Digestion Flashcards
What are the layers in the gut wall?
mucosa raised into villi > lamina propria > muscularis mucosae > submucosa (and submucosal plexus) > circular muscularis externa > myenteric plexus > longitudinal muscularis externa > serosa
What is the enteric nervous sytem?
Myenteric and submucosal plexus
What does the submucosal plexus control?
Secretion
What does the myenteric plexus control?
Motility
What kind of nervous input is important in the proximal gut? What about further down?
ANS in proximal gut, hormonal and intrinsic ENS control further down
What are some neurocrine transmitters in the GI tract?
ACh, NO, VIP, NA
What are some paracrine transmitters in the GI tract?
Histamine, Somatostatin
What is stimulated in the gut by sympathetic supply?
Sphincters
What transmitters are used in sympathetic supply to the gut?
Cholinergic synapse at ganglion in sympathetic chain or abdominal cavity, then NA synapse in plexi
What carries parasympathetic supply to the gut?
Vagus and pelvix nerves
What neurotransmitters are used in sympathetic supply to the gut?
Both synapses cholinergic
How are sphincters relaxed by the parasympathetic supply?
Inhibitory postganglionic fibres which release transmitters like VIP
Which cells produce secretin and in response to what?
S cells in response to acid
What are the effects of secretin?
Stimulates pancreatic growth, bicarb and water secretion, inhibits gastric acid secretion and motility, promotes sphincter contraction (pyloric)
What does ACh do in the gut?
Excites smooth muscle and secretion
What do NO and VIP do in the gut?
Relax smooth muscle
What does NA do in the gut?
Inhibitory but promotes sphincter and vascular smooth muscle contraction
What is xerostomia?
No saliva
How do hormones help gastric bypass effectiveness?
Hormones peak at different times - increased PYY, GLK-1 which decrease appetite
Which ions does aldosterone affect?
Promotes ion exchange, Na+ reabsorbed, K+ secreted
Which extra glands do dogs have?
Zygomatic
Which species don’t have salivary amylase?
Cats, dogs and horses
What are the different types of saliva?
Serous, mucous or both
What are the glycoproteins in saliva called?
Mucins
What are some ways saliva helps with defence?
Lysozymes, lactoferrin removes iron which bacteria need, IgA, proline-rich protein binds to tannin
Which cells produce primary salivary secretion and where do they secrete it into?
Acinar cells into acinus
What two kinds of ducts modify saliva?
Intercalated and striated
How is saliva modified?
Cl- swapped for HCO3-, Na+ swapped for K+, but reabsorption exceeds secretion
Which cells contract around the acinus?
Myoepithelial
Is saliva hypotonic or hypertonic?
Hypotonic
How does parasympathetic stimulation affect saliva?
Vasodilation, myoepithelial contraction, increased secretory volume
How does sympathetic stimulation affect saliva?
Myoepithelial contraction and increased enzyme contraction
Which cells release gastrin?
From G cells of gastric antrum and duodenum
What is gastrin released in response to?
Nervous stimulation and presence of peptides and amino acids
What does gastrin stimulate?
Gastric acid secretion from parietal cells and promotes growth of oxyntic mucosa
Which cells release cholecystokinin?
I cells in duodenum and jejunum
What is CCK released in response to?
Long-chain free fatty acids and monoglycerides
What does CCK stimulate?
Gall bladder contraction, pancreatic stimulation and growth
What does CCK inhibit?
Gastric emptying and appetite
What are the incretins?
GIP (glucose dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide 1)
Where are the incretins released from?
Upper small intestine (GIP) and jejunum to rectum (GLP-1)
What do the incretins do?
Augment insulin release from pancreas following a meal
What can GLP-1 agonists be used to treat?
Type II diabetes
Where is motilin released from?
M cells in upper small intestine
What happens to motilin release during fasting?
Cyclically
What controls motilin release?
Neural control
What does motilin do?
Initiates MMC
Where is ghrelin released from?
Endocrine cells of stomach
What is ghrelin released in response to?
Fasting
What does ghrelin do?
Works on hypothalamus to stimulate appetite and promotes growth hormone release from pituitary gland
What can peristalsis be initiated by?
CNS (in the oesophagus), slow waves (in the antrum and small intestine) or the ENS (peristaltic reflex, mass movements)
What drives segmental contractions?
Slow waves initiated by ICCs
What does parasympathetic and sympathetic stimulation do to segmentation?
Parasympathetic is excitatory, sympathetic is inhibitory
How does peristaltic release work?
