Gastrointestinal Systems (Digestive Processes) Flashcards
Where are exocrine and endocrine secretions produced?
Exocrine secretions are produced by epithelial cells lining the GI tract and accessory organs.
Endocrine secretions are produced by endocrine organs/glands.
How do exocrine secretions prepare food for digestion?
By diluting it to the osmolarity of the plasma and altering the pH for optimal digestion
What cells secrete exocrine secretions?
Acini cells
What cells secrete endocrine secretions?
Pancreatic islet cells
What do acini cells secrete?
Exocrine secretions: Enzymes/fluid into the GI tract and out of the body
What do pancreatic islet cells release?
Hormones into the body
Does the pancreas produce exocrine or endocrine secretions?
Both
What is the main cation and anion in plasma?
Na+ and Cl-
What is the main cation and anion in salvia?
Na+ and HCO3-
What is the main cation and anion in the stomach?
Na+ and Cl- (there is no HCO3- in the stomach lumen only protective on GI wall in mucus)
What is the main cation and anion in the pancreas secretions?
Na+ and HCO3-
What is the main cation and anion in the liver and small intestine?
Na+ and Cl-
What secretions have the most acidic pH?
Stomach (all others are slightly alkaline 7.4-7.8)
What is the total volume of secretions in L/day?
8 (majority being from plasma and stomach)
What is the function of saliva?
Oral hygiene, aids in talking, aids in chewing and swallowing by mositening and dissolving food, assists in rendering food isosmotic, pH modulation and contains amylase for starch digestion.
Without saliva you would develop xerostomia which causes dental caries and orla lesions.
What does saliva contain that aids in starch digestion?
Amylase
What is the carrier in vape fluid?
Propylene glycol (PG)
What do the breakdown products of PG include and what is their effect on the mouth?
acetic acid, lactic acid and propionaldehyde which are all toxic to tooth enamel and soft tissue
PG is hygroscopic - what does this mean?
Means water moelcuels in saliva and oral tissue bind to the PG molecules leading to the tissues drying out = results in dry mouth (xerostomia) = less dilution of food from saliva.
What is xerostomia?
Dry mouth
What can a sample of saliva be used to analyse?
DNA
Cancer proteins
Heart attack related proteins
Infection (HIV, COVID, Flu)
What are the three main pairs of salivary glands?
Parotid
Submandibular
Sublingual
*but there is also minor bucca glands in the mouth, pharynx and oesophagus.
What is the main fluid composition of parotid, submandibular and sublingual salivary glands?
Parotid is mainly serous fluid
Submandibular is mixed mucous and serous
Sublingual is mainly mucous rich fluid
What is the primary cite for secretion from salivary glands?
Acinus
What is the cite of modification in salivary glands?
Ducts
What does the isotonic NaCl solution and enzymes of serous acinar cells secretion contain?
Zymogen granules for exocytosis of enzymes
What do intercalated ducts drain from?
Acini
What drains into the mouth?
Striated ducts
What is the function of ducts?
Modification of primary secretions
E.g., Reabsorption of ions from primary fluid to dilute saliva to be more hypotonic
How much saliva is secreted per day?
1.5L
What is the basal rate of saliva secretion (mL.min)?
0.5 mL.min-1
What can increase the rate of saliva secretion 10-fold?
Stimulation
What is the composition of saliva?
Mucus
Digestive enzymes
NaCl/NaHCO3 solution (aka serous fluid)
What is serous fluid?
NaCl / NaHCO3 solution
Where is mucus secreted from?
Sublingual, submandibular and minor buccal glands.
What digestive enzymes are in saliva?
Amylase
Lingual lipase
Where is amylase secreted from?
Parotid gland
Where is lingual lipase secretd from?
Minor salivary glands of the tongue
Where is serous fluid primarily secreted from?
Parotid glands
Lesser extent submandibular
What type of solution is serous fluid?
Hypoosomotic solution of NaCl with slightly elevated K+ and HCO3-.
Is the composition of serous fluid fixed?
No - it varies with rate of secretion.
How do striated and execretory ducts modify fluid?
By the reabsorption of Na+ and Cl-
Striated and excretory duct reabsorption of Na+ and Cl- is without the movement of what?
Without the movement of water
What do ducts secrete a limited amount of?
K+ and HCO3-
What makes saliva always hypo-osmotic?
Na+ and Cl- concentration being less than plasma
K+ concentration being higher than plasma
HCO3- concentration being higher than plasma
Why does osmolarity increase as the rate of secretion increases?
