ANSC 311 - Midterm 1 - Lecture 4-5

Oropharyngeal phase

Phase of Swallowing

• Bolus pushed back by tongue acting on pressure receptors 

• Tongue stops return to mouth 

• Uvula blocks nose 

• Glottis and epiglottis blocks access to lungs 

• Swallowing centre (in the medulla) coordinates and inhibits respiratory centre 

  • Can’t breath once starting swallowing process

• Pharyngoesophageal sphincter opens 

  • Top of esophagus relaxes and opens

Oesophageal phase

Phase of Swallowing

• Peristaltic wave (5-9s) 

  • Directional action

• Skeletal muscle (involuntary in this case) 

• Oesophagogastric/cardiac sphincter opens 

  • Top of stomach opens

Peristalsis

• Directional Movement

• Waves of contraction 

• Gradually works its way down, contraction and relaxation of muscle

  • Longitudinal muscles and circular muscle - alternate between contraction and relaxation

• Rapid propulsion 

• Programmed by enteric nervous system

• Occurs in stomach and somewhat in small intestine

Fundus

Gastric Motility in ______

• Receptive relaxation (makes room) 

  • In a fasted state, stomach is small, so nitric oxide and VIP induces stomach to relax and make room for food to enter

  • NO (nitric oxide) and VIP (vasoactive intestinal polypeptide) involved in relaxation 

    • Induced by ACh

Corpus

Gastric Motility in ______

• Mixing vat for saliva, food, and gastric secretions

Antrum

Gastric Motility in ______

• Propulsion of food through the pyloric sphincter to the duodenum 

  • Peristalsis begins working against closed sphincter

  • Eventually get signal that duodenum can take food and pyloric sphincter open

• Size discrimination 

• Controlled by 

  • Distension 

  • Parasympathetic

• Stomach stretch

• Parasympathetic

• Gastrin

Factors that increase gastric emptying (3)

• Chemo, osmo, mechanoreceptors

• Sympathetic

• CCK, gastrin inhibitory peptide, secretin

Factors that decrease gastric emptying (3 - 7)

Segmentation

• Non-directional movement

• Most common form of motility 

  • Contraction of circular muscle 

  • Not propagated in one direction 

• Alternating contractions 

  • Results in mixing 

• Frequency decreases distally 

  • Duodenum 12/min 

  • Ileum 9/min 

  • Colon 2/h 

Haustration

Segmentation in the colon

Gastro-ileal reflex

Response of Motility Regulation

• Stimulates segmentation in ileum 

• Inhibits ileo-caecal sphincter (opens) 

  • Sphincter between small and large intestine

  • Even though not directional, sphincter is open, so stuff moves in

Gastro-colic reflex

Response of Motility Regulation

• Mass movements in colon - defecation

Tonic contraction

• Sustained contraction of muscle

• Divide GIT into functional segments 

• Examples 

  • Esophageal sphincter

  • Pyloric sphincter 

  • Ileocecal sphincter

Interstitial cells of Cajal (ICC)

• Pacemakers in circular and longitudinal muscle layers in special nerves

• Set an electrical rhythm in intestinal tract

• Different based on part of intestine

• Create a pulse - not strong enough to cause muscle contraction

• Need additional stimuli, acetylcholine, to come in and cause muscle contraction

  • Allows it to surpass threshold and cause an action potential

Acetylcholine

Regulator of Basic Electrical Rhythm of GIT

• Parasympathetic

• Increases the resting basal membrane potential, and stimulate action potentials and contraction 

Norepinephrine

Regulator of Basic Electrical Rhythm of GIT

• Sympathetic

• Decreases the resting basal membrane potential, and prevent generation of action potentials and contraction

  • Increases threshold that must be met to cause AP

Segmentation reflex

Small intestine motility - Fed State

Peristaltic activity

Migrating Myoelectric Complex (MMC)

Small intestine motility - Fasting State

Medulla

Vomiting center in the brain is located in the ______

• Pharyngeal stimulation

• Gastric irritation (ipecac, cytotoxins, etc.)

• Chemoreceptor (hormones, drugs)

• Motion sickness

• Pain/sights/anticipation

Causes of vomiting that activate vomiting center of medulla (5)

Myenteric plexus

Part of Enteric Nervous System

• Between circ. and long. smooth muscle 

  • Between muscle layers

• Extensive, long interneurons 

• Activated by sympathetic and parasympathetic NS

  • Parasympathetic

  • Sympathetic

Submucosal plexus

Part of Enteric Nervous System

• Interneurons minor 

• Only parasympathetic activation

norepinephrine

Under sympathetic control postganglionic neurons release ________ to inhibit digestion

acetylcholine

Under parasympathetic control postganglionic neurons release ________ to promote digestion

Ileus

• Drugs used during surgery can impact motility of GIT and lead to a blockage

  • Start having extra motility above to push it through

  • Starts to stretch

  • Only feel pain associated with it after GIT tries to manage it on its own

  • If blocked too long leading to distension then sympathetic reflex enters CNS resulting in pain

Endocrine

Type of Control of GI Function

• Released into general circulation

• Specificity is a property of the target tissues

• Specific receptors are present

• Examples (gut hormones are peptides)

  • Gastrin 

  • Secretin

  • Cholecystokinin (CCK)

  • Motilin (impacts motility)

Paracrine

Type of Control of GI Function

• Released from endocrine cells and diffuse through extracellular space to their target tissue