Stretch means mucosal enterochromaffin cells release paracrine serotonin > ENS sensory neurones > myenteric plexus
What do neurones on anal side release for relaxation?
NO with or without ATP
What do neurones on oral side release for contraction?
ACh
What creates the basal electrical rhythm?
Interstitial cells of Cajal
What causes the smooth muscle to contract in the basal electrical rhythm?
Depolarisation causes VG Ca2+ channel to open, reaches contraction threshold, smooth muscle will contract
How do you EXCITE the basal electrical rhythm?
Use ACh to open cation channels to help depolarisation
How do you INHIBIT the basal electrical rhythm?
Use NA to open hyperpolarising K+ channels
What are the three kinds of sensory neurones in the gut?
IPANs, IFANs and sensory fibres with cell body in dorsal root ganglia going gut > spinal cord for stomach reflexes, pain and defecation
What do IPANs do?
Intrinsic primary afferent neurone, sensory, entirely within ENS, afferent part of local reflexes inc. peristalsis, mixing, secretion
What is a vagovagal reflex?
Where both afferent and efferent neurones are carried by the vagus
Which nerves carry pain signals?
Sympathetic
What is referred pain?
Other neurones synapse onto same CNS fibres as gut ones so feels like pain is coming from somewhere else
Where are the sensory afferent fibres from the gut carried?
Vagus
How does the ileal brake work?
Too much fat/nutrients in ileum means not enough absorption and moving too quickly - PYY? GLP-1? IFANS?
What is an IFAN?
Intestinofugal afferent neurone - cell body in gut, neurone which leaves for long distance reflexes from proximal > distal gut (shortcut instead of going through thousands of ENS neurones), goes proximal gut > IFAN > prevertebral ganglion > postganglionic sympathetic fibre
What is the gastro-colic reflex?
Stomach stretch causes colon to move faster - gastrin/CCK?
What is swallowing initiated by?
Touch receptors in pharynx
How does swallowing work?
Bolus to back of mouth, soft palate upwards to block nasal cavity, palatopharyngeal folds limit bolus size, larynx upwards to epiglottis to close it, vocal cords pull together to narrow glottis, respiratory centre of medulla inhibited, upper oesophageal sphincter relaxes, constrictor muscles of pharynx contract sequentially
What is it called when the respiratory centre of the medulla is inhibite?
Deglutition apnoea
What is the chemoreceptor trigger zone?
Area postrema
What muscle makes up the upper oesophageal sphincter? What does it do?
Cricopharygeus muscle prevents air swallowing
What happens if bolus fails to go all the way down the oesophagus?
Secondary wave initiated by persistent distension
What is the process of vomiting?
Increased salivation, reverse peristalsis, close glottis, breathe in, diaphragm and abdominal muscles contract, LOS relaxes
Why is there increased salivation during vomiting?
Alkaline to protect teeth
What can vomiting cause?
Metabolic alkalosis, hypovolaemia, hypokalaemia
What is the lower oesophageal sphincter controlled by?
Inhibitory and excitory ENS fibres
When does the lower oesophageal sphincter relax?
Relaxes before food arrives during feedforward vagovagal reflex
Which transmitter promotes relaxation of the LOS?
NO
What is megaoesophagus caused by?
If ENS neurones are damaged and nothing causes LOS to open so food builds up
What is receptive relaxation?
A vagovagal reflex causing fundus and body to relax in response to stretch so more food can be accomodated with little pressure increase
What is nutrient sampling?
Some food drains into duodenum so there’s nutrient sampling followed by feedback
What does retropulsion in the stomach do?
Breaks in large particles
What lacks ICCs?
Pyloric sphincter
What does the MMC do?
Contractions sweeping food from pylorus > duodenum > terminal ileum
What do cardiac glands produce? Why?
Mucus to prevent acid reaching oesophagus
What do pyloric glands secrete?
Mucus and gastrin into the blood
What do oxyntic glands produce?
HCl, pepsinogens, intrinsic factor and mucus
What converts prochymosin > chymosin?
Acidity
What does chymosin do? Why?
Turns soluble caseinogen into insoluble casein so milk can stay in stomach long enough to be acted on by pepsins
What promotes pepsinogen release?
Vagal ACh and cholinergic reflex in response to acidity
Where is intrinsic factor produced in dogs and cats?
Pancreas
How to parietal cells have such a high secretion rate?
Vesicles and tubules fuse with luminal membrane and luminal membrane is very large
What does B12 bind to? Why?
