Digestive Physiology Flashcards
what is digestion?
the physiological process whereby the nutritive part of the food consumed is, in the stomach and intestines, rendered fit to be assimilated by the system
what does the basic histological structure of the gut tube consist of?
mucosa, submucosa, muscularis externa, serosa, simple squamous epithelium
what does the mucosa consist of?
consists of the epithelium, lamina propria and muscularis mucosae
what is the innermost layer of the gut tube?
mucosa
what is the lamina propria?
loose connective tissue containing glands, lymph nodules and capillaries
what is the muscularis mucosae?
thin layer of smooth muscle which throws the mucosa into folds
what are villi?
finger-like projections in the SI which increase the internal SA
what does the submucosa contain?
blood vessels, nerves, glands, the submucosal plexus (Meissner’s plexus)
what are the layers of the muscularis externa?
inner circular and outer longitudinal smooth muscle, myenteric plexus (Auerbach’s plexus) located between the 2 layers
what is the serosa?
outermost layer of connective tissues, covered by simple squamous epithelium
what is the splanchnic circulation?
the blood supply to the stomach, intestines, liver, spleen and pancreas
how much of the splanchnic circulation passes via the intestines to the liver in the hepatic portal vein?
around 75%
how much of the splanchnic circulation passes directly to the liver via the hepatic artery?
around 25%
what is functional hyperaemia?
after a meal splanchnic blood flow increases up to around 2500mlmin-1
what is the resting value of splanchnic blood flow?
around 1200mlmin-1
what is responsible for functional hyperaemia?
metabolites which increase during digestive activity, certain gut hormones and absorbed substances
what effect can maximal sympathetic vasoconstriction have on splanchnic blood flow?
can reduce it to as little as 300mlmin-1
how much of the blood volume do the great veins of the gut hold at rest?
about 20%
which direction do arterial and venous blood supply to each SI villus travel in?
arterial supply ascends from the base, venous supply descends towards the base- counter-current arrangement
how much blood can venoconstriction add into general circulation from the mesenteric veins and from the liver?
about 400ml from the mesenteric veins plus around another 200ml from the liver to the general circulation
where do the products of fat digestion go in the intestinal villi?
enter the lacteals within the villi
how are the central lacteals of the intestinal villi emptied into the lymphatic system?
irregular contractions of smooth muscle within the lamina propria of the villus stimulated by increased interstitial fluid pressure, help empty the central lacteals by squeezing. valves in submucosal lymph vessels prevent backflow
what is the gut epithelium comprised of?
single layer of columnar epithelial cells
why do the gut epithelium cells have a high turnover rate?
vital in preventing microbial invasion and very vulnerable to mechanical damage
how often is the entire gut epithelium estimated to be replaced?
every 2-6 days
how are the cells of the SI epithelium replaced at such a high rate?
old epithelial cells shed from the villus tips, replaced by new ones moving up the sides of the villus in conveyor-belt like fashion. new cells arise from stem cell population in the crypts of Lieberkuhn, before old cells shed new tight junctions formed under them between their neighbours to ensure barrier function of gut isn’t compromised
what are the crypts of Lieberkuhn?
blind-ending tubules projecting into the gut lining between villi
what make up the ENS?
the submucosal and the myenteric plexi which extend from the middle of the oesophagus to the colon
main function of the submucosal plexus?
co-ordinates motility
what are the inputs for the ENS?
sensory cells in gut wall, ANS fibres synapsing on ENS fibres
how does the ANS innervate the gastrointestinal tract?
forms synapses with ENS fibres
where is ANS input to the ENS particularly important?
proximal gut and rectum, ENS and hormones more important in between
where do sympathetic nerve fibres synapse outside the CNS
only synapse once, either in one of the paravertebral ganglia of the sympathetic chain or in a separate prevertebral ganglion within the abdominal cavity
what sort of fibres are postganglionic sympathetic nerve fibres normally?
noradrenergic
effect of sympathetic stimulation on gut motility and secretion, and on sphincter contraction?
inhibitory to gut motility and secretion, stimulates sphincter contraction
what carries parasympathetic supply to the gut?
the vagus
what sort of fibres are the postganglionic parasympathetic nerve fibres predominantly, where is the synapse between the pre and post-ganglionic fibres usually?
fibres are cholinergic, synapse between pre- and post-ganglionic fibres is within ENS
what is the effect of parasympathetic stimulation on gut motility, secretion and sphincters?
stimulates gut motility and secretion, may relax sphincters via inhibitory post-ganglionic fibres which often release VIP
what do the pelvic nerves supply?
distal colon, rectum and anus
are the pelvic nerves sympathetic or parasympathetic?
sympathetic
where are the sensory fibres of the gut located?
IPANs are entirely within the ENS, general visceral afferent fibres have cell bodies in PNS, IFANs- sensory fibres with cell bodies in ENS that have axons that synapse in the sympathetic chain
what are IPANs?
intrinsic primary afferent neurons- sensory fibres located entirely within the enteric nervous system. form the afferent limbs of local reflexes including those responsible for peristalsis, mixing and secretion
what are the general visceral afferent fibres?
sensory fibres of gut with cell bodies in dorsal root ganglia or homologous ganglion of the vagus. axons transmit signals from gut to spinal cord/brainstem and are involved in certain stomach reflexes, pain, defecation reflexes
what % of fibres in sympathetic nerves to the gut and what % of vagal fibres to the gut are general visceral afferent fibres?