Because there is less reabsorption
How does ion transport in the ducts change?
It doesn’t change - but flow rate does.
More secretion in acini = higher flow rate through the ducts
How does NaCl reabsoprtion change with high and low flow rate?
Low flow rates = greater NaCl reabsorption and more hypotonic saliva
High flow rates = less NaCl reabsorption and more isotonic
Draw the cellular model for secretion in the acini:
Na+/K+ ATPase and the a basolateral K+ channel generate a gradient for Na+ to enter the cell
Cl- uptake via basolateral NKCC1 increases intracellular Cl- above electrochemical equilibrium = secondary active transport (K+ against gradient)
Paracelluar Na+ movement is driven by Cl- and H2O by an osmotic gradient
CFTR allows Cl- to move across the apical membrane
What is the modifications to the cellular model that occur in the ducts enabling reabsorption?
Na+ enters via an apical Na+ channel (ENaC) and exits the basolateral membrane via Na+/K+ ATPase
K+ enters the basolateral membrane via Na+/K+ ATPase and exits via an apical K+ channel
HCO3- and H+ are made bby carbonic anhydrase. HCO3- exits the apical membrane in exchange for Cl- (Cl- recycled via CFTR). H+ exits the apical membrane in exchnage for Na+.
Beause this is a tight eppithelial, water cannot follow the ions / solutes so the solutions ebcomes hypotonic
What is saliva secreted in response to?
Thought of food
Approach of food
Food in the mouth
Things we associate with food
(Autonomic nervous system)
What two reflexes are potentially involved in the regulation of saliva secretion?
Unconditional reflex
Conditional reflex
What is the unconditional reflex of saliva secretion?
An autonomic repsonse due to sight, presence of food in the mouth and repsonse to taste receptors etc
What is the conditional reflex of salvia secretion?
A learned repsonse in which a previously neutral stimulus becomes associated with an unconditional stimulus
What stimulates intestinal Cl- secretion?
Secondary messengers: cAMP stimulation of CFTR activity and Ca2+ stimulation of K+ channel activity.
What ligands are involved in cAMP stimulation of CFTR activity?
VIP (ENS) and prostaglandins
How does Ca2+ stimulate K+ channel activity?
Increased driving force for NKCC and Cl- to exit via CFTR = transient secretoryt repsonse
What ligands are involved in Ca2+ stimualtion of K+ channel activity?
ACh (ENS) and histamine
Is the PSNS or SNS the primary pathway in the regulation of saliva secretion?
PSNS
What is the ionic compositon of saliva dependent on?
Flow rate through the ducts
What are the key components of gastric secretions?
Acid (HCL)
Pepsinogin (converted to pepsin)
Intrinsic factor
Mucus
What is the function of acid as a gastric secretion?
Protective role
Denatures proteins
Provides optimum pH for digestive enzymes in the stomach
Renders fluid isosmotic
What is the function of pepsin as a gastric secretion?
Protein digestion
What is the function of intrinsic factor as a gastric secretion?
Vitamin B12 absorption (DNA, RBC, Pernicious anemia)
What is the function of mucus as a gastric secretion?
Protection - protects against acid and mechanical forces in the stomach
Is the secretory roles of the stomach the same in all regions?
No - different regions of the stomach have different secretory roles.
What are the luminal secretions and function of the LES and cardia region of the stomach?
Mucus and HCO3- therefore protective role
*LES is part of the esophagus
What are the luminal secretions and functions of the fundus and body of the stomach?
Secretes everything so have majority of functions
What is the primary function of the antrum and pyloris of the stomach?
protection because it secretes mucus and HCO3-.
What is the site of acid secretion?
Gastric glands in the body of the stomach
What are the key cells in the stomach lumen?
Mucous cells
Parietal cells
ECL cells
Chief cells
Enteroendocrine cells
What do parietal cells secrete?
Acid and intrinsic factor
What does outflow from glands prevent?
Infection
What do chief cells secrete?
Pepsinogen
What do ECL cells secrete?
Histamine (hormone like function not the allergy repsonse)
What does the volume/composition of gastric secretions depend on?
Whether you are eating or fasting
Approx how much gastric secretions are there per day?
2-3 L
What is fasting?
The time between meals
Is there gastric secretions during fasting?
Yes - mostly by surface cells
What is the osmolarity of gastric secretions during feeding?
Isosmotic - HCl solution produced by parietal cells.
What is the approx final gastric secretion osmoalrity ?
