Digestion and Weight Regulation Flashcards
What are the main features of the anatomical layers of the gut?
- Epithelium: specialised for absorption (fast turnover)
- Mucosa: protects gut as immune cells contained
- Submucosa: contains secretory glands (E.g. Brunner’s glands in duodenum) and submucosal plexus (nervous control)
- Muscularis externa: muscular wall (circular and longitudinal) and myenteric plexus to control them
- Serosa: suspends gut in mesentery (prevents tangling)
What are the inputs for the enteric nervous system?
Input from CNS – coordinates to outside world
Parasympathetic promotes mobility:
- Vagus nerve (long preganglionic neuron)
- ACh released on enteric nerves
Sympathetic:
- Preganglionic release of ACh in prevertebral ganglion
- Postganglionic releases NA on myenteric/submucosal plexus
- NA inhibits gut digestion
What afferents from the enteric nervous system exist?
Intrinsic primary afferent neuron (IPAN):
- Intrinsic reflexes
- Cell body in submucosal plexus
Intrinsic fugal afferent neuron (IFAN):
- Long distance reflexes
- Cell body in mucosal plexus synapsing on preganglionic SNS synapse.
- Short circuits the ENS in long-distance reflexes (e.g. for pain) reducing number of synapses and time.
General visceral afferent = ‘normal’ sensory fibre (innervates gut epithelium to CNS)
- Vagus nerve: can allow for vasovagal reflexes (entirely carried in Vagus nerve)
- Important in nociception (can lead to referred pain)
Describe the structure of smooth muscle and how it is adapted for a large SA:
Cytoplasmic dense bodies anchor cells with actin/myosin running at different directions:
- Relies on Ca2+ coming in across membrane (through VG channels) NOT internal stores.
- Therefore high Ca2+ accessibility required
Large SA (for high Ca2+ diffusion rates)
- Caveolae indentations to increase SA
- Calcium induced calcium release (from SR)Electrical and physical coupling (similar idea to heart)
- Smaller than skeletal muscle cells
Electrical and physical coupling(similar idea to heart)
- Forming functional syncytium
- Gap junctions between muscle fibres
How does smooth muscle contract? How does this compare to skeletal muscle contraction?
Contraction mechanisms:
- Ca2+ bind calmodulin
- Activates MLCK which phosphorylates myosin causing contraction
- Contraction stopped by MLCP (phosphatase)
- Peristalsis = waves of circular and longitudinal contraction/relaxation to move food along gut.
Differences from skeletal muscle:
- No troponin involved
- Enzymes used instead (slower)
- Slower contraction but more contraction
Describe peristalsis and the local mechanisms which control it:
Waves of circular and longitudinal contraction/relaxation to move food along gut.
Local control mechanisms:
- Peristaltic reflex (Starling): stretch due to bolus causes relaxation and contraction
- Local stretch causes 5-HT release by enterochromaffin cells (in mucosa)
- IPANs stimulated in myenteric plexus
Oral side neurons release ACh = contraction
Anal side neurons release NO = relaxation
- Serotonin must be removed to prevent +ve feedback of this process
What are slow waves? How do they cause movement?
Slow waves = fluctuating membrane potentials (from -50 to -20mv) over several seconds
- Due to interstitial cells of Cajal (ICCs) (generate slow waves and coordinate other cells through gap junctions)
- Innervated by ENS to cause modulation
- Spikes (Ca2+ based action potentials through L-type VG Ca2+ channels) can be overlayed on top to cause a coordinated contraction
- Isolated gut cells do not show this)
How are slow waves modulates by the ENS?
Modulated by ENS:
- Suppressed by NA or excited by ACh
- Excitatory transmitters ➡ increase Na+/Ca2+ ➡ depolarise cells (stronger and longer contraction)
- Controls amplitude of contraction without controlling frequency to stop peristalsis
- Inhibitory transmitter ➡ increase K+ ➡ hyperpolarise cells
Which peptide hormones control acid secretion and protection?
- Secretin: produced by S cell (duodenum) to protect from acid: stimulates bicarbonate rich solution from pancreas and constriction of pyloric sphincter
- Gastrin: promotes acid release
Which hormones are responsible for appetite regulation?
- Ghrelin: promotes appetite
- Incretins (GIP/GLP-1): promote insulin release (suppress appetite)
Which hormones are involved in movement of the gut and Gaul bladder?
Neurocrine:
- ACh (excitatory)
- NA (inhibitory)
- NO and VIP
Paracrine: do not travel in blood
- 5-HT and HA
Endocrine:
- Motilin: initiates migrating myoelectric complex
- CCK: produced by I cells of small intestine stimulates Gaul bladder contraction - relaxation of sphincter of Oddi (leads to removal of fatty products).