Haptocorrin to protect from stomach acidity
Where is haptocorrin secreted?
Saliva and stomach
Where does B12 bind to intrinsic factor?
Small intestine
Where is B12 taken up?
Ileum epithelium by receptor-mediated endocytosis
What does gastric acid do?
Delays gastric emptying, improves Ca2+, Fe and B12 absorption, activates pepsinogen, destroys microbes
What happens to gastric acid after a meal?
Na+ decreases, H+ increases but costs energy and may cause ulcers
Which hormones promote acid secretion?
Gastrin, histamine, ACh
Which hormones inhibit acid secretion?
Secretin, somatostatin and prostaglandins
How is gastric acid produced?
CO2 > HCO3- > exchanged for Cl- which goes into stomach and HCO3- goes into the ECF
What is the alkaline tide?
During acid production, bicarbonate added to plasma and CO2 removed causing alkaline tide
Which three substances control acid secretion?
Gastrin, histamine acetylcholine
What promotes gastrin release?
Local stretch receptors via ACh, vagal stimulation via GRP, proteins, amino acids, and Ca2+ in stomach lumen
What is Zollinger-Ellison syndrome?
Gastrin-secreting tumour
What is the strongest agonist of acid secretion?
Histamine
Which cells release histamine?
Enterochromaffin-like cells within gastric glands
What does ACh promote release of?
Acid, histamine and gastrin
What does ACh inhibit release of?
Somatostatin
Which three substances inhibit acid release?
Somatostatin, secretin, prostaglandins
How does somatostatin inhibit acid release?
Effects on ECL and parietal cells
How does secretin inhibit acid secretion?
Indirectly by stimulating vagal afferent fibres
How does secretin affect gastrin release?
Reduces
What do prostaglandins promote production of?
Bicarb and mucus
What happens during the cephalic phase of disgestion?
Feedforward ACh release, acid secretion increases but no pH change because negative feedback through somatostatin and neural reflexes
What happens in the gastric phase of digestion
pH rises, large rise in secretions (gastrin and acid)
Why does the pH rise during the gastric phase of digestion?
Protons buffered by proteins in food
What happens in the intestinal phase of
Duodenal stretch triggers stomach acid secretion, products of protein digestion cause gastrin release, then enteric reflexes and secretin decrease acid production
How are gastric ulcers treated?
Drugs suppressing acid secretion like H2 receptor antagonists and K+/H+ proton pump inhibitors
How does aspirin cause more acid secretion?
Reduced prostaglandins = more acid secretion
How does helicobacter pylori protect itself from acid?
Secretes urease to make ammonia from urea to protect from acid
What promotes relaxation of the pyloric sphincter?
Inhibitory postganglionic vagal fibres which release NO
How are ketamine and alcohol absorbed?
Lipid soluble so absorbed across stomach wall
How is aspirin absorbed?
Weak acid, protonated then diffuses across stomach epithelium
How is gastric smooth muscle contraction increased in the fed state?
ACh and gastrin increase plateau duration and amplitude of plateau
How do neuronal and hormonal reflexes slow stomach emptying?
Inhibit motility or tighten sphincter
What happens in coeliac disease?
Microvilli are destroyed
What are the larger folds of the intestine called?
Folds of Kerckring
What are the Crypts of Lieberkuhn?
Between villi, secrete fluid, contain stem cells
What do pancreatic secretory trypsins inhibitors do?
Found in trypsin granules, protects acinar cells against innappropriate trypsin activation
What does the gastroileal reflex do?
Opens ileocaecal valve, motility enhanced if stomach full
What does the colonoileal reflex do?
Closes ileocaecal valve, inhibits movement through sphincter if colon full
What are Na+ and K+ like in pancreatic juice?
Always high
What happens to pancreatic juice after a meal?
HCO3- increases to neutralise acid and Cl- decreases
What happens in the cephalic phase of pancreatic secretion?
Feedforward vagal ACh
What happens in the gastric phase of pancreatic secretion?
Vagovagal and local reflexes
What happens in the intestinal phase of pancreatic secretion?
Lots of secretin in response to low pH stimulating HCO3- and water secretion, CCK release triggering vagovagal reflexes, enzyme secretion and potentiates secretin
What increases Ca2+ in pancreatic cells?
ACh and CCK
What increases cAMP in pancreatic cells?
Secretin and VIP
Which luminal chloride channels does cAMP open?