200 mOsmol/L
Are parietal cells scereting at rest?
No
What is the tubulovesicular membrane?
Highly folded membrane within parietal cells that holds the components for acid secretion).
How does the structure of a parietal cell change from being at rest to active?
Disapperance of the tubulovescular system –> it is converted into an extensive intracellular cancliculi
Appearance of large apical microvilli
Increase in surface area of apical membrane
How much does the SA of parietal cells apical membrane increase from at rest to active form?
50-100 fold
What percentage of the protein in the tubulovesicular membrane is H+,K+ ATPase?
80%
What does the conversion of tubulovesicular membrane to canaliculiu allow for?
The insertion (via exocytosis) of the H+,K+ ATPase into the apical membrane - which is the primary active transport responsible for acid secretion.
What does the H+, K+ ATPase do?
It uses ATP to actively transport H+ out of the cell in exchange for K+ into the cell
What are the transport mechanisms in the un-stimulated parietal cell?
Na/K-ATPase (generates the membrane potential and mainatains K+ in cell above equilibrium)
K+ channel in basolateral membrane (recycles K+ and helps generate the membrane potential)
Na+/H+ and Cl-/HCO3- exchanger (pH homeostasis and maintenance of Cl- above equilibirum due to minimum carbonic anhydrase activity).
= essentially there is low activity and not a huge driving force
What are the transport mechanisms in a stimulated parietal cell?
Additional of the H+/K+ ATPase in apical membrane to secrete H+ in exchange for K+.
K+ channel in apical membrane to recycle K+ ions in the lumen to maintain H+ secretion/
Carbonic anhydrase (produces H+ and HCO3- from CO2 and H2O).
Inactivity of the Na+/H+ exchanger in the basolateral membrane
H2O moving via paracellular pathway
What produces a layer of alkaline mucus that protects the stomach from abrasion and acid pH?
The mucus secreted by mucus neck cells in glands and surface cells (HCO3- rich)
What does intrinsic factor bind to and what is the effect?
vitamin B12 - allows for absroption in the ilium
What does histamine act as?
paracrine hormone
How is mucus and HCO3- mucins released from surface epithelial cells?
exocytosis
What is pepsinogin secreted from chief cells activated by?
HCl
What pH is pepsinogin most active?
1-2.5
What pH is pepsinogin inactiavted at?
6
What pH is pepsinogin irreversibly denatured at?
8
What is an endopeptidase?
Means it cuts protien in the middle as opposed to the ends
What hormone is classed as an endopeptidase?
Pepsinogin
What type of protein is intrinsic factor?
Glycoprotein
Why does intrinsic factor need to bind to Vitamin B12?
In order to be absorbed in the small intestine
What are the hormones/neurotransmitters involved in gastric acid secretions?
ACh
Gastrin
Histamine
Somatostatin
What are the three types of hormone signalling that occurs in the stomach?
Neurocrine = chemical signaling that is facilitated by the neurons or nerve cells
Endocrine = hormones travel in blood stream to target cell
Paracrine = signal from one cell to nearby cell
What cell siganlling method is used for ACh?
Neurocrine
ACh is a neurotransmitter
What is the cell signalling method used in the secretion of gastrin?
Endocrine
What is the cell signalling method used in the secretion of histamine?
Paracrine
What is ACh released from?
Postganglionic neurons of the ENS
Where is gastrin secreted from?
G cells located in the antral regions (lower)
Where is histamine secreted from?
ECL cells
What is somatostatin released from?
D-cells
What does somatostatin do?
Inhibits acid secretion
Where are G cells located?
In the epithelial layer of the antrum
What is the antrum of the stomach?
The lowermost part of the stomach
ENS neurons in the stomach wall extent to where?
Parietal, ECL and epithelial cells
Where are ECL cells located?
they sit in the interstitial space near the basolateral surface of epithelial cells in gastric galnds in the body of the stomach
What is ACh released in response to?
Vagal nerve stimualtion involved in external reflexes, long pathway and local ENS reflexes
What is the direct effect of ACh secretion?
Stimulates parietal cells
How does ACh stimulate parietal cells?
By binding to M3 receptors
What pathway is activated when ACh binds to M3 receptor?
Gaq pathway = increase in intracellular Ca2+
What is the indirect effect of ACh release?
Stimulation of ECL cells (therefore release of histamine)
+ stimulate parietal cells
+ small stimualtion of gastrin
How does ACh indirectly stimulate parietal cells?
via cAMP - PKA secondary messeneger and phosphorylation after stimualting ECL cells Gas pathway
What is gastrin produced in response to or stimulated by?