What is potentiation? Give an example of occurance in the digestive system:
When response of cell to a combination for messengers exceed sum of response to same messengers delivered individually (synergism)
- Often due to activation of two different intracellular pathways
- E.g. SNS (raised cAMP) and PNS (raised Ca2+) stimulated together = large increase in amylase
What are the functions of saliva?
- Lubrication
- Defence (lysozyme, lactoferrin, IgA, proline-rich proteins to reduce tannin toxicity)
- Buffering (HCO3- combats acid)
- Digestion (amylase)
How is saliva produced and modified?
Primary secretion:
- Na+ actively secreted; water follows into acinus
Secretion modified through intercalated duct:
- Active movement and ion composition
- Na+ replaced with K+
- Cl- replaced with HCO3-
Shown by saliva composition against flow rate experimentation – also showed that process is active (not ultrafiltration like kidney)
What are the mechanisms behind PNS and SNS control of salivary secretion? How does this exhibit synergism?
Anticipatory response (Pavlov’s dogs)
Parasympathetic activation:
- Produce ACh and VIP
- ACh binds M1/2 receptors to increase Ca2+ and therefore secretory volume
- VIP promotes vasodilatation and myoepithelial contraction
Sympathetic activation:
- NA binds β1 receptors increasing cAMP levels and exocytosis
- NA produced promoting myoepithelial contraction
- Secretory enzyme content increased
How is motility of the oesophagus achieved? Why might it fail? How can movement be detected?
Top 2/3rds:
- Due to skeletal muscle
- Requires external neuronal stimulation to sequentially stimulate muscle regions
Bottom 2/3rds
- Smooth muscle
Ends:
- Upper and lower oesophageal sphincter
- Lower sphincter requires extrinsic innervation from Vagus nerve
Movement can be seen by internal pressure changes within oesophagus.
Failure = achalasia (sphincter contracted and not responsive to enteric nervous system)
- E.g. caused by trypanosoma cruzi in Chagas’ disease
How is emesis stimulated; prepared for and consequences?
Stimulated by:
- Stretch of GI tract to vomiting centre in medulla (via vagus nerve)
- Emetic drugs
Prepared for by:
- Increased salivation
- Reverse peristalsis and lowering intrathoracic pressure/raising abdominal pressure
- Sphincter opening
Consequences:
- Damage (tp oesophagus and teeth)
- Ion imbalances (metabolic alkalosis; hypokalaemia)
- Hypovolaemia
How does the stomach move?
Retropulsion due to slow waves:
- Muscle contraction towards pylorus and forcing antrum through (grinding effect)
- Pylorus diameter controls emptying rate
Migrating myoelectric complex:
- To empty stomach
- Controlled by motilin
Enterogastric reflex: Keeps stomach full:
- Reduce stomach motility/tighten sphincter
- Stimulated by CCK (fat and acid in duodenum)
- Stimulated by duodenal stretch
- E.g. Ileal brake (food products detected in ileum
How can the size of the stomach sphincter be experimentally measured?
- Use of radiolabelled glucose solution and radio-opaque plastic spheres
- Measure time between intake and stomach emptying.
How is the anus controlled? Give an example of when this control goes wrong:
Skeletal muscle which responds to stretch of the colon (internal anal sphincter):
- Activation of autonomic fibres from the spinal cord
- Activation of intrinsic nerves to release NO/VIP
- Relaxation
- External sphincter: spontaneously contracts on stretch (relaxed voluntarily to defecate)
- Defecation increased by valvasa manoeuvre (increasing pressure in abdominal library)
Hirschsprung’s disease results in missing communication of myenteric neurons to sphincter = problems passing stool
What are the secretory glands of the stomach? What do they produce?
Top of stomach: Cardiac glands = Mucus
- Mucus traps HCO3- as protective layer
Majority: Oxyntic glands = acid/enzymes
- Zymogens (inactive enzymes E.g. pepsinogens; chymosin (=rennin) for milk digestion)
- Intrinsic factor: binds to B12 to protect it (allows ileal endocytosis)
Bottom 1/3: Pyloric glands = mucus and gastrin
- Gastric acid: delays stomach emptying, solubilises and improves ion absorption (Fe, Ca) and kills microbes
Parietal cells = gastric acid
How might stomach acid composition state change in a fasted/fed state?
Fasted state:
- Mainly NaCl
- Lower acid concentration
- Protects stomach and reduces metabolic cost of gastric juice production
How is stomach acid secretion controlled?
Promoting secretion:
- Gastrin (G cells): promotes parietal and ECL cell action by raising Ca2+
- HA (from enterochromaffin-like cells): binds H2 to increases cAMP levels in parietal cells
- ACh: increases Ca2+ levels in parietal cells
Inhibiting secretion:
- Secretin
- Somatostatin (produced by D cells): reduces cAMP levels in parietal cells
- Prostaglandin