50% in sympathetic nerves, 75% of vagal fibres
what are vagovagal reflexes?
reflexes in which both afferent and efferent arms are carried by the vagus nerve
what are IFANs?
intestinofugal afferent neurons, sensory fibres of gut with cell bodies in ENS that send axons with the sympathetic nerves to synapse in the prevertebral sympathetic ganglia. fibres often form afferent limbs of long-range inhibitory reflexes used to coordinate activity of different parts of gut
how do the long range reflexes of the GI tract work?
GI hormones contribute both directly and by stimulating vagal afferent fibres to elicit a neural response. the long range reflexes usually involves a synapse in the prevertebral ganglia. responsible for overall coordination of activities of GI tract
what is the ileal brake mechanism?
example of a long range reflex of the GI tract. refers to the effect of nutrients which have reached the ileum without being absorbed reducing the motility and secretion of more proximal parts of the digestive tract. may involve peptide hormones PYY and LGP-1 as well as nerve fibres
what is the gastrocolic reflex?
example of a long range reflex of the GI tract. where food entering the stomach promotes the motility of the colon which may result in urge to defecate
how can voluntary control be exerted over swallowing and defecation?
striated muscle is present at each end of the digestive tract
how is smooth muscle in the GI sphincters controlled?
tonically contracted for durations of minutes to hours. relaxes when required
typical contraction of smooth muscle in walls of stomach and intestines?
phasic contraction- slow and rhythmic. wave of depolarisation spreads through gap junctions, cells are also mechanically coupled allowing coordinated contraction. smooth muscle in which cells electrically coupled= single unit smooth muscle
excitation-contraction coupling in smooth muscle?
calcium inside the cell bind to calmodulin- complex activates MLCK which phosphorylates a regulatory light chain on myosin allowing it to bind with actin and undergo cross-bridge cycle. when calcium level falls the myosin is dephosphorylated by MLC phosphatase which prevents further cycling
what is peristalsis?
gut motility patterns which propel food in the anal direction
what is the peristaltic reflex?
type of peristalsis which occurs when stretching of gut wall elicits contraction of the longitudinal and circular muscle behind a bolus (mediated by ACh) and relaxation of the muscle in front of the bolus (mediated by NO) propelling the food onwards
does the peristaltic reflex require extrinsic innervation?
no, mediated entirely within the ENS
how is food detected in the peristaltic reflex?
may be via mechanical stretch receptors in the myenteric plexus or mechanical or chemical stimuli to the mucosa promoting serotonin (5-HT) release from enterochromaffin cells which stimulates local sensory neurons
what controls peristalsis in the striated muscle portion of the oesophagus?
somatic motor neurons causing sequential contractions of the striated muscle
what causes peristalsis in the antrum of the stomach and in the MMC?
slow wave activity
range of the resting MPs of smooth muscle cells of the gut?
from around -70 to -40mV
amplitude of slow waves of electrical activity in the smooth muscle of the gut?
between 10-50mV
what is the tone of the smooth muscle of the gut?
basal level of tension between slow waves of depolarisation
what are the pacemakers in the gut?
the ICCs (interstitial cells of Cajal)
what are the ICCs?
specialised smooth muscle cells containing a few contractile elements located mainly between the longitudinal and circular muscle layers. innervated by ENS, acts as pacemakers for gut smooth muscle
how do the ICCs act as pacemakers?
gap junctions with each other and nearby smooth muscle cells in both circular and longitudinal layers: slow waves propagated within the ICC network and spread from there to the smooth muscle cells
what does depolarisation of smooth muscle cells by slow waves originating in the ICCs do?
results in opening of L-type VGCaCs in their plasma membranes so calcium enters cell- if enough enters then the muscle will contract, APs may be generated if it exceeds a certain threshold- spike potential
which are longer, spike potentials in smooth muscle or APs in a nerve?
spike potential is up to 20ms longer
how do excitatory substances (e.g.. ACh) increase amplitude of slow waves in gut smooth muscle?
opening cation channels which contribute to the depolarisation- more depolarisation means more spikes, more calcium entering cell, stronger contraction
how do inhibitory substances (eg. NA) decrease amplitude of slow waves in gut smooth muscle?
opening of hyperpolarising K+ channels resulting in weaker contraction/no contraction if amplitude under contraction threshold
what causes tonic contraction of sphincter muscle?
can be caused by continuous sequence of APs, partial depolarisation of the smooth muscle cell membrane without APs or other mechanisms resulting in sustained levels of intracellular Ca2+
what is segmentation?
where different regions of the circular muscle of the gut contract to aid mixing
what drives and modulates segmental contraction in the gut?
driven by slow waves initiated in the ICCs, modulated by nerves and hormones (e.g. gastrin)- excitatory parasympathetic stimulation and inhibitory sympathetic stimulation
what is neurocrine transmission?
when nerve terminals release a transmitter onto a target cell or into blood
what receptors does ACh act on in the gut? effect of this?
muscarinic receptors. excites smooth muscle and stimulates secretion of many glands
what do NO and vasoactive internal peptide (VIP) do in the gut?
typically relax smooth muscle, VIP stimulates secretion
what does NA do in the gut?
released by sympathetic neurons, typically inhibitory but promotes contraction of sphincters and vascular smooth muscle
what is paracrine transmission?
involves a locally-produced substance diffusing through the ECF to work on neighbouring cells of a different cell type
what is endocrine transmission?
involves transmitters travelling via the blood
what sort of hormones are all GI hormones?
peptides secreted by the enteroendocrine cells which are scattered throughout the gut epithelium
role of the apical membrane on most enteroendocrine cells?
has receptors that detect luminal conditions and stimulate hormone release in response
what cells secrete secretin and why?