Alot of things but predominately: Products of protein digestion or stimualtion by enteric neurons with the neurotransmitter GRP (gastrin releasing peptide).
How does gastrin cirulate?
In the bloodstream (endocrine)
How does gastrin directly stimualte acid secretion?
Binds to CCKB receptor on parietal cells - Gaq receptors
What is the indirect pathway of gastrin stimulated acid secretion?
Via ECL cells and histamine which stimualtes parietal cells via cAMP - PKA secondary messenger
What is the most potent stimulus for acid secretion?
Histamine
What stimulates histamine release?
ACh and Gastrin
What is the H2 blocker ?
Cimetidine
What does histamine bind to?
H2 receptor (Gas = cAMP - PKA)
Does Gas or Gaq activate the PKA or PKC pathway?
Gas = PKA
Gaq = PKC
What is the effect of PKA and PKC?
Increase transport H+/K+ ATPase from cytoplasm to plasma membrane increasing its activity.
Increase in open probabaility of CFTR (Cl- channel)
What is open probability?
The amount of time the channels in the membrane are open - determinant for permeability.
What effect does an increase in Ca2+ have on transport?
Increase H+/K+ ATPase activity and increases open probability of Ca2+ activated Cl- channels.
What is feedback inhibition generally and specifically in terms of the stomach?
A homeostasis feedback mechanism in which the end product of a process inhibits or controls the process that helped produce it.
In the stomach it refers to the inhibition of acid secretion due to low pH conditons (low pH = acidic).
What is detected in the stomach that causes inhibiroty of acid secretion?
Luminal acid levels - when high luminal acid secretes somatostatin which is an inhibitor.
*luminal acid is the driving force for inhibition
What cells does somatostatin have an inhibitory effect on?
G cells
ECL cells
Parietal cells
What are the two sites of feedback inhibition in the stomach?
antral region (which is the site of gastrin secretion)
body (which is the site of acid secretion)
What is the antrum sensitive to?
The presence of H+ ions in the lumen
What does high acid stimulate D cells to do?
Produce somatostatin
What hormone signalling does somatostatin use?
Paracrine and endocrine
What is the paracrine effect of somatostatin?
inhibits gastrin production by G cells in the antrum
What is the endocrine effect of somatostatin?
Inhibits parietal cells in the body of the stomach
What are D cells stimulated by?
High amounts of gastrin
What is the interdigestive phase?
basal state - resting phase
What is the rate of acid secretion during the interdigestive phase?
Low - follows circadian rhythm (lowest in the morning and highest in the evening)
Compare acid secretion between the cephalic, gastric and intestinal phases:
Cephalic (prep) - ACh key secretion as released in repsonse to actiavtion of PSNS which activates ENS
Gastric - everything happening
Intestinal - mostly reduces secretion due to feedback from duodenum.
What is the difference between endocrine and excocrine secretions?
Endocrine secretion is directly into the bloodstream whereas Exocrine secretions go through the ductal system to epithelial surface.
What is the function of exocrine secretions?
To maintain the composition of the lumen of the GI tract appropraite to its function = maintain osmolarity, pH, water and enzyme content at the correct level.
What are the major components of exocrine secretions?
Electrolytes, Water, Mucus, Enzymes, Acid or bicarbonate to alter pH.
How are exocrine secretions made?
components are produced or transported by epithelial cells and secreted across the mucosal surface of the GI tract lining and the lining of accessory organs.
Are exocrine secretions re-absorbed?
Yes
What type of gland in the pancreas?
Exocrine
What are acinus made of?
Modified secretory epitehlial cells called aciner cells (12-15 cells per acinus).
What is the pancreas the primary site of?
Pancreas is the site of primary isotonic NaCl fluid secretion synthesis and secretion of enzymes
What are acini drained by?
Intercalated duct secretion of biocarbonate rich fluid
What are lobules?
groups of acini which drain into the same interlobular duct - these in turn drain into the main pancratic duct
What are zymogens?
Inactive precursors of digestive enzymes
What cells neutralise acidic chyme from the stomach to form alkaline fluid?
Intercalated duct cells
What is the two step process of pancreatic gland fluid secretion?
(1) Acini production of primary secretion
(2) Ducts modify the secretions
What is primary secretion from acini?
Cl-
And because pancreatic cells are leaky epitehlia Na+ follows and then water follows therefore producing an isotonic solution.
How do the pancreatic ducts modify acini secretions?
