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Gastrointestinal System (Structure (Long epithelium filled tube
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Gastrointestinal System
Structure
- Long epithelium filled tube
- Functional sections separated by sphincters
- Connected to accessory exocrine glands
Organs:
- Mouth
- Esophagus
- Large Intestine
- Pharynx
- Stomach
- Small Intestine (Dudodenum, jejunum and ilium)
- Anus
Sphincters:
- Sphincter of Oddi
- Upper oesophageal sphincter
- Lower oesophageal sphincter
- Pyloric sphincter
- Anal sphincters
- Ileocecal valve
Glands:
- Sublingual salivary glands
- Submandibular salivary glands
- Liver
- Gallbladder
- Parotid salivary glands
- Pancreas
Function
-
Secretion:
- Maintains environment for digestive function (enzymes, water, salt)
Digestion:
- Mechanical and chemical processes that break down food
Absorption:
- Uptake (or reuptake) of nutrients, salts and water into the body.
Tract Wall
- Lumen
- Epithelium (secretion and absorption)
- Mucosa (secretion and absorption)
- Submucosa (transport nutrients and controls epithelia
- Muscularis externa (motility/control of motility)
- Serosa
Epithelia:
- Selective barrier of polarised cells
- Tight junctions control movement
- Membranes control movement through.
Small Intestine Epithelia:
- Replaced every 5 days
- Absorptive cells in contact with the intestinal contents
- Secretory cells in crypts or glands, protection from infection
- Stem cells + Paneth (immune)
Small Intestine Mucosa:
- Plicae circulares
- Villi
- Microvilli
- Blood + Lymphatics: Carry nutrients
- Muscularis mucosa: Villus movement
- Submucosal plexus: neural control of secretion, absorption and peristalsis/segmentation
Blood Supply
Macroscopic:
- 25% CO at rest
- Increased blood flow after eating
- Venous return, via liver allows removal of toxins.
Microscopic:
- Blood + lymph vessels carry nutrients to and from the submucosa
Dense capillary beds penetrate:
- Mucosa of stomach and LI
- Villi of SI
- Crypts of SI
Regulation
Homeostasis:
- Controlled Variable = conditions in the GIT lumen
- Receptors = special senses, chemo/osmo/mechanoreceptors
- Signal Pathways = neural and hormonal
- Effectors = GIT smooth muscle and epithelial cells
CNS Regulation:
- Integration of responses to external stimuli
- Sympathetic: reflexes that generally inhibit GI function (noradrenaline/epinephrine)
- Parasympathetic: reflexes that stimulate GI function
- Response to GI lumen (internal stimuli)
ENS Regulation:
Response to internal stimuli
- Receptors detect conditions in GI tract (stretch, chemical)
- ENS Response: occurs via 2 short reflex pathways.
- Myenteric Plexus Pathway: longitudinal and circular muscular layers, motor neurons to these control motility
- Submucosal Plexus Pathway: Between mucosa and circular muscle layers, secreomotor neurons to glands, epithelia, muscularis mucosa controls secretion.
Hormonal Regulation:
Response to internal stimuli
- Receptors = chemo, Oslo, mechanoreceptors
- Enteroendocrine Cells: in epithelial layer, exposed and respond to luminal contents, basolateral = secretory granules.
- Effectors = multiple sites of action.
Submucosal Plexus
Myenteric Plexus
- Controls the muscularis (motility)
Neuron Types
- CNS (PNS and SNS and Sensory)
Enteric Nervous System
- Mechano/Chemo receptors, interneurons, efferent neurons (motor and secretory), interstitial cells of Cajal (pacemakers of GI)
Phases
Cephalic Phase
- Detects food (sight, smell, taste)
- Prepares the GIT lumen for food CNS via ENS
Gastric Phase
- Detects: distension, pH, nutrients
- Sends signals via ENS, CNS or hormones
- Digestion
Intestinal Phase
- Detects: stretch, acid, osmolarity, nutrients
- Sends signals via CNS, ENS and hormones
Smooth Muscle
GI Smooth Muscle
- Electrically = gap junction
- Physically = adherins
- Cells act as single unit
Contraction Patterns:
- Phasic; contract/relax over seconds - peristalsis
- Tonic; sustained contraction mins to hours e.g. sphincters
Phasic Contractions:
- BER or slow wave contractions
- All GI muscle exhibits
- Spontaneous depolarisation and depolarisation in a cycle
- Potential reaches threshold = APs occur, because cells are coupled they contract together
Pacemaker Cells = Interstitial Cells of Cajal
- Generate slow electrical waves
- Set frequency, no change.