S cells of the duodenum in response to the presence of acid
roles of secretin?
stimulates pancreatic growth HCO3- and water secretion, inhibits gastric acid secretion and motility, promotes constriction of the pyloric sphincter
what cells release gastrin and why?
G cells of the gastric antrum and duodenum in response to nervous stimulation + presence of peptides and amino acids
roles of gastrin?
stimulates gastric acid secretion by parietal cells, promotes growth of the oxyntic mucosa
what cells release cholecystokinin (CCK)?
I cells in the duodenum and jejunum in response to long chain FFAs and mono-glycerides
roles of cholecystokinin?
stimulates gall-bladder contraction, pancreatic secretion and growth, inhibits gastric emptying and appetite
what are the incretins? what is their function?
GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide 1). augment insulin release from pancreas following a meal
what secretes GIP? what secretes GLP-1?
K cells in the upper SI secrete GIP, L cells in Si and Li secrete GLP-1
role of GLP-1 agonists as a drug?
used to treat type II diabetes
what secretes motilin, what controls this release?
M cells in upper SI, under neural control, cyclical release during fasting
what is the only know action of motilin?
initiates migrating myoelectric complex
what secretes grehlin? when?
endocrine cells of the stomach in response to fasting
role of grehlin?
works on hypothalamus to stimulate appetite and promotes GH release from pituitary gland
what is potentiation?
when the response of a cell with receptors for more than 1 type of messenger/different types of receptor for the same messenger exceeds the sum of the responses to each messenger delivered individually causing activation of different pathways with same end point
what is the difference between the secretion produced by the parotid vs the sublingual and submandibular glands
parotid only produces serous secretion, sublingual and submandibular produce mixed mucous/serous secretion
major functions of saliva?
lubrication, defence, buffering, digestion
how does saliva provide lubrication?
glycoproteins called mucins produced by mucus secreting glands.
how does saliva provide defence?
contains isozyme, lactoferrin and antibodies (IgA). proline rich proteins bind to and neutralise the effects of plant tannins in humans + herbivores
how does saliva provide buffering?
HCO3- ions raise pH of saliva- from slightly acidic at basal secretion level to around 8 during active secretion
how does saliva provide digestion?
contains amylase (not in cats, dogs or horses) which breaks down starch to oligosaccharides. inhibited by low pH in stomach, when protected inside bolus of food activity can continue for up to 1/2 an hour, has time to digest up to 75% of the starch in a meal
what produce the primary secretion of salivary glands? what is its composition?
the acinar cells. it is isotonic to plasma and high in NaCl
how is water drawn into the acinar lumen?
osmosis due to the accumulation of NaCl in the lumen
what do the acinar cells secrete?
the primary secretion, plus salivary enzymes and other proteins by exocytosis
what helps to empty saliva into ducts?
contraction of myoepithelial cells
what happens to the primary secretion as it proceeds through the ducts?
modified by the duct cells, becomes more hypotonic, ion exchange of Na+ for K+ and HCO3-
what does aldosterone promote in the salivary ducts?
ion exchange
what mediates almost the entire control of salivation?
the ANS
what is the cephalic phase of digestion?
anticipatory response to prospect of food which promotes salivation
role of parasympathetic output to the salivary glands?
ACh and VIP promote vasodilatation and increase blood supply, metabolism and growth. also causes contraction of the myoepithelial cells and opens more of the acinar cell channels increasing volume of saliva secreted
role of sympathetic output to the salivary glands?
promote myoepithelial cell contraction and via cAMP promotes exocytosis increasing protein content
what is the overlap between the sympathetic and parasympathetic pathways in the acinar cells of the salivary glands?
crossover between the cAMP (sympathetic) and Ca2+ (parasympathetic) pathways
what initiates swallowing?
when food is pushed towards the back of the mouth by the tongue, touch receptors in the pharynx initiate the swallowing (deglutition) reflex, coordinated in swallowing centre in medulla and lower pons
what is deglutition apnoea?
respiratory system of the medulla is directly inhibited by the swallowing centre for the brief time it takes to swallow
muscles of upper, middle and lower 1/3 of human oesophagus?
upper 1/3 is striated, middle is mix of striated and smooth, lower 1/3 is entirely smooth
peristalsis in the oesophagus?
primary peristaltic wave starts just below UOS, sweeps bolus downwards at 3-5cm/sec. if doesn’t manage to be moved all the way to stomach secondary peristaltic wave initiated by persistent distension of oesophagus- initiated partly by local reflex, partly through vagovagal reflex
what is the lower oesophageal sphincter?
