Week 2 Digestion and absorption 2 Flashcards
What components of the digestive tract are involved in mechanical digestion?
Teeth - chewing
Stomach - chruning and propulsion
Small intestine - segmentation
Large intestine - churning and propulstion
What are the roles of the oral cavity in chemical digestion?
Salivary amylase and lipase
What are the roles of the stomach in chemical digestion?
Pepsin and gastric lipase
What are the roles of the pancreas in chemical digestion?
Amylase
Trypsin
Chymotrypsin
Carboxypeptidase
Elasate
Lipase-colipase
Phospholipase
Cholesterol esterase
What is the role of the gall bladder in chemical digestion?
Store and concentrate bile
What is the role of the intesinatl brush border in chemical digestion?
Enterokinase
Maltase
Lactase
Trehalse
Isomalatase
Aminooligopeptidase
dipeptidase
What is the role of the large intestine in chemical digestion?
Bacterial fermentaion
What are the four key products of digestion?
Water and ions
Amino acids
Monosaccharides
Fatty acids
What is the role of bile stalts in chemical digestion?
Breaks down fat molecules into smaller molecules for enzyme action
How does absoprtion vary across the GIT?
Very limited in the oral cavity - some glucose gels and drugs
Limited in the stomach (some lipid soluble e,g medication and alcohol)
Majority in the small intestine
What substances are normally absobred in the small intestine?
Water
Electrolytes Na+ K+ cl- Ca2+, Mg2+ Fe 2+
Vitamins
Fatty acids
Glycerol and cholesterol
Amino acids or oligopepetides
Monosaccharides
What is absorbed in the large intestine?
WAter, Na+, K+, Cl-, Vitamin K
What are the different sources of carbohydrates that may be broken down in the GIT?
Startch - potatoes, pasta etc
Trehalose - 2 sugar molecues found in mushrooms, honey and yeast
Lactose - milk and dairy products
Sucrose - table sugar
Describe how staract is broken down by enzymes?
Starch is first broken down by alpha amylase from saliva
Into maltose, alpha dextrins or maltotriose
THese are then broken into glucose by their subsequent enzymes
Maltase, alpha-dextrinases and sucraose
How is trhalose broken down?
By enzyme called trehalase into gluxose
How is lactose borken down?
By an ezyme called lactase
Into glucose and galactose
How is sucrose broken down?
By sucrase
INto glucose and fructose
What are the different types of lipids?
Triglycerides
Cholesterol ester
Phospholipids
How are triglycerides broken down?
By lingual, gastric and pancreatic lipases
Into monoglycerides and 2x fatty acids
How is cholesterol ester droken down?
By cholesterol ester hydrolase
INto cholesterol and a fatty acid
How are phospholipids broken down?
By phospholipase A2 into
Fatty acid and lysolecithin
How is protein broken down?
IN the somtach pepsin breaks down protein into amino acids and oligopeptide
In the small intestine acited on by more luminal and brush border enzymes to by broken down into amino acids, dipietides and tripeptides
What are the different luminal enzymes in the small intestine that can act on protein?
Trypsin
Chymotryspin
Elastase
Carboxypeptidase A and B
What are the different brush borbder enzymes that can act on peptides in the lumen of the small intestine?
Peptidases
How is the flow of substances from the pancreas into the duodenum controlled?
Flow into the ampulla of vater then out through the major duodenal pappila
Exit into the duodenum is controlled by the sphincter of Oddi
What are the two principle cell types contributing to secretions in the pancreas?
Pancreatic acinar cells
Pancreatic duct cells
What is the role of pancreativc acinar cells?
Enzyme secretion - proteases, pnacreatic lipase and pancreatic amylases amylase
Immautre enzymes are stored in zymogen granules
also secrets fluid containing salts
What are zymogen granules?
Found at the apical side of the pancreatic acinar cells
Contain enzyme precuroses in the inactive form
What is the role fo pancreatic duct cells in digestion and absorption?
HCO3- Bicarbonate secretion and water
What molecules timulate the release of enzymes from pancreatic acinar cells?
VIP
Secretin
CCK
Ach
Describe how acetylcholine can activate enzyme ssecretion from pancreatic acinar cells.
