation (Today) 2. Secretion in the GI tract (Tomorrow) 3. Absorption of water and electrolytes (Monday) 4. Digestion and absorption of carbohydrates and proteins (Wednesday) 5. Digestion and absorption of lipids (eLecture) 6. The gut bacteria and healthy colonic metabolism (TBD)  1a) Functional Anatomy of the GI Tract Learning Outcomes 1. The structure of the gut has evolved to be “fit for purpose” based on evolution of our diet 2. It allows us to digest and absorb almost everything we eat 3. To allow this each segment is unique and must function independently 4. The gut has other roles in addition to digestion and absorption Dr Silke Kiessling BMS2077  Overview of the GI Tract The GI tract is a continuous tubular system which forms a physiological barrier between the outside world and the body environment. Approximately 7 metres long in an adult (fairly fixed, independent on body size) Main functions we will cover in these lectures: – Segmental heterogeneity (different parts adapted for different function) – Motility (moving digesta from mouth to anus, allowing for optimal uptake) – Secretion (enzymes, bile salts, fluids for pH, mucus for protection) – Digestion (breakdown of large to small molecules) – Absorption (uptake of nutrients into the enterocyte and ultimately the body)  Anatomical features of the GI system GI tract plus accessory organs, the liver and exocrine pancreas  Stomach Muscular bag; Vary in size from 75ml to 1L Highly adapted for both muscular contraction and secretion Characteristic 4 layered structure of GI tract (uniquely conserved)  Characteristic 4 layered structure of GI tract (uniquely conserved) Mucosa: absorbative surface, blood capillaries, metabolic active part Submucosa: larger blood vessels, heading of to the liver, branches of lymphatic system and ANS Muscularis: double muscle layer, different types of movements and constractions, circular and longitudial Serosa: thick layer of connected tissue for separation, outer covering, bag is called serosa to separate stomach and not the stomach Stomach surface covered in series of pits (small holes) Gastric pits leading to Secretory glands containing multiple cell types Small Intestine (6m) same 4 layered structure; fully adapted for absorption  Small Intestine (same 4 layered structure) lymph vessel villus submucosa circular muscle longitudinal muscle myenteric plexus submucosal Brunner’s plexus gland Small intestinal structure (duodenum/jejunum); surface area is everything Variable between segments enterocyte  Highly vascularised; appears dark red Duodenum Brunners glands (mucus & bicarbonate) Jejunum Long villi absorption increased Large Surface Area absorption increased Ileum Paler appearance (less vessels, less absorption) Peyers patches (lympatics) protection from bacteria Short villi lower level of absorption Smaller Surface Area Other functions of the gut (in addition to digestion and absorption) Gut Barrier function varies between intestinal segments Tight junction prevent molecules passing through the intercellular space between the enterocytes Change in expression of TJ proteins Claudin and Occludin More TJ proteins in ileum Ileum membrane less permeable (prevent bacteria to move across) The gut endocrine system; largest hormone secreting organ  Endocrine-cells 2 types hormone producing cells: Open - clear connection to lumen (direct contact to nutrients) Closed – no connection Highly polarized – hormone containing secretory granules towards basal pole of cell Close to basolateral membrane (BM) Found close to capillary network of lamina propria (rapid appearance in blood). Receptors for neural modulation in basolateral membrane (triggered neurally) Hormones secreted directly by contact with nutrients plus also by stimulation by neuropeptides  Peyers patches form part of GALT (gut associated lymphoid tissue) Located in the lamina propria layer of the mucosa and extending into the submucosa of the ileum. Peyer’s patches catch microorganisms and other antigens entering the intestinal tract by dendritic cells, B-lymphocytes, and T-lymphocytes Peyer’s patches react to dietary proteins Peyer's patches are covered by a special epithelium that contains microfold cells (M cells) direct contact to lumen, linking it to the IS M cells (1) sample antigen directly from the lumen (2) deliver it to antigen-presenting cells  in contact with lumen; lack microvilli M cells Form part of gastrointestinal- associated lymphoid tissue, linking directly to lymphatic system Feature of the ileum & colon Aggregates of lymphoid tissue Increased number of bacteria in distal intestine Backflow of bacteria from colon into sI  Large Intestine - the Colon Decrease in lumen diameter as you move through the colon 1.5 m long, but large lumen size 4 layer structure, but longitudinal muscle in 3 bands, the taeniae coli, gap only circular muscle, evolutionary disadvantage Skeletal and smooth muscle, feacally content due to anus sphincter Crypts are no pits, but wholes (defined as crypt rather than gland) Increased surface area, but colon has no villi (no nutrient absorption) Columnar cells with short microvilli Absorptive cells are most numerous (water absorption) Mucus producing cells for protection Liver Largest of internal organs Closely associated with other accessory organs of GI system Secretion of bile into gall bladder Nutrients and drugs from GI tract drain into hepatic portal vein Short BREAK  1b) Motility and its regulation within the GI Tract Learning Outcomes 1. Different types of contraction in different segments of the gut 2. Luminal distension is key 3. Negative feedback loops 4. Role of enteric nervous system and gut endocrine system Dr Silke Kiessling BMS2077 Motility Controlled movement of food from the mouth to the anus (retrograde