They exchange Cl- for bicarbonate resulting in the final product having high levels of bicarbonate.
Draw the cellular model for acini cells in the pancreas:
Cl- uptake via basolateral NKCC1
Cl- move out of apical membrane via CFTR channel
CL- tarnsport dirves paracellular Na+ movement and osmotic gradient drives paracellular water movement
The Na+ and K+ entering cell via basolateral NKCC taken back out via K+ channel and Na+/K+ ATPase.
What is happening in pancreatic ducts as rest?
The ducts are inactive as very little Cl- secretion is occuring in the acini
Draw the cellular model for active pancreatic ducts:
Secretin binds to basolateral membrane which activates cAMP pathway which increases CFTR open probability in apical membrane.
CFTR are continuously recycling Cl- (producted by Acini) meaning bicarbonate is continoulsy secreted into lumen vua the Cl-/HCO3- exchanger.
HCO3- gets there in th efirst place through CA and HBC.
In active pancreatic ducts what results in the fluid being isosmotic?
Paracellualr movement of Na+ and water
What are enzymes secreted as in the ducts?
Zymogens (via exocytosis from the panceatic acini cells)
What are the enzymes for proteins?
Trypsinogen
Chymotrypsinogen
Procarboxypeptidase
What are the enzymes for carbs?
Amylase
What are the enzymes for fats?
lipase and colipase
What happens to proteases in the intestine?
Converted into their active form
What is trypsniogen activated by in the intestines?
Enterokinase (to be converted into trypsin its active form)
When do we have the largest volume of secretion?
Intestional phase
How is secretion regulated by hormones?
CCK - is released in response to nutrients in duodenal lumen.
CCK acts on accessory organs = gall bladder to release bile and the pancrease acinar cells to produce and release primary secretions (pancreatic juices = enzymes).
What is released due to acidic chyme in duodenal lumen?
Secretin
Secretin is produced by S cells in the small intestine (duodenum).
Secretins functions by stimulating the pancreas and liver to secrete bicarbonate-rich fluids.
= When acidic chyme (partially digested food) enters the duodenum from the stomach, secretin is released, triggering the pancreas to release bicarbonate. This neutralizes stomach acid in the small intestine, creating a safer pH for digestive enzymes.
What does secetin stimulate?
Duct cells to modify primary secretion (= exchange Cl- for HCO3-)
In order to do this secretin actiavtes cAMP pathway causing PKA phoysphorylation to inceases Po of CFTR.
Does ACh have any regulatory role in secretion?
Yes - minor regulation of secretion via the long reflex loop (vagus nerve).
What is the key difference between pancrease and salivary ducts?
Pancrease ducts have leaky epithelium whereas salivary ducts are tight epithelium.
This means that in salivary ducts water cannot follow Na absorption therefore get hypotonic saliva - whereas because water can follow Na in pancreas its secretions are iso-osmotic,
What are the 3 steps in bile formation?
(1) primary secretion
(2) secondary modification
(3) storage in gall bladder
Where do hepatocytes secrete bile into?
Canaliculi
Part of the primary secretion in the bile formation process.
hepotocytes = liver cells - this is referring to the transfer of bile from liver where it is produced to gall bladder where it is stored.
What is actively transported into bile?
cholesterol lecithin bulirubin
What is secondary modification of bile production?
Hepatic branch of bile ducts seceting HCO3-
How is the concentration of bile in the gall bladder maintained?
Via reabsorption of NaCl and water
What is the enterohepatic circulation?
Bile salts recycled through a system of active tarnsport in the ileum and transported back to the liver via the hepatic portal vein
What is the biggest stimulus for secretion of bile salts?
Bile salt reabsoprtion - arrival of bile salts in portal venous blood stimulates absorption by liver and subsequent secretion
What percentage of bile is recycled?
95%
How is the release of bile from the gall bladder regulated?
hormonal regulation in the intestinal phase
CCK stimulates the contraction of gall bladder and relaxation of the hepatopancreatic sphincter = bile salt release.
What is a hepatocyte?
Liver cell
What are the main transporters for gastric HCL secretion?
Apical K+/H+ ATPase
Basolateral Cl-/HCO3- exchanger
What is the role of water in the intestine for digestion?
Water is needed to dissolve water soluble components and for some enzymes to function
What is the role of water in the intestines for absorption?
Water is needed for the diffusion of nutrients to sites of absorption.
Also needed for lubrication for effective tarnsit and elimination.
To reabsorb the fluid that is secreted so we don’t beocme dehydrated.