Activates a GPCR
Leads to activation of phospholipase C
1. Leads to increase in activate DAG - stimulating Ptorein Kinase C
2. Causes IP3 stimulates release of Calcium ions from the ER - stimulate protein Kinase C or Calcmodulin which then activates Protien Kinase or phosphoprotein phosphatases
Leads to fusion of zymogen granules with the cytoplasm for release
Give the basic activation of pancreatic acinar cells to release enzyme
Stimulates with acetylcholine or cholecystokinin along others
Leads to an increased in intraceullar Ca2+ and stimulates the exocytosis of zymogen granules which contain the secertory enzymes
Describe how VIP and secretin lead to the activation of pancreatic acinar cells?
Stimulate a G protein
Activates adenylate cyclase - leads to conversion of ATP to cAMP
Activates Protein KInase A causing the fusion of symogen granules
How does cholecystokin lead to the activation of pancreatic acinar cells?
By two pathways both involiving a G protein activation
1. Activation by andelyaste cyclase, cAMP and Protein Kinase A pathway
2. Activation of phospholipase C leading to calcium ion release activating PK and PP or DAG activating PKC
Results in fusion of zymogen granules with the cell membrane
What is meant by autodugestion?
When pancreatic enzymes destroy own tissue leading to inflammation
How do we prevent auto-digestion?
Zymogen granules contain inactive precursors to prevent autodigestion
The interior of the symogen granule is very acidic whilst enzymes such as trypsin typically require pH 8 to work
Contain Serine Protease INhibitros e.g SPINK1 gene disrupt the activation site to prevent activation inside the granule
What gene is associated with hereditary pancreatitis?
SPINK1
Describe the process of trypsin release and activation in the pancreas
- Proenzymes contained in acinar cells
- released into pancreatic duct and into duodenum by the Ampulla of Vater, commonly trypsinogen
- Trypsinogen is activated by cleave to trypsin by enteropeptidase in the duodenal brush border
- Trypsin can further cleave trypsiongen to active trypsin form
What is trypsinogen?
An inactive precurose of trypsin released from the pancreas.
Activated to trypsin by cleavage by enteropeptidase in the duodenal brush border
What is the role of trypsin in the pancreas?
Cleaves and activates other proenzymes
Chmotrypisinogen to chymotripsin
Proelastase to elastase
Procarboxypeptidase to carboxypeptidase
How does trypsin result in active pancreatic lipase?
Cleaves procolipase into colipase
Which then binds to pancreatic lipase to form an active pancreatic lipase
Describe how hromone stimulation can cause pancreatic acinar cells to secrete salt rich fluid.
Action of ACh and CCK on receptors
results in a rise in intracellular calcium ions
Stimulates protein kinases fueling the loss of Chloride ions through the apical membrane into the lumen and the loss of potassium ions by the apical membrane
How can protein channels in the pancreas lead to the secretion of salt rich fluid?
The sodium potassium pump on basolateral membrane creates a low conc gradient of Na+ intracellularly
Fuels the inward movement by the Na/K.Cl cotransporter in the basolateral membrane.
Hormonal stimulation by Ach and CCK cause a rise in intracellular calcium stimulating protein kinases leading to the activation of chloride channels on the apical membrane (secretion into lumen) and posttasium ion channels on the basolateral membrane
The movement of Cl- creates a more negative voltage in the lumen this causes inward movement of Na+ by paracellular pathway
THis increases osmolarity and encourages the inward movement of water by osmosis
What is the purpose of the pancreatic acinar cells secreting fluid alongside enzymes?
The fluid is isotonic and plasma like.
NaCl rich - hydrates the protein dense material secretied by acinar cells
This prevents dehydration and allows transport in the GIT
What is the main process of HCO3- fluid excretion in pancreatic duct cells?
- CO2 and H2O in teh cytosol are converted by carbonic anhydrase to H+ HCO3-
- HCO3- is transported out the apical membrane by a chloride bicarbonate antiporter
- The chlorine gradient needed for this is supplied by the CFTR protein which transports out bicaronate and chloride ions
- The accumulation of anions drives the movement of water and sodium into the lumen paracellulary down osmotic and potential gradients
5> results in HCO3- rich isotoninc fluids
What additional membrane exhanges aid the secretion of HCO3- by pancreatic duct cells?