- FORCE depends on amount of time spent above threshold
- Linked to other interstitial cells
- Found in myenteric plexus, submucosal plexus
- SNS = decrease
- PNS = increase
-
- Can be spontaneously active with patterns over time
- Can be coupled together electrically
-
Absorption
Minerals
Ca2+
- Actively absorbed in duodenum
- Apical Ca channels
- Intracellular carrier proteins
- Basolateral CaATPase
Fe2+
- Actively absorbed in duodenum
- Cotransported with H+ DMT-1
- Exported by ferroportin
Electrolyte
- Changes based on amount of salt in the diet
- Normal salt = electroneutral
- Depleted salt = electrogenic
Electroneutral Na+ Absorption
- CA generates HCO3 and H+
- Apical NHE-3 exchanges
- Cl- absorbed transcellularly
- NaCl causes flux
Electrogenic Na+ Absorption
- Apical Na entry via ENac
- Exits via Na/KATPase, creates net charge transfer
- Cl follows paracellular path
- Water follows salt, relies heavily on transcellular flux
Aldosterone
- Released in response to low blood pressure
- Acts on colon and kidney to increase Na absorption
- Binds to gene promoters in colon epithelial cells to stimulate protein synthesis
- Increases electrogenic Na+ absorption
SCFA Absorption:
- Produced by colonic bacteria
- Can reach [100-150]mM
- Absorbed via SMCT transporter
- No basolateral transporter as are Abe used as energy source for colonocytes
Secretion
Cl Secretion
- Occurs in all segments
- The dude establishes gradient
- Cl uptake via NKCC1
- Cl moves out of apical membrane via CFTR channel
- Drives paracellular Na and Water movement
Regulation:
- Secondary messengers stimulate secretion
- cAMP stimulates CFTR activity, sustained response.
- Ligands = VIP and prostaglandins
- Ca stimulates K+ channel activity which increases driving force for NKCC and Cl- exit
- Ligands = ACh and histamine
HCO3 Secretion
- The dude establishes gradient
- HCO3 uptake via basolateral NBC
- HCO3 moves out apical via Cl- couple transporter, CFTR recycles Cl-
- Drives paracellular Na and H2O movement
-
Jejunum
- Main site
- Efficient due to large SA
Nutrient Absorption
Carbohydrate
- 200-300g per day (50%)
- Only monosaccharides absorbed
- Poly: 70% of ingested CHO
- Di: 30-40% ingested CHO
- Mono: 5-10% ingested CHO
Luminal Digestion
- Salivary a amylase
- Minimal digestion
- Hydrolyses 1-4 bonds
Disaccharidases:
- Transported to apical membrane
- Break disaccharides into monosaccharides
- Proximity to transporters
Lactose Intolerance:
- Lactase required, produced as infants
- Genetic variability in lactase persistence
- Milk ingested from other species without lactase persistence = undigested lactose.
- Decrease L absorption = decrease water absorption + diarrhoea .
- L used as substrate by colonic bacteria
Absorption:
- Na+ dependent: apical SGLT1, basolateral GLUT2
- OR Na+ independent: apical GLUT5, basolateral GLUT2
Fats
- High energy content
- 100g per day
- 90% TAGs, 10% other fats
Step 1: Emulsification
- Increases rate of TAG digestion
- Amphipathic bile salts
- Retropulsion: crude emulsion
- Segmentation: stabilised emulsion
Step 2: Enzyme Digestion
- Intestinal lumen
- Collapse binds to emulsion droplet
- Interacts with lipase
- Lipase hydrolyses TAGs at surface
- Stabilised micelles.
Absorption:
- Move by simple diffusion from micelle to cell
- Bile absorbed in ileum
-Transported to ER, resynthesises to TAGs (maintains diffusion gradient)
- Secreted from goggle as chylomicrons
- Exocytosed at basolateral into lacteals
- Fat soluble = no need for transporter
Protein
- Only 40-90g per day
- Supply AAs
- AAs + very small peptides = absorbed
Gastric Digestion:
- Minor amount
- Hydrolysis in acidic pH
- Pepsin (chief cells) only active in low pH, cleaves polypeptides at neutral AAs
Intestinal Luminal Digestion:
- Major site
- Releases free AAs + short peps
- Enzymes (P bonds): trypsin, chymotrypsin, elastase
- Enzymes (C-terminus): Carboxypeptidase
Contact Digestion:
- Membrane digestion
- Large number of brush border peptidases
- Expressed close proximity to transporters
Protein Absorption:
- Na+ Dependent: Apical Na+/Amino cotransport, Basolateral amino specific transport
- H+ Dependent: The dude + K+ + amino acid specific basolateral, PEPT1/H+ cotransport apical. Cytosolic peptidases cleave into AAs.
Vitamin Absorption
Water Soluble
Vit C:
- Ionised in intestinal lumen pH
- Na+ coupled co transport
- SVCT1 and 2 in apical membrane, Vit C specific in basolateral.
Vit B12:
- Binds to IF in stomach
- Absorbed in ileum (endocytosis)
- Binds to transcoalabamin II for transport through cell
- Exocytosed across basolateral membrane
Fat Soluble
- Absorbed via simple diffusion.
- Dependent on micelle formation
- Stored in body fat reserves
Deficiencies:
- Defective bile salt secretions: Vit A & D deficiencies