Where does the bulk absorbion of water occur?
Small intestine
Explain small inetsine water flux:
Small intestine has bulk transport as a result of leaky epithelium - leaky means there are TJ that allow for paracellular transport as well as transcellular transport (which creates driving force for paracellular transport).
Explain large intestine water flux:
large intestine has regulated transport - it have tight epithelium therefore little to no paracellular transport of water.
Transport occur primarily via the transcellular pathways are are tightly regulated - the body decided how much of the remaining water, solutes and nutrients are required to be absorbed base on homeostasis feedback loops.
What is transport via transcellular pathway regulated by in tight epithelium?
Aquaporins and TJ proteins
Is water transport passive or active?
Passive = occurs via osmosis driven by the transcellular movement of electrolytes and osmolytes.
What makes absorption and secretion in the small intestine isotonic?
The fact that water can follow until the osmotic gradient is rectified
How exactly does the transcellular pathways create a driving force for water?
(1) Na+K+ ATPase (on the serosal/basolateral membrane) generates an electrochemical gradient for Na+ to enter the cell on apical membrane = primary active transport
(2) Na+ crosses the apical / mucosal membrane into the cell down its concentration gradeint and brings a solute/nurteient with it = secondary active transport
(3) The nutrient moves across the basolateral membrane out of the cell down its concentration gradient = facilitated diffusion
(4) Cl- is drawn into interstitial fluid via the paracellular pathway to maintain electro-neutrality (as a result of the build up of + charge on serosal side due to ATPase).
(5) H2O flux via paracellular pathway due to osmotic driving force from mucosal to serosal.
*1-3 are transcellular process and provide the driving force for 4-5 which are paracellular processes.
What is the primary active transport for water reabsorption in the small intestine?
Na+/K+ ATPase
What is the facillitated diffusion channel for Na+ glucose absorption in the small intestine?
GLUT2
*glucose moves across the basolaterial membrane down its concentration gradient via GLUT2
what is the secondary active transport mechanism for Na+ glucose absorption in the small intestine?
SGLT1
*Na+ crosses the apcial membrane down its electrochemical gradient via SGLT1 and brings a glucose with it.
Is the SGLT2 isoform present in the gut?
No
*only the SGLT1 isoform = which is the high capacity low affinity one.
What may some minerials require for absorption in the small intestine?
Intracellular carrier proteins
Do minerials have a large influence on fluid movement?
No
What minerials are actively absorbed in the duodenum?
Ca2+ and Fe2+
Does Fe2+ require a intracellular carrier protein?
No
What is Fe2+ exported by on the basolateral membrane?
Ferroportin
What is Fe2+ co tarnsported with via the apical membrane?
H+
Where are most osmolytes (monosaccharides, amino acids, bile salts) absorbed?
Small intestine
Does the large intestine have bulk absorption?
No - bulk absorption occurs in the small intestine so the large intestine is just mopping up extras dependant on body homeostasis.
What system is used when you have normal salt status?
Electroneutral
When is the electrogenic system used?
When salt levels are depleted
Explain electroneutral absorption:
Electroneutral absorpiton is where there is no overall change in electrical charge because positive and negative charge reabsorbed in equal amounts - not building up charge on either membrane. Therefore does not require any secretion for electroneuratlity.
Dominant when salt levels are normal therefore not worried about conserving sodium (e.g., increasing apical aborption).
Involves:
Electroneutral absorption involves Na+ and H+ exchange.
Carbonic anhydrase generates HCO3- and H+
Apcial NHE-3 exchanger recycles H+ by conversion back to CO2 and H2O.
Cl- is absorbed transcellularly via apcial Cl-/HCO3- exchanger and basolateral Cl- channels.
NaCl interstitual fluid causes a small amount of paracellular H2O flux via osmosis.
How does Cl- transport differ between electroneutral and electrogenic systems?
Key difference is that Cl- is moved via transcellar mechanisms in electrneutral whereas via paracellular pathway in electrogenic.
Explain electrogenic absorption - with specific reference to Na+ electrogenic aborption:
Electrogenic absorption is where the is an overall change in electrical charge - due to the movement of a ion without the movement of a counter ion.
E.g., Na+:
Apical Na+ entry via highly selective channel = ENaC
Na+ exits via basolateral Na+K+ ATPase
Cl- follows via paracellualr pathway but it is tight epithelium so it is reduced paracellualr permability.
Transcellular water follows salt movement - but brcause tight eptihelium most water moves via aquporins in the cell membrane (transcellular).