Na+ H+ Antiporter - removes excess H+ in echange for for Na+ prevents acidity and allows continued reaction of CO2 and H2O
NKCC1 - supplies Cl- for CFTR
Na+ K+ pump maintains the con gradient for inward sodium flux
Inward flux through Na+ HCO3- cotransporter to maintain HCO3- intracellular supply
K+ channels - efflux K+ on basolateral side - maintain a negative cell voltage
What is the role of CFTR?
How is it activated?
Co-transport of HCO3- and Cl- ion out of the apical membrane of pancreatic duct cells
Maintains CL- gradient for chloride bicarbonate antiporter
Is activated when secretin stimulates cAMP
What is the role of the fluid secreted by pancreatic duct cells in the GIT?
Is high HCO3- isotonic fluid
Prevents changes in stool volume
Neutralises acidic chyme arriving from the stomach, creates optimum pH for enzyme action
What happens when CFTR is mutated?
results in Cystic fibrosis - significant reduced ductal secretion
Unable to secrete HCO3- fluid from duct cells
Protein secretion remain concentrated and precipitated within the duct lumen
BLocks duct and destroys the gland
Can lead to pancreatic exocrin insufficiency
What genetic consition is associtaed with stomach acid hypersection with complications in the duodenum?
Zollinger-Ellison syndrome
Results in duodenal ulcerations
What is the ideal Ph of pepsin, why is this relevant?
Around 2.5
Stomach environment is pH 1-3.5
What is the ideal pH of amylase?
Why is this relevant?
Around pH 7
pH: 6.2-7.6 in the oral cavity
What is the optimal pH for trypsin and why is this relevant?
Around ph9
Small intestine pH ranges from 6-9
What stimulates secretin release?
Acidic chyme entering from the stomach- stimulates S-cells in duodenum and jejunum to release secretin when the luminal pH falls below 4.5
What is the role of secretin?
Increases HCO3- secretion from the pancreatic duct, Brunners gland and the billary ducts
Stimulates bile secretion in the billary ducts
Descreases H+ secretion from pariteal cells by inhibiting gastrin release
Decreases stomach motility
Constricts the pyloric sphincter
Why is the role of secretin important?
natures antacid
Aids neutralising activity and reduces acidic environment factors
Creates optimal conditions for enzymatic digestion of food
Enables enough time for sufficient digestion and absorption and reduces the risk of ulceration from stomach acid
What is the role of CCK in regards to optimising digestion and absorption?
Contracts the pyloric sphincter, slowing the rate of chyme release into the duodenum
Slower passage through the SI, increases time for absorption and digestion
What are gastrointestinal secretions like when people are not eating?
Very low basal rate in the absencse of stimulation
What are the three phases that can stimulate gastrointestinal secretion during a meal?
Cephalic - external environent and mouth
Gastric - stomach
Intestinal - intestine
These can be a mix of endocrine and neural signals.
What is stimuli for gastrointestinal secretions in the cephalic phase?
Sight, smell and taste of food activates chrmorecpeotrs and mechanorecptors in the tongue, oral and nasal cavity.
Anticipatory signals or feedforward control to prepare the GIT to receive food
What are the gastrointestinal secretions resulting from cephalic stimulation?
Salivary, gastric and pancreatic secretion
_ lubrication of passage
- ensures acid present to digest food and kill bacteria
- bicarbonate present to neutralise chyme escaping stomach
- active enzymes in place when the food arrives
What is the role of the stomach in cephalic phase of stimulating gastrointestinal secretions?
Acted on by Conditioned reflexes
Chemorecptros and mechanorecepotrs int eh oral and nasal cavity activate vagal nucleus by afferent pathways.
Vagus nerve efferents cause secretion in the stomach as part of parasympathetic response
How does the vagus nerve act directly on the stomach?
Release of Ach stimulates parietal cells for acid secretion
Release of Gastrin releasing peptide stimulates G cells for gastrin release
What effects the extent of the cephalic phase activation of gastrointestinal secretions?