region of specialised circular smooth muscles at the bottom of oesophagus, controlled by ENS fibres which receive input from ANS. tonically contracted, feed-forward vagal reflex means relaxes before food has even arrived- relaxation believed to be promoted by NO
importance of the LOS?
preventing the acid contents of the stomach from entering the oesophagus (gastro-oesophageal reflux)
how much mucus does the oesophagus secrete, what is its function?
only small amounts, used to lubricate food when swallowing and protect mucosa against acid reflux
where is emesis (vomiting) coordinated?
vomiting centre in the medulla oblongata
what is the chemoreceptor trigger zone for vomiting?
receptors on the floor of the 4th ventricle of the brain, stimulation of which leads to vomiting. lies outside blood brain barrier (so can be stimulated by blood-borne drugs)
where can emetic drugs target?
can either travel in blood to chemoreceptor trigger zone for vomiting in the brain or work in GI tract sending signals to brain via vagus
what does vomiting entail?
increased salivation, retroperistalsis (from middle of SI) sweeping contents up digestive tract into stomach through relaxed pyloric sphincter, lowering of intrathoracic pressure + increase in abdominal pressure as abdominal muscles contract, stomach contents propelled into oesophagus. lower oesophageal sphincter relaxes. if UOS stays contracted person retches, if UOS relaxes stomach contents are expelled
general functions of the stomach?
acts as reservoir for food to be eaten quickly, releasing contents at controlled rate. facilitates digestion including initiating protein digestion, destroys some ingested microbes with acid, helps regulate appetite through feedback on brain, helps regulate activity of later parts of gut through feed-forward mechanisms
what causes stomach fundus and body relaxation when oesophagus or stomach stretches?
vagovagal reflex
which region of the stomach performs more forceful contractions?
the antrum- has thicker muscular walls
what does the antrum lead into?
the pylorus
what forms the pyloric sphincter?
circular muscles of the pylorus- it isn’t anatomically discrete from pylorus
what limits rate of stomach opening?
narrow opening of pyloric sphincter
describe gastric motility
ICCs in pacemaker zone of stomach body generate slow waves (around 3 per min), these propagate down towards pylorus, stop there as pyloric sphincter region lacks ICCs. towards antrum APs may be superimposed of plateaus of gastric slow waves
what increases chance of gastric APs and therefor contractions in the fed state?
substances including ACh and gastrin increasing duration of the plateau phase of gastric slow waves
what is retropulsion?
following meal contractions sweep down stomach body and antrum becoming increasingly powerful, as wave of contraction approaches pylorus the pyloric sphincter contracts to prevent passage of ingesta forcing stomach contents back towards middle of stomach. results in antral mill
what is the antral mill?
movement of stomach contents towards pyloric sphincter and then back to middle of stomach (retropulsion), functions to break up larger particles
what is chyme, how is it formed?
mix of food and gastric secretions formed in stomach during antral mill movement of stomach contents
how are contents allowed to pass into the duodenum out of the stomach?
pylorus relaxes between stomach contractions allowing contents out- only liquid and particles under 2mm diameter
control of gastric emptying?
tone of pyloric sphincter controlled by ENS, ANS and circulating hormones. relaxation promoted by inhibitory fibres in ENS releasing NO. MMC promotes empting of residual particles, neural and hormonal reflexes involved in slowing emptying of stomach contents by inhibiting gastric motility/tightening the pyloric sphincter
what causes slowing of gastric emptying as a response?
excess acid (duodenal pH below 4), fat digestion products in duodenum, peptides and amino acids in duodenum, duodenal stretch, the ileal brake
what are the glands of the stomach mucosa?
cardiac glands near entrance of oesophagus, oxyntic glands in fundus and body, pyloric glands in antrum
what do the cardiac glands secrete?
mainly mucus
what do the oxyntic glands secrete?
oxyntic/parietal cells secrete HCl + IF, chief/peptic cells secrete pepsinogens + prochymosin, mucus secreting cells line the necks
what do the pyloric glands secrete?
mucus from mucus secreting cells, G cells which secrete gastrin
what promotes secretion of pepsinogens from chief cells?
vagal ACh and a cholinergic reflex in response to acidity
effect of acidity on pepsinogens?
catalyses cleavage of active pepsinogens to form pepsins which digest proteins + peptides, pepsins can then also cleave pepsinogens. pepsins require low pH to work properly
effect of acidity on prochymosin?
catalyses its cleavage to form active chymosin (rennin)
effect of chymosin in neonatal mammals?
curdles milk converting the soluble protein caseinogen into insoluble casein, allows the milk protein to remain in stomach long enough to be acted on by pepsins
what is responsible for milk curdling in human neonates?
pepsins- the prochymosin gene is inactive in human neonates unlike other mammal neonates
what protects vitamin B12 from stomach acidity?
binds to haptocorrin, secreted in saliva
what does B12 bind to in the SI once released by haptocorrin?
binds to intrinsic factor (glycoprotein secreted by stomach)
what does the B12-IF complex do?
resists digestion by proteases, is taken up into the epithelial cells of the ileum by receptor mediated endocytosis
what is the only gastric function essential to human life?
secretion of IF by the parietal cells
functions of gastric acid?
delays gastric emptying, solubilises so improves absorption of Ca2+ and Fe, helps to release vitamin B12 from food, activates pepsinogens, destroys ingested microbes
what does gastric juice contain more of between meals?