*everything moving from apical to basolateral.
How is electrogenic absorption switched on?
RAAS system - aldosterone released in repsonse to low Na+, high K+ and low blood pressure.
Aldosterone has effect on the large intestine and does the same thing as it does in the kidney which is increases gene transcription > SGK > and cycles ENaC into apcial membrane to increase Na+ absorption.
*called electrogenic absorption because the active transport of Na+ movemeent across the membrane contributes to the electrical properties
What is aldosterone released in response to?
low sodium = low BP
What are short chain fatty acids produced by?
Colonic bacteria
What are SCFAs used as an energy source for?
Colonocytes
How is mucous hydrated?
NaCl and HCO3-
Explain the cellular model for intestinal NaCl secretion:
NaK ATPase generates gradient for Na+ = primary active transport
Cl- uptake into cell via basolateral NKCC1 = secondary active tarnsport
CFTR allows Cl- to move across the apical membrane
Paracellular Na+ movement driven by Cl-
Osmotic gradient drives paracellualr water movement
What are the two ways that intestinal NaCl secretion is regulated?
(1) cAMP stimulates CFTR activity
(2) Ca2+ stimulates K+ channel activity
Explain the cellular model for intestinal HCO3- secretion:
Na K ATPAse generates gradient for Na+
HCO3- uptake via na/HCO3- co-transporter
HCO3- moves out of apical membrane via CFTR channel or Cl- HCO3- exchange (modifying)
HCO3- transport dives paracellular Na+ movement
Osmotic gradinet drives water movement
What is the physiological basis of secretory diarrhea?
Caused by e-coli or vibrio cholerae.
E-coli secretes enterotoxin which binds to guanylate cyclase and activates cGMP = increase in CFTR activity = increase the rate of Cl- secretion and the rate of na+ and water movement via the paracellular pathway resulting in isosmotic secretion.
Vibrio cholerae secretes cholera toxin which acts via adenylate cyclase which increase cAMP which also phosphoylates and activates CFTR.
What is the basis of diarrhoea?
Increased isosmotic NaCl secretion
What is the difference between e-coli and cholera?
e-coli = cGMP
cholera = cAMP
How do opioids treat secretory diarrhea?
They reduce the size of conraction in the GI tract and by slowing down motility they increase the transit time through tract meaning = increase time for absorption
Is digestion mechanical or chemical?
both
What are the two stages of chemical digestion?
(1) Luminal Digestion
(2) Contact Digestion
What is the difference between luminal digestion and contact digestion?
Luminal digestion occurs in the lumen of GI tract - uses digestive enzymes to break down large food moelcules.
Contact digestion occurs at the surface of the intestinal epithelial cells (the brush border of the enterocytes lining the small intestine). These enzymes complete the digestion process by further breaking down the products of luminal digestion into their simplest forms (e.g., disaccharides into monosaccharides, peptides into amino acids). This phase is crucial for the final steps before absorption, as it ensures that nutrients are small enough to be absorbed by the intestinal cells.
What is the sterotyped western diet?
low in fruits and vegetables and high in fat and sodium
What is meant by indigenous food systems?
Systems of production, distribution and consumption of foods based on knowledge and practices of indigenous peoples.
What is food sovereignty?
The right of people to healthy and culturally appropriate food produced through sustainable methods and their right to define their own food and agriculture systems.
What is the term for Maori food gathering and cultivation practices?
Mahinga Kai
*It encompasses the value and protection of natural reosurces and is specific to iwi and their rohe.
What percentage of our daily energy intake is carbohydrates?
Approx 50%
Order from biggest to smallest: monosaccharides, polysaccharides and disaccharides.
(1) Polysaccharides (long chains)
(2) Disaccharides (two units)
(3) Monosaccharides (one unit)
What is the most predomiannt type of carbohydrate we ingest?
Polysaccharides = 50-70% of ingested carbohydrates
(then 30-40% are disaccharides and 5-10% monosaccharides)
What type of carbohydarte is glucose and fructose?
Monosaccharide
What are examples of disaccharides?
Sucrose, lactose, maltose, isomaltase, glycoamylase
Starch, glycogen and cellulose are what type of carb?
Polysaccharide
What polysaccharide fiber cannot be digested?
Cellulose
Can polysacchaides be digested by the intestines?
No - only monosaccharides can be digested by the intestines
Where does digestion of polysaccarides occur and via what?
Small intestine lumen via alpha-amylase
*mostly intestinal lumen pancreatic a-amylase
why can cellulose not be digested?