Nature of the meal
Self appetising self-selected meal increases salivation more than a bland meal
How is the pancreas effected in the cephalic phase of gastrointestinal secretions?
Afferent impulses travel to the vagal nucleus
Vagal efferent transmitto the pancreas duct and acinar cells
Stimulation be ACh which has a greater effect on the enzymatic components rather than the aqueous component
What is the role of the stomach is the gastric phase activation of gastrointestinal secretions?
1) distention activates mechanrecepotrs sneding signalns by vagal afferents to vagal nucleus, efferent signals really back to G cells - this is a cholinergic mechanism
2)Amino acids/peptides activate G cells, Gastrin stimulates stomach acid secretion, this is inhibited below a pH of three due to protein being digested.
What is important abour the gastirc phase in relation to the stimulation of gastrointestinal secretions?
Distention and protein presence are proportional to the size of the meal
Ensures acid response is sufficient
What dietary factors (besides protein) can stimulate acid secretion?
Coffee - stimulates acid secretion
Ca2+ - stimulates gastrin and acid release
Alcohol - stimulae gastrin and acid in some species unsure of effects in humans
What is the effect on the pancrease in the gastric phase of gastrointestinal secretions?
As in cephalic phase
Parasympathetic activation initiated by vagovagal reflex - ACh stimulates pancreatic duct and acinar cells
What is the role of the gastric acid in the intestinal phase in gastrointestinal secretions?
Gastric acid enters intestine (Duo)
Stimulates secretin release - stimulates water and HCO3- release from duct cells and decreases acid secretion
What is meant by aqeous secretions from the pancreas?
HCO3 - and water
What are the main hormonal stimulants of pancreatic activity?
CCK and Ach
What is the role of CCK in the intestinal phase of gastrointestinal secretions?
Fat and protein digestion products stimulate CCK release from I cells
Stimulates vagal afferents initiating vagovagal reflexes
Stimulates the activity of acinar and duct cells in the pancreas
Acts as a negative feedback as active trypsin inhibits CCK release
What are the key differences between endocrine and neural communication?
Neural - faster and short lasting, tissue specific
Endocrine - coordinate activity of multiple tissues, slow acting but have a longer duration
What stimulates the release of Gastrin?
Small peptides and amino acids
Distention of the stomach
Vagal stimulation - ACh
What are the effects of gastrin release?
Increase H+ secretion
Stimulates growth of gastric mucosa
Where is gastrin secreted from?
G cells in the stomach
Where is CCK secreted from?
I cells of duodenum and jejunum
What triggers the secretion of CCK?
Small peptides and amino acids
Fatty acids in the small intestine
What is the effect of CCK secretion?
INcreases pancreatic enzyme and HCO3- secretion
Stimulates contraction of galll bladder and relaxation of the Sphincter of Oddi
Stimulates growth of the exocrine pancreas and gallblaffer
Inhibits gastric emptying
What stimulates the relase of secretin?
H+ in the duodenum
Fatty acids in the duodenum
Where is secretin released from?
S cells of the duodenum
What are the effects of secretin release?
Increased pancreatic and billary HCO3- secretion
Decreased Gastric acid ssecretion
Inhibits effect of gastrin on mucosa
Where is GIP secreted from?
Duodenum and jejunum
What stimulates the release of GIP?
Fatty acids
Amino acids
Oral glucose
What are the effects of GIP secreption?
Increase insulin secretion from pancreatic beta cells
Inhibits gastric acid secretion
Describe how glucose and galactose are abosrbed in the intestinal wall/
- Soidum postassium pump - maintains a low cytoplasmic concnetration of Na+ - sets up concentration gradient
- SGLT1 - co transports glucose/galactose and 2Na+ into the cytoplasm
(Na+ down conc, G/G against conc) - Glucose leaves basolateral membrane down conc gradient through GLUT2 proteins
How would you describe the type of transport that is used for glusoe absorption in the SI?
Secondary active transport
Or co-transport mode with active transport with sodium
Define what is meant by secondary active transport.
Concentration gradient of one molcules provides the energy for the transport of another molecule against its concentration gradient.