NaCl
what happens when the parietal cells are stimulated?
tubules and vesicles with membranes containing transport proteins fuse with the luminal membrane of the parietal cell, at maximal stimulation gastric juice becomes largely isotonic solution of HCl
why are the pumps of the gastric glands working against a large concentration gradient during maximum secretion?
intracellular pH is 7 and pH within gastric gland can be as low as 0.8
how are protons generated and secreted by parietal cells?
generated from the intracellular reaction of CO2 with water under the influence of carbonic anhydrase (CA), secreted by the H+/K+-ATPAse pumps (proton pumps) on luminal membrane of parietal cells
what else is formed in the reaction to generate H+ in parietal cells, how is this secreted?
H2O + CO2 -> HCO3- + H+, exchanged into ECF for Cl- by secondary active transporter on the basolateral membrane using energy from the electrochemical gradient for HCO3-
how is Cl- secreted by the parietal cells?
enters from basolateral side in exchange for HCO3-, exits down electrochemical gradient through channels in luminal membrane
effect on blood plasma as acid is secreted by gastric glands?
CO2 removed from plasma and bicarbonate added, gastric venous blood becomes more alkaline
controllers of acid secretion by parietal cells?
1 endocrine transmitter (gastrin), 1 paracrine transmitter (histamine), and 1 neurocrine transmitter (ACh)
how does gastrin promote acid secretion by parietal cells?
released by G cells in antrum and duodenum, travels in blood to parietal cells. promotes histamine production and release from ECL cells, and increases free Ca2+ in parietal cell
how is gastrin release stimulated?
local stretch reflexes via ACh, vagal stimulation via gastrin releasing peptide (GRP), peptides, a.a.s and Ca2+ in the stomach lumen
how does histamine promotes acid secretion by parietal cells?
released from enterochromaffin-like cells in the gastric glands (so is paracrine transmitter), is agonist of HCl secretion, acts on H2 receptors to increase cAMP
how does ACh promote acid secretion by parietal cells?
released from nerve terminals, promotes release of acid, histamine and gastrin, inhibits somatostatin release, increases free Ca2+ in parietal cell
what is required for maximum secretion of HCl?
activation of Ca2+ and cAMP pathways
what mediates inhibition of acid secretion from parietal cells?
somatostatin, secretin and prostaglandins
how does somatostatin inhibit parietal cell acid secretion?
paracrine transmitter released from D cells in response to luminal acidity, inhibits parietal cells
how does secretin inhibit parietal cell acid secretion?
released from S cells in response to acid in duodenum, inhibits acid secretion indirectly by stimulating vagal afferent fibres. reflexes elicited reduce gastrin release from G cells
how do prostaglandins inhibit parietal cell acid secretion?
paracrine transmitters which promote bicarbonate and mucus production
acid secretion in the cephalic phase of digestion?
acid secretion increases but negative feedback through somatostatin release and neural reflexes limits any pH change. accounts for around 30% of total secretion
acid secretion in the gastric phase of digestion?
protons buffered by proteins in food, luminal pH rises to around 6, releases secretory mechanisms from inhibition so dramatic rise in acid secretion, compounded by stretch of stomach wall causing vagovagal and local reflexes to increase gastrin and acid release, and peptides and amino acids stimulating G cells to increase gastrin secretion
acid secretion in the intestinal phase of digestion (when chyme enters duodenum)?
duodenal stretch initially triggers vagovagal relfexes increasing acid secretion by stomach, and peptides and amino acids cause gastrin release from duodenal G cells- as duodenal contents become increasingly acidic acid secretion by the stomach is decreased
how is the stomach mucosa protected from acid and ulcer formation?
by secretion of mucus and bicarbonate by the mucous cells forming the epithelial lining of the stomach and in the necks of the gastric glands, which forms alkaline lining the gastric mucosal barrier which helps maintain the luminal surface of the stomach at pH 6-7
how are the mucous cells that form the gastric mucosal barrier maintained?
epithelial mucous cells continually lost from stomach surface and replaced by mucous cells from necks of the gastric glands which migrate upwards and over the surface. neck mucous cells replaced as stem cell deeper within the glands divide and differentiate
what causes gastric ulcers?
if the gastric mucosal barrier is compromised the surface of the stomach can be attacked by acid and pepsins causing a gastric ulcer
how can gastric ulcers be treated?
with drugs that suppress acid secretion, including H2 receptor antagonists and H+/K+-ATPase proton pump inhibitors. if caused by Helicobacter pylori requires antibiotic treatment as well
predisposing factors for ulcer formation?
overuse of NSAID drugs such as aspirin, presence of gram-negative bacterium Helicobacter pylori which inflames the stomach wall
what does the pancreas secrete?
produces an endocrine secretion (insulin and glucagon) and an exocrine secretion which enters the duodenum and is HCO3- rich, as well as having enzymes like amylase, lipases, proteases, ribonucleases + deoxyribonucleases
how do pancreatic acinar cells secrete enzymes?
exocytosis, proteases secreted as inactive zymogens
how is pancreatic secretory trypsin inhibitor (PSTI) secreted?
in zymogen granules with trypsinogen
role of pancreatic secretory trypsin inhibitor?
helps protect acinar cells from inappropriate trypsin activation
what cells secrete the exocrine pancreatic secretion?