Cystic fibrosis transmembrane conductance regulator (GFTR)
What happens to GFTR in cystic fibrosis?
Defective so water doesn’t follow gradient so mucus too sticky
What does cholera toxin do?
Increases cAMP in gut epithelium, permanently activated G protein, CFTR open too much, too much chloride and water secreted, causes hypovolaemia and shock and diarrhoea
Glucose + fructose = ?
Galactose
Which bonds can’t amylases break?
1-6 or the 1-4 either size
What converts oligosaccharides to glucose?
Glucoamylases
What converts alpha-limit dextrins and to glucose?
Alpha-dextrinase
Which transporter for glucose and galactose?
SGLT-1
Which transporter for fructose?
GLUT5
Which transporter takes glucose and galactose and fructose to ECF?
GLUT2
What are the primary bile acids?
Cholic and chenodeoxycholic acids
WHat are the secondary bile acids?
Deoxycholic and lithocholic acids
Which enzyme catalyses trypsinogen to trypsin?
Enteropeptidase
What does trypsin catalyse?
Its own activation, chymotrypsin, elastins and carboxypeptidases
What are the three functions of bile acid?
Fat absorption, waste removal, protection
How is bile used for waste removal?
Cholesterol, bilirubin, heavy metals
How is bile used for protection?
IgA, tocopherol (antioxidant) and mucus
How is bile used for fat absorption?
Bile acids (surfactant) and phospholipids
What is bile acid conjugated with?
Glycine or taurine for solubility, found as Na+ salt
What is the cholerectic effect?
Recycled bile acids stimulate more bile acid secretion but inhibit new bile acid synthesis
What happens to most bile acid?
Some lost in faeces, most taken up and returned to liver by hepatic portal vein bound to albumin and then resecreted
How are bile salts absorbed by the brush border?
Form emulsion droplets, attacked by pancreatic lipase and colipase, form mixed micelle with free fatty acids, cholesterol, phospholipids and monoglycerides, then absorbed by brush border
How does bilirubin travel in blood?
Bound to albumin
What is bilirubin conjugated with before being excreted in the bile?
Glucaronic acid
What’s needed in rehydration salts so SGLT can work?
Water, salt and glucose
What are the two ways of taking up chloride?
Paracellularly or exchanging for bicarb
How does haem > urobilinogen?
Haem > biliverdin > bilirubin > urobilinogen
What converts bilirubin > urobilinogen?
Bacteria
How are urobilin and sercobilin excreted?
Stercobilin in faeces, urobilin in urine
How does urobilinogen > stercobilib?
Oxidised
How does urobilinogen > urobilin?
Reabsorbed and oxidised
What happens if bile duct is blocked?
Faeces lose colour and become fatty, also jaundice because of yellow bilirubin
What happens once calcium enters the duodenum?
Enters down electrochemical gradient, calbindin ferries it to basolateral membrane then it’s extruded into ECF
What upregulates expression of proteins needed for calcium absorption?
D3
What other uptake is needed if high Ca2+ intake?
Paracellular
When is hepcidin produced?
In response to inflammatory mediators
What does hepcidin do?
Reduces gut iron uptake, less circulating iron
What does B12 travel bound to?
Transcobalamin II
What converts Fe3+ > Fe2+?
Fe reductase
What transporter lets Fe2+ into the cell?
Fe2+/H+ cotransporter DMT1
How is Fe2+ transported out of the cell?
Ferroportin
How does Fe2+ travel in blood?
Via transferrin
What happens if hepcidin is present?
Fe is trapped in cell bound to ferritin (removes ferroportin)
How is hepcidin lost?
When epithelial cells are shed
What prolongs the duration of slow waves in the colon?
ACh
In what kind of muscle in the colon are action potentials not needed for contraction?
Circular muscle
What promotes segmental contractions in the colon?
Vagal parasympathetic activity
What inhibits colon motility?
Sympathetic stimulation
What coordinates mass movements?
ENS
What promotes mass movements?
Gastrocolic and duodenocolic reflexes
What kind of muscle is the internal anal sphincter?
Smooth muscle
What modulates myogenic tone of the internal anal sphincter?
ANS
What relaxes the internal anal sphincter?
NO and VIP
What contracts the internal anal sphincter?
ACh
What kind of muscle is the external anal sphincter?
Striated muscle
What controls the external anal sphincter?
Somatic motor control (pudendal nerves)
When does tone increase in the external anal sphincter?
During rise in intrabdominal pressure
What happens following a mass movement from the sigmoid colon?