Describe how fructose is absorbed in the small intestine?
By facilitated diffusion by GLUT5 in the apical membrane and
GLUT2 in the basolateral membrane.
Describe how oligopepetides are abosrbed in the small intestine?
By secondary active transport by a H+ peptides co-transporter PepT1 - only for small oligosaccharides
These are then broken down by peptidases in the cytoplasm of the enterocytes
Describe how amnio acidsa re absorbed in the small intestine
Some are aborbed by facilitated diffusion by special memnrabe transport proteins
Some are co-abosrbed by secondary active transport along with Na+ ions - this conc gradient is maintained by the soidum potassium pump
Then absorbed through the baolateral side by facilaited diffusion
Describe how fats are absorbed in the small intestine into the epithelial cell.
Bile salts emulsify triglycerides this increases the surface area for lipases
Trilgycerides and monoglyercol is packed into micelles.
Micelles enter the acidic environment created by the Na+ H+ antiporter near the apical epithelium membrane
Protonates fatty acids causing them to level the micelle
Fatty acids can then be taken up by facilitated diffusion by FAT (CD36) or FABPpm or FATPs.
During fatty acid absoprtion what happens to the fatty acids once they have been absorbed into the epithelial cells.
Taken up by the ER
Used to reform new triglycerides by combination with monoglycerol - may say are ressterfied.
Released in the form of chylomocrons through the base of the epithelial cells
Absorbed by lacteals as a component of lymph, enter the blood stream by the thoracic duct (too large to enter between endothelial cells directly)
What is the role of the micelle in fat digestion?
Products of lipid digestion such as cholesterol, lysolecithin and free fatty acids and mixed with bile salts to form micelles
Bile salts are amphipathic - hydrophilic portion arranges to dissolve in aqueous portion of the intestinal lumen with the hydrophobic portion surrounding the lipid components within
THis solibilises the lipids
Can then be carried by diffusion to the apcial cells membrane brush border
What is the structure of chylomcirons?
Contains res-esterfied lipids packaged with apoproteins (20% surface), phospholipids make up 80% outside surface, inside consisting of Cholesterol E and TG
Packaged together in secreotry vesicles in the golgi apparatus
Can migrate to the basolateral membrane and be exocytosed
What is abetalipoporteinemia?
Failure to synthesis Apo B - lack of apoproteins
Unable to forms and absorb chylomicrons so unable to absorb dietary lipids
What are the consequences lactase deficiency?
Inability of body to break down lactose into glucose and galactose.
Causes accumulation of nonabsorbable osmotically active solutes - causing water to move into lumen down an osmotic gradient
Can lead to osmotic diarrhoea
Why can lactase deficiency be detected by a H2 breath test?
Lactose is not digested in the small intestine - instead passes to the colon
Colonic bacteria produced H2 when they catabolise lactose
H2 is then breathed out
Why can lactase deficiency not be diagnosed at birth?
In many non-white ethnic groups as in other mammals, lactase activist decreases after weaning - this is regulated by genetics
Lactase persistence - evolved in some mainly white population where non-human milk was a larger part of diet
What is the osmotic concentration normally like in the small intestine compared to the plasma?
Isotonic
What are some of the theroies behind anti-obesity drugs?
Complete digestion of nutrients is needed for absorption
Orlistate inhiibts pancreatic lipase - prevents lipid absorption
Undigested triglycerides cannot cross the enterocyte membrane
Results in staetorrhoea
Can also lead to a deficient in fat soluble vitamins
What is impaired digestion and malabsoprtion in the crohsn disease associated with?
Decreased intake
Decreased intestinal absoprtion
Increased loss in diahorrea
Increased loss in bleeding into the GIT
What are the caues of malnutrition in CD?
- Increased nutritional requirements - due to inflammatory load
- Reduced nutritional intake - nausea, poor appetite and abdominal pain
- INcreased nutrients loss - nutrient malasborption, diarrhoea, vomiting, fistulas
- Surgery - remove absorptive component of the bowel
- Drug therapy - corticosteroids - drug nutrient interactions
What nutritional deficients are common in CD?
Iron
Zinc
Magnesium
Calcium
Vitamin D
Vitamin B12