acinar cells secrete small amount of NaCl rich solution into acinus lumen, pancreatic duct cells secrete bulk of aqueous component of pancreatic juice in the form of HCO3- rich solution
how is pancreatic secretion stimulated?
parasympathetic nerves, enteric neurons passing from stomach and duodenum. in cephalic phase secretion stimulated by feedforward control, in gastric phase occurs in response to vagovagal and local neural reflexes, in intestinal phase secretin stimulates HCO3- and water secretion from pancreatic duct cells to increase secretion
main stimulus for cholecystokinin release?
fat digestion products in the duodenum
effect of CCK on pancreatic exocrine secretion?
stimulates enzyme secretion from acinar cells, potentiates effects of secretin on duct cells
effects of ACh, CCK, secretin and VIP on pancreatic cells?
ACh and CCK increase intracellular [Ca2+] whereas secretin and VIP increase intracellular [cAMP]- both augment secretion
effect on cAMP on acinar and duct cells and therefore secretion?
opens the luminal chloride channels (in duct cells this is the cystic fibrosis transmembrane conductance regulator) increasing secretion
what does the most common form of cystic fibrosis result in?
impaired water and electrolyte secretion into the pancreatic duct system
effect of clogged pancreatic ducts?
leads to severe maldigestion and nutrient deficiency, combined with premature activation of proteolytic enzymes can cause pancreatic damage
what is secreted by the gut epithelium?
NaCl by the intestinal crypts of Lieberkuhn and other epithelial cells
effect of cholera toxin?
permanently high [cAMP] leading to excessive secretion of Cl- with Na+ and water following leading to potentially life-threatening diarrhoea
how much doe the mucosal folds of Kerckring increase the SI SA?
around 3x
how much do villi increase the SI SA?
10x
how much does the brush border formed by microvilli increase the SI SA?
20x
role of the crypts of Lieberkuhn between the villi?
secrete fluid and also contain the stem cells for the replacement of desquamated epithelial cells that are continuously lost from the gut
how often is the entire SI epithelium replaced?
every 3-6 days
how much fluid is secreted by the SI, pancreatic secretion and biliary secretions each day?
up to 2 litres from SI, matched by the other 2
what do salivary and pancreatic amylase do? what can’t they do?
cleave the internal α-1,4 bonds in starch. can’t cleave the α-1,6 branching links or the α-1,4 bonds next to them
result of amylase breakdown of starch?
smaller chains of glucose molecules (oligosaccharides) mostly 2 or 3 units long plus α-limit dextrins which contain the branch points
what completes carbohydrate digestion after action of amylase?
enzymes on brush border of duodenum and jejunum
what breaks down the α-1,4 bonds within glucose oligosaccharides?
glucoamylase
what breaks down the α-1,6 bonds within glucose oligosaccharides?
α-dextrinase
what digests lactose?
lactase
what digests sucrose?
sucrase
what digests trehalose?
trehalase
what transporter on the apical membranes of duodenal and jejunal epithelial cells takes up glucose and galactose?
SGLT1 (sodium-glucose transport protein 1)
what transporter on the apical membranes of duodenal and jejunal epithelial cells takes up fructose?
GLUT5 - facilitated diffusion transporter
what is export of glucose, galactose and fructose into the ECF from the duodenal and jejunal basolateral membrane via?
GluT2
how much of protein digestion do pepsins contribute? what in particular are they useful in digesting?
up to 15%, particularly useful in digesting collagen
what are more important than pepsins in protein digestion?
pancreatic proteases
what converts trypsinogen to active trypsin?
enteropeptidase on the brush border of the upper SI, trypsin itself, other pancreatic proteases (chymotrypsin, elastase), the carboxypeptidases
role of pancreatic proteases?
digest proteins to peptides to be digested further by brush border peptidases
where are brush border peptidases located?
apical membranes of epithelial cells in the upper SI
how are the products of brush border peptidases (di and tripeptides) taken up into cells?
facilitated diffusion and secondary active transport
what happens to di- and tripeptidases once within the intestinal cells?
further digested into amino acids which are released from the cells by facilitated diffusion or secondary active transport, some amino acids then used within the intestinal cells themselves
what reduces calcium and iron availability in the SI?
their binding to other dietary constituents (e.g. phytate anions) to yield insoluble salts
main mechanisms for calcium absorption in SI?
uptake both transcellularly and paracellularly, secreted into ECF by CA2+ pump and Na+/Ca2+ exchange pump
how is iron absorbed in the SI?
iron reductase on duodenal brush border reduces Fe3+ to Fe2+ which is taken up via the proton-Fe2+ cotransporter DMT1, Fe2+ may also be taken up as haem. excreted into ECF by ferroportin
how does iron travel in the blood (other than as part of haem)?
bound to the protein transferrin
what happens to iron efflux into the ECF from duodenal cells in the presence of peptide hormone hepcidin? how does the body use this?
efflux is reduced, excess iron trapped in cell bound to ferritin- when epithelial cell shed the iron is lost. body increases hepcidin production to fight infection as bacteria need iron to grow
where is sodium absorption greatest in the GI tract? why?
the SI, as movement down its electrochemical gradient into the SI cells is coupled to movement of monosaccharides via SGLT1 and some amino acids, as well as Na+/H+ antiporters
what extra sodium transporters are present in the colon that aren’t in the SI?