• Somatostatin (D cells) inhibit gastrin release (G cells)

Autocrine

Type of Control of GI Function

• A released substance regulates the cell’s own function

Neurocrine

Type of Control of GI Function

• Sensory cells secrete neurotransmitters

Gastrin

Peptide Gut Hormone

• Produced in stomach and duodenum primarily

• Peptides, AA

Stimulates:

• Gastric secretion

• Mucosal growth

GIP

Peptide Gut Hormone

• Active in stomach and small intestine

• Stimulus = Glucose, AA, FA

Inhibits:

• Inhibits gastric secretion

• Also known as glucose-dependent insulinotrophic polypeptide

  • Main role is stimulation of insulin production (incretin)

CCK

Peptide Gut Hormone

• Not produced in stomach, but throughout small intestine

• Fatty acids, AA

• Induces bile secretion (causes contraction of gallbladder)

• Acts on acinar cells to secrete digestive enzymes

• Matches nutrient delivery to digestive capacity

• Inhibits stomach from sending more food down into small intestine - keep pyloric sphincter closed

• Induces bile secretion (causes contraction of gallbladder)

• Acts on acinar cells to secrete digestive enzymes

• Regulates sphincter of Oddi

Stimulates:

• Pancreatic enzyme secretion

• Gallbladder contraction

Secretin

Peptide Gut Hormone

• Responds to acid

• Active throughout small intestine

• Acts on duct cells of pancreas to release more base

Stimulates:

• Pancreatic HCO3 secretion

Hydrophilic

________ Hormones

• Signaling Cells:

• Hormone stored in intracellular vesicles

• Hormones released by exocytosis

• Target Cells:

• Attach to trans-membrane cells

• Amplify signals via second messengers

  • Things such as G-coupled receptors

  • cAMP, Ca2+, IP3

  • Activate existing enzymes

• Rapid biological effects

Hydrophobic

________ Hormones

• Signaling Cells:

• Hormone synthesized on demand

• Hormones released by diffusion

• Target Cells:

• Diffuse and attach to intracellular receptors 

• A hormone-receptor complex binds to target gene

• mRNA transcription is altered

• Slow, but more sustained biological effects

Glucagon-like peptide 1

Peptide Gut Hormone

• Produced by L-cells in the intestinal ileum and colon in response to nutrients and short chain fatty acids (made by microbes)

• Enhances insulin secretion

• Inhibits gastric emptying and motility (ileal brake)

• DPP IV (expressed in endothelium) degrades/inactivates

• 2 minute half-life

Glucagon-like peptide 2

Peptide Gut Hormone

• Acts more locally

• Produced by L-cells in the intestinal ileum and colon in response to nutrients and short-chain fatty acids

• Matches nutrients to intestinal replacement

• Improves intestinal integrity

• Increased permeability of cells

• Inhibits loss of cells (apoptosis)

• Decreases permeability (acts on tight junction proteins)

• Decreased motility

• Important for growth of the entire gut

Ghrelin

• Hunger hormone

• Produced by cells of the fundus of the stomach and epsilon cells of the pancreas

• Stretch inhibits secretion

• Increases hunger, gastric secretion, and GIT motility

• Positively regulates AgRP/NPY neurons

stretch, CCK, nutrient receptors in liver, PYY, GLP-1

GIT Factors that regulate Satiety

• Stimulate vagus nerve

leptin, insulin

Non-GIT Factors that regulate Satiety

Leptin

• Peptide hormone produced and secreted by adipocytes

• Acts on the hypothalamus (arcuate nucleus) to reduce hunger

• Acts on fat reserves:

  • Inhibits feeding

  • Inhibits fat synthesis

  • Stimulates beta-oxidation of fatty acids

• Stimulates sympathetic nervous system

  • Increase blood pressure

  • Increase heart rate

  • Thermogenesis, via effects on adipose

POMC/CART neurons

Neurons of the Arcuate Nucleus

• Drive anorexic signal

• Positively regulated by insulin and leptin

• Reduce consumption

AgRP/NPY neurons

Neurons of the Arcuate Nucleus

• Drive orexic response

• Negatively regulated by insulin and leptin

• Positively regulated by ghrelin

• Increase consumption 

NPY

Neurotransmitter involved in homeostatic regulation of food intake

• short neuropeptide isolated from the hypothalamus and resembling peptide YY produced by the digestive tract

AgRP (agouti-related protein)

Neurotransmitter involved in homeostatic regulation of food intake

• Sequence similarity with Agouti signaling peptide, a peptide, a hormone that controls coat pigmentation in Augoutis (rodents). Acts as an antagonist of the melanocortin-3 and -4 receptor (blocks action of α-MSH)

  • Get agouti pigmentation and improper regulation of feed intake

Insulin

• A rise in blood sugar level after a meal stimulates the pancreas to secrete _____

• In addition to its other functions, insulin suppresses appetite by acting on the brain

PYY

• Hormone ____ secreted by the small intestine after meals

• Acts as an appetite suppressant that counters the appetite stimulation of ghrelin

Leptin

• Produced by adipose (fat) tissue

• Suppresses appetite as its level increases

• When body fat decreases, ____ levels fall, and appetite increases

Ghrelin

• Secreted by the stomach wall

• One of the signals that triggers feelings of hunger as mealtimes approach

• In dieters who lose weight, ____ levels increase which may be one reason its so hard to stay on a diet