Because it has a B bond and ONLY a bond can be digested
Are polysaccarides digested via luminal or contact digestion?
Luminal
How are disaccharides digested?
Contact digestion by disaccharidases (enzymes)
1) synthesised by GI tract epithelial cells
2) ransported to the apical membrane of the cells
3) function to break disaccharides into monosaccharides at apical membrane
4) monosaccardies are then in close proximity to epitheial transporters
What does lactase do?
breaks down lactose into gluycose and galactose
What are the two mechanisms for absorption of monosaccharides?
(1) Na+ dependant e.g., glucose and galatose via apcial SGLT1 and GLUT2
(2) Na+ independant - absorbed via fcailiated diffusion
What is an example of a carbohydrate that used Na+ independant absorption?
fructose
What is the apcial and basal transporter for fructose?
GLUT5 (apical)
GLUT2 (basolateral)
Explain a lactose intolerance:
Lactose intolerance is the result of not having lactase enzymes - without these enzymes you cannnot digest milk.
Most people loss the ability to produce lactase beyond early childhood - if you can = lactase perisstence.
What do proteins supply?
Amino acids (therefore not normally a major energy source)
What is our relative sources of protein?
50% from diet
25% from discarded cells
25% from secreted proteins
Order from biggest to smallest: oligopeptides, amino acids, proteins, and polypeptides.
Protein - large miomoleucles mod of one or more chains of amino acids.
Polypeptides - long unbranched chains of amino acids
Oligopeptides - smaller unbranches chains of amino acids
Amino acids - single unit
can the body synthesis amino acids?
No
What proteins can be absored in the intestines?
Amino acids and very small peptides (Di, tri and tetra)
What cleaves polypeptides at neutral amino acids?
Pepsin at acidic pH
Explain digestion of protein in the intestinal lumen:
Most peptide digestion happens in the small intestine and results in the release of free amino acids and short peptides
Enzymes are produced by the pancreas and need to be activated by endopeptidases in the intestinal lumin
What are the three short peptides?
Di Tri and Tetra
What are the enzymes that cleave peptides at internal peptide bonds?
Endopeptidases = trypsin, chymotrypisin, elastase
*cuts in middle
What enzymes cleave peptides at C-terminus?
ectopeptidase = carboxypeptidase
*cuts at the end
What type of absorption is used for amino acids?
Na+ dependent
NaK ATPase
Apical Na amino acid cotransporter
basolateral amino acid transporter
What type of absorption is used for peptides?
H+ dependant
involves apical PEPTI cotransporter with H+ creating an electrical driving force
What are 90% of our consumed fats?
Triglycerides
other 10% is sterols, phospholipid and cholesterol
What are fat digestion productions?
Monoglycerides and fatty acids
How are fatty acids and monolgycerides absorbed?
Simple diffusion
What are the steps for the digestion of fat?
(1) Emulsification in the stomach and duodenum
(2) Stabilsaition in the duodenum
(3) Enzymatic digestion in the intestinal lumen
(4) Micelle formation
What is emulsification?
The reduction of the sixe of fat droplets via motility processes of mixing and segmentation
What acts are emulsifying agents to stabilse small emulsion droplets?
Amphipathic bile salts
What does colipase bind to and what is the effect?
emulsion droplets - interacts with lipase which then hydrolyses triglycerides at surface to relase monoglyceride and 2 fatty acids
What does amphipathic mean?
Hydrophillic and hydrophobic parts
Explain micelle formation:
Micelles = smaller droplets that can interact with the brush border for absorption
Why don’t lipids need a transporter for absorption?
Becasue the cell membrane is made up of a phospholipid bilayer with a lipid core threfore lipid soluble molecules such as fatty acids and monoglycerides can move across it freely.
What vitamin is the exception to the rule that vitamins cannot be synthesized?
Vit D - can be synthesised in the skin from cholesterol in light dependant reaction
Do vitamins require digestion?
No
What viatmins are fat soluble?
A, D, E, K
What vitamins are water soluble?
B complex and C
What are lipid soluble vitamines tarnsported in?
Micelles
What does a defect in bile salt secretion result in?
Fat soluble vitamin deficiencies
What are symptoms of viatmin A deficiency?
Night blindness
What are the symptoms of viatmin D deficiency?
rickets and osteoporosis
Explain vit C absorption:
Predominately absorbed in the small instestine via specialised transport proteins: SVCT1 and SVCT2 in the apcial membrane