Internal sphincter relaxes, sensory nerves in rectum cause parasmpathetic pelvic nerves to produce highly propulsive movements, external sphincter voluntarily relaxed, relaxing pelvic floor straightens ano-rectal angle, Valsalva manoevre
Why is there more bacteria in the hindgut?
Less bile
What happens in Hirschsprung’s disease?
ENS ganglion cells are lacking in descending colon and internal anal sphincter, no reflex relaxation of rectum and IAS, colon dilates and perforates
What is raffinose?
Indigestible carbohydrate
What do opioid receptors in the GI tract do?
Stimulated by B endorphins, promote decreased propulsion, decreased secretion and increased sphincter tone
What is a Helminth?
Roundworm, fluke, tapeworm
How does breath hydrogen test for lactose intolerance work?
Undigested lactose in colon causes colonic bacteria to produce H2 gas, some gets into blood and alveolar gas
WHich are the main anaerobic species in the gut?
Bacteroides, Bifidobacterium, Eubacterium
Which way do arterial and venous blood go in the villus?
Arterial blood goes up villus, venous blood goes down villus
Why is there functional hyperaemia after a meal?
Parasympathetic stimulation only increases flow locally
What reduces splanchnic circulation?
Sympathetic vasoconstriction
What empties the central lacteals?
Smooth muscle contraction of lamina propria followed by interstitial pressure increase
What prevents backflow in the lacteals?
Valves
How does liver interconvert amino acids, pyruvate and Krebs intermediates?
Uses transamination
What is a “conditionally essential” amino acid?
An amino acid that can’t be produced fast enough
What can the liver store?
A, D, E, K, B12, and Fe
What does conjugation with glucaronic acid in the liver do?
Makes lipid-soluble compounds water-soluble
What do fat digestion products and cholesterol bind to?
Fatty-acid binding proteins (FABPs) in epithelial cells of the small intestine
What is in a chylomicron?
Triglycerides, apolipoproteins, phospholipids, cholesterol
Where do chylomicrons go from the gut epithelium?
Exported from golgi and released by exocytosis to central lacteal of villi
Where is lipoprotein lipase found?
Bound to capillary walls in muscle, fat and lactating mammary gland
What does lipoprotein lipase do?
Catalyse hydrolysis of triglyerides within chylomicrons
Where do fatty acids go from the chylomicrons?
Transported across endothelium, diffuses into cells where they are resynthesized into triglycerides
What takes up chylomicron remnants and glycerol?
Liver
What secretes very low-density lipoproteins and why?
Liver when fasting to export triglycerides and hepatic cholesterol to tissues
Where do high-density lipoproteins go?
Take cholesterol from tissues > liver
What breaks down insulin?
Kidney and liver
What promotes anticipatory insulin release?
Parasympathetic stimulation of B cells via vagal ACh
What potentiates insulin release in response to oral glucose?
Incretins and certain amino acids
What allows glucose to rise during exercise?
Insulin inhibition by sympathetic stimulation of alpha2 receptors
What is the incretin effect?
Oral glucose causes large insulin increase
How do you get hyperglycaemia during type 2 diabetes?
B cells can fail and die as they can’t sustain extra production
What is the risk in type 1 diabetes?
Unrestrained triglyceride brakdown and high rate of ketone body production = ketoacidosis
How does insulin affect ketone bodies and K+?
Decrease
How does insulin affect muscle?
GLUT4 to cell surface, glucose oxidation and storage as glycogen, fat oxidation and uptake inhibited, stimulates amino acid uptake (anabolic effect)
How does insulin affect adipose tissue?
GLUT4 promotes uptake, conversion to fatty acids stimulated, promotes fatty acid uptake from chylomicrons, inhibits lipase, reduces FFAs
How does insulin affect the liver?
Promotes glucose oxidation, glycogen synthesis and triglyceride synthesis, inhibits fat oxidation, AA uptake, gluconeogenesis, glycogenolysis and hepatic glucose output
What is the standing gradient model?
Solute gradient is set up by pumps and channels, water follows by tight junctions, hydrostatic pressure increases and water is forced out of cleft to be taken up by capillaries
Where is sodium absorption highest?
Small intestine
What is the sodium transporter with monosaccharides?
SGLT1
Which sodium channel is used in the colon?
ENaC
Where is bicarbonate absorbed?
Jejunum
How is potassium absorbed?
Paracellular uptake by small intestine and net secretion in the colon via apical potassium channels
What is the gastrin receptor?
CCKB