movement: vomiting, or rectum in LI) Mixing of food with digestive enzymes and exposure to absorptive surface (main function is digestion & absorption) Motility patterns in: Stomach Small intestine Large intestine Migrating motor complex (unusual pattern when gut is empty) Regulation; neural and hormonal inputs (switch on and off) Stomach Oesophageal peristalsis Reservoir for food (upto 1.5 L) Relaxation of LES Receptive relaxation Basic electrical Rhythm (Interstitial cells of cajal) Regular peristaltic contractions Vigorous contractions Primary Stimulus after a meal is gastric distension  Filling of the stomach Relaxation of fundus; vagovagal reflex; Increase in volume without increase in pressure (~ 1L) Receptive relaxation: funduns dilates when food passes down the pharynx and the esophagus Adaptive relaxation: stomach dilates in response to gastric filling, increases in intragastric pressure Mechanical actions of the stomach Propulsion Construction starts in body moves to antrum Circular muscle at pylorus closes with each gastric contraction but pylorus always 1-2mm open (liquids) Grinding Retropulsion backwards to mix into body Facilitates mixing Small intestinal motility Controlled movements from duodenum to end of ileum frequency gradient of rhythmic contractions in the SI promotes aboral propulsion of the intestinal chyme (stronger and more frequent in duodenum, larger food bolus) Distension is primary stimulus via enteric NS Intestinal slow waves 2 types of movement – Segmentation: mixing with digestive enzymes, surface increased – Peristalsis: propulsive movement of food bolus down the sI Regional motility: construction only where food bolus is (energy efficiency!) construction follow distention Ileocaecal sphincter (opening up to allow processed foods to pass) Segmentation contractions of the circular muscle layer alternate contraction and relaxation of segments mixes chyme with digestive secretions electrical activity generated by pacemaker cells rhythm varies with region of SI Segmentation can be altered by hormones, enteric NS, autonomic NS  Peristalsis circular muscles contract just behind a mass (move bolus forward) pushed into receiving segment where circular muscles are relaxed receiving segment contracts etc bolus moves between 2 and 25 cm/sec (very rapid), but periods of segmentation and then peristalsis (4-5h to get to terminal leum) affected by hormones and autonomic NS destention/peristalsis in the terminal ileum relaxes the ileocaecal sphincter (prevents backflow, bacterial components) Gastro-ileal reflex initiated by gastric motility (to LI)  Large intestine Non-propulsive segmentation in haustra of colon Mass peristalsis: large wave 1/3 of the way (3 segments of longitudinal muscle), so 3 mass peristalsis to move all the way Triggered by: – co-ordinated reflex governed by local distension – control reflex arcs (gastro-colonic reflex) activity and hormones from stomach 72h to move 1.5m of full colon Haustrum (small pouch) Ileum Defaecation Neurally regulated reflex Autonomic (involuntary) and somatic (voluntary) pathways Rectal distension trigger defecation reflex, causes relaxation of internal sphincter and contraction of external sphincter Internal and external anal sphincters (fecal continent) Interdigestive period - the migrating motor complex Very strong sustained contractive activity Cyclic contractile activity which starts in the stomach and travels to ileum, a wave all the way to the terminal ileum Function; to rid GI tract of undigested solids (some species regurgitate these): e.g. owls (this is the sensation you feel when you are hungry) empty gut MMC Phase 1: Quiescence Phase 2: Intermittent and irregular activity sporadic contractions Phase 3: Short-period of intense activity (10 – 30 min) Phase 4: Quiescence Neural Regulation of Motility A. Intrinsic...Enteric Nervous system B. Extrinsic...Autonomic Nervous System (parasymp&symp NS) A. Enteric nervous System 100 million neurons from oesophagus to anus Arranged in 2 plexus in the gut wall: 1. Myenteric Plexus: located between circular and longitudinal muscle layers controls motility, frequency and strength of contraction Sensory neurons are stretch receptors 2. Submucosal Plexus: found within the submucosa Controls secretory cells of mucosal epithelium Sensory neurons are chemoreceptors B. ANS Form neural connections for the ENS. Parasympathetic increases secretion and motility, sympathetic is inhibitory (fight/flight response) Long and short reflexes sensory neuron can project to the CNS or ganglion with the wall of the GI tract CNS External stimulus (sight, smell, taste, though of ENS food) Effector e.g. Internal stimulus contraction of (stretch receptor) smooth muscle Entirely in the gut Effector e.g. contraction of smooth muscle  Example 1: Nutrient Absorption Inhibits Gastric Motility via Gut Hormones 2 1 4 3 Example 2: colonic motility controlled via series of reflexes. Long & short reflexes, CCK & gastrin (stomach hormones stimulate) 1 1. Gastro-colonic reflex (long) Motility in upper gut stimulates motility in lower gut 2. Faeces increases pressure in rectum; defaecation reflex 3. Anal sphincter contracts: rectosphinteric reflex (feces back to sigmoid colon) 3 2 General principles….. All segments have 2 forms of motility (mixing and propulsion) Main stimulus for contraction is distension (ENS) Distension in the region of GI tract immediately before a sphincter causes it to open (usually tonically contracted, barrier for protection) Distension (and absorption) in one “segment” will inhibit contraction and motility in the preceding segment ie SI activity inhibits the stomach, (ENS + gut endocrine system) This makes the gut more energetically efficient Have a go at the “mini-test” on SurreyLearn