epithelial sodium channels (ENaC)
what provides the driving force for paracellular K+ uptake by the small intestine?
as water is absorbed potassium becomes concentrated
net potassium flux in the colon?
normally net secretion via apical potassium channels
chloride absorption in the digestive tract?
via paracellular pathway and via exchange with bicarbonate
how does water enter the digestive tract?
through the ingesta (2l/day) and through GI secretions (saliva, stomach, pancreas, bile, crypts) (7l/day)
how much of the normal 9l of water entering the digestive tract is absorbed by the SI, colon and lost in faeces? how much more can the gut take if necessary?
around 7.5 l in SI, around 1.4 in colon, so around 100ml lost in faeces. can take 2-3x more than this if necessary
what is the standing gradient model of water uptake across an epithelium?
Na+ pumped into intercellular clefts by Na+ pumps concentrated around edges of the clefts on the basolateral membranes. anions follow. a solute concentration gradient is set up- highest near the tight junctions, decreasing towards the open ends where it becomes equal to the concentration in the bulk phase. due to high solute concentration within intercellular clefts water enters from the adjacent cells and from lumen via leaky tight junctions. rise in pressure drives flow across basement membrane whereupon water and salts taken up and removed by capillaries
why is absorption in the SI isosmotic?
the SI epithelium is leaky
why is much less water absorbed in the colon than the SI?
against a large osmotic gradient as tight junctions between cells are tighter limiting back-diffusion of ions
how are the fat-soluble vitamins absorbed?
similarly to fat- transported mainly in lymph
fat soluble vitamins?
A, D3, E, K
how are the water-soluble vitamins absorbed?
in SI by diffusion or active transport
how is vitamin B12 absorbed and how does it travel in blood?
absorbed via receptor-mediated endocytosis in ileum, exported from cells into blood, travels in blood bound to protein transcobalamin II
size of liver lobules?
several mm long, up to 2mm diameter
what is between liver lobules?
portal triads comprising branch of hepatic portal vein, branch of hepatic artery, branch of the bile duct
what lines the sinusoids?
rows of hepatocytes
what are bile canaliculi?
tiny channels that drain bile produced by hepatocytes lining sinusoids outwards towards the branches of bile duct that lie between lobules (bile flows countercurrent to blood)
functions of the liver?
carbohydrate, protein and lipid metabolism (including cholesterol synthesis and excretion in bile directly/as bile acids), bile formation, vitamin + iron storage (A, D, E, K and B12), destruction and detoxification of hormones, drugs, toxins, filtration of blood (removal of effete erythrocytes + bacteria from gut), blood reservoir
how does the liver take up monosaccharides from the portal vein?
GluT2 facilitated diffusion
how much glycogen can accumulate in liver and muscle? how long can this provide for the body’s needs for?
up to 100g in liver, up to 400g in muscle cells. provides for body’s needs for up to 24 hours
what happens to excess glucose in liver that can’t be converted to glycogen?
converted to triglycerides, exported as lipoproteins, stored as fat in adipocytes
protein metabolism by liver?
extracellular proteins digested by macrophages, intracellular returned as amino acids to liver- which can interconvert amino acids, pyruvate and TCA cycle intermediates by transamination to synthesise non-essential amino acids. excess amino acids oxidised for energy directly or converted to glucose or ketone bodies. urea and glutamine produced and exported
what does bile contain?
bile acids (65% of bile dry mass), phospholipids (20%), cholesterol (4%), bile pigments (0.3%)
roles of bile?
promotion of fat absorption, excretion of waste, protection
how does bile promote fat absorption
bile acids are surfactants, normally conjugated with glycine or taurine to increase their solubility, found as salts of cations like Na+. primary bile acids made from cholesterol in liver, some are converted to secondary bile acids by gut bacteria
how does bile excrete waste
primary means of cholesterol excretion, also secreted excess heavy metals like copper and cadmium
how does bile offer protection?
contains IgA, mucus and tocopherol (antioxidant)
the role of the gall bladder
collection and concentration of bile before expulsion into digestive tract
where is the sphincter of Oddi, what does it do?
at entrance to duodenum. contracts between meals so bile diverted into gallbladder. relaxed by CCK during a meal emptying gallbladder bile into duodenum
role of CCK in gallbladder bile secretion?
during meal CCK relaxes sphincter of Oddi and contracts gall-bladder so bile empties into duodenum
how are bile acids taken up in the terminal ileum and colon. how much is lost in faeces?
epithelial cells in terminal ileum take up bile acids by secondary active transport, most of rest absorbed passively in colon, 5% lost
what happens to secondary bile acids in the hepatocytes?
some reconverted to primary bile acids. both secondary and primary then resecreted into bile canaliculi
what is bilirubin?
bile pigment, yellow-coloured breakdown product of haem made in spleen, bone marrow and liver
how does bilirubin travel around body?
travels in blood mainly bound to albumin, taken up by liver, rendered soluble by conjugation with glucuronic acid before excretion in the bile
what happens to bilirubin in the distal ileum and colon?
bacteria break it down to urobilinogen, some of this is reabsorbed into blood and either resecreted in bile or secreted in urine, rest lost in faeces
what happens to urobilinogen in urine and in the gut?
in urine oxidised to yellow-coloured urobin, in gut some converted to urobilin and some to brown stercobilin which is responsible for colour of faeces
how do bile salts work?
amphipathic- their hydrophobic domains bind to surface of fat globule and hydrophilic domains face outwards- so dietary triglycerides and other lipids emulsified into tiny emulsion droplets in duodenum
how are fats digested and absorbed?
associate with bile salts to form tiny emulsion droplets- greatly increases SA for attack by lipases. pancreatic lipase (in association with helper protein colipase) hydrolyses triglyceride within emulsion droplet to 2 FFAs and 1 monoglyceride. + addition of more bile salts -> eventual production of micelles which ferry products of fat digestion to brush border and enter epithelial cells either by simple diffusion or transport proteins
how does cholesterol enter enterocytes?
special transporters
effect of plant sterols on cholesterol absorption?
prevent it by displacing cholesterol from mixed micelles
export of fat from gut epithelial cells?
fat digestion products + cholesterol bind FA binding proteins within epithelial cells of SI and are delivered to ER where they are converted back into triglycerides- combined with apolipoproteins, phospholipids and cholesterol to form chylomicrons (type of lipoprotein particle). chylomicrons exported from Golgi apparatus, released by exocytosis to enter central lacteals of villi, enter venous circulation via thoracic duct
location and role of lipoprotein lipase?
bound to capillary walls in tissues including muscle, fat, lactating mammary gland. catalyses hydrolysis of triglycerides within chylomicrons to release FAs that diffuse into cells + chylomicron remnants and glycerol that are taken up by liver
what happens to most dietary triglyceride?
ends up in adipocytes. when blood glucose low some is hydrolysed to release FFAs
why does liver secrete VLDLs when fasting?
means of exporting triglyceride and hepatic cholesterol to the tissues
what are the ketone bodies?
acetone, acetoacetate, β-hydroxybutyrate
length of human SI in vivo?
3-5 metres long
how long does chyme take to pass through human SI?
2-5 hours
what does terminal ileum empty into?
large intestine at junction of caecum and colon- projecting lips referred to as ileocaecal valve
what happens in gastroileal reflex?
ileal motility enhanced in response to signals from a full stomach
what happens in colonileal reflex?
inhibits movement through sphincter when colon is full
parts of the large intestine?
caecum, ascending, transverse, descending, sigmoid colon, rectum, anal canal
length of large intestine in humans?
1.5m long
how many taenia does the colon have?
3
where in colon is faeces stored?
transverse colon
roles of large intestine?
store, mix and process contents, expose contents to microbes and absorb nutrients from microbial fermentation, expel waste as faeces
large intestinal motility?
ICC within circular muscle generate 3-6 slow waves/minute- duration of these can be prolonged by ACh
transit time through colon?
usually 1-2 days
why is transit time through colon so slow?
most colonic movements are low-amplitude contractions, propel contents slowly in retrograde direction giving time for fluid absorption
what are HAPCs in colon?
high-amplitude propagating contractions which accelerated forward movement of colon contents periodically. associated with relaxation of haustra
what is the internal anal sphincter?
thickening of the circular smooth muscle just inside the anus- has own myogenic tone modulated by ANS
what is the external anal sphincter?
made of striated muscle, under somatic motor control, tonically contracted- tone will increase with rise in intra-abdominal pressure
what happens when the rectum fills?
sensory nerves send signals to sacral spinal cord- responds via autonomic fibres in pelvic nerves resulting in highly propulsive movements. internal anal sphincter relaxes, external sphincter may be voluntarily relaxed, relaxation of pelvic floor muscles lowers anus straightening angle between rectum and anal canal, defecation aided by Valsalva manoeuvre
what is lacking in Hirschsprung’s disease?
ENS ganglion cells in descending colon and internal anal sphincter - so reflex relaxation of rectum and internal anal sphincter can’t occur when rectum fills- colon dilates and may perforate
effect of opioid receptors in the GI tract?
when stimulated by endogenous transmitters such as β-endorphins promote effects including decreased propulsion, decreased secretion, increased sphincter tone
gut bacterial metabolism
bacteria will metabolise any carbohydrate that gets through to colon and produce VFAs which represent energy source for colonic cells- represents colonic salvage of energy that would otherwise be lost. also synthesise Vitamin K + B vitamins
what does a high-fibre diet do?
substrate for metabolism of beneficial gut bacteria, relieves constipation, promotes satiety, protects against bowel cancer
why does lactose intolerance cause diarrhoea?
undigested lactose reaches colon, colonic bacteria thrive and produce metabolites that cause osmotic water retention, diarrhoea and excess gas (some H2 which is absorbed and exhaled on breath)
role of appendix and caecum?
appendix has mucosal walls with lots of GALT- local defence against infection which may assist with maturation of B lymphocytes and production of IgA antibodies. may be store of beneficial microbes used to re-inoculate gut after diarrhoea
what is flatus?
gas in the digestive tract
average composition of flatus?
50% N2, very small amount of O2, 25% H2, 15% CO2, 10% methane. odour from hydrogen sulphide + methyl sulphides mostly
constituents of faeces?
75% water. rest is around 40% bacteria, 15% fat, 2.5% protein, 15% inorganic matter and rest indigestible fibre
