M104 T1 L7 Flashcards
What quantity of water and minerals is lost in faeces?
~200 mL
minimal loss
What processes regulate secretion and absorption?
the osmolarity of the lumen contents
enteric and autonomic signals
endocrine hormones
immunogenic signals
How does the osmolarity of the lumen contents regulate secretion and absorption?
in the absence of food, electrolytes are primarily responsible for creation of an osmotic pressure gradient in gut lumen
this pressure gradient will either draw water and electrolytes into the gut or allow absorption
What processes occur across GI epithelium daily?
bidirectional secretion and absorption
Where are secretions most common?
in the upper GI tract
What volume of secretions are released in the upper GI tract?
~7L
What substances are part of the secretions released in the upper GI tract?
saliva, bile
pancreatic, intestinal and gastric juice (PIG)
What is the role of the secretions released in the upper GI tract?
they facilitate movement along the GI tract
they mix with digestive enzymes
they allow chemical reactions to occur
they allow nutrient absorption to occur
What percentage and quantity of ingested and secreted water and electrolytes are absorbed?
98%
~8.8 L
What substances are predominantly absorbed in the jejunum of the SI?
ingested and secreted water and electrolytes
How is the SI adapted for absorption?
the presence of enterocyte actin microfilaments
has a rapid response to chyme
epithelium in the SI is more permeable than in the LI
increased SA via folds, villi and microvilli
the villi have lymphatics and blood vessels
How does the SI respond to a hypertonic environment?
allows the movement of water into the lumen by osmosis to form isotonic chyme
What is the role of enterocyte actin microfilaments in the SI?
they rhythmically contract to move microvilli for maximum exposure to lumen contents
How does the SI respond to an acidic environment?
rapidly increase of HCO3- rich secretions into the lumen to neutralise the acid
How is the LI adapted for absorption?
the surface is covered with crypts / intestinal glands
contains the bacterial microbiome, which has a role in protein digestion and vitamin synthesis
the epithelium is less permeable than in the SI
Has additional absorptive capacity for water and NaCl
How does the additional absorptive capacity for water and NaCl in the LI work?
if the SI can’t absorb the water and electrolytes presented to it, the LI has a capacity to increase absorption of up to 4-6 litres.
it occurs in exchange for K+ loss
What are the different types of active transport?
1o; runs on ATP hydrolysis
2o; primary pump
How does primary active transport work?
a pump hydrolyses ATP
this provides E to move ions against their electrochemical gradient
How does secondary active transport work?
uses the gradient created by the primary active transport pump, which allows a substance to move against its electrochemical gradient
What is an example of a pump used in primary active transport?
Na+-K+ ATPase pump
What are two examples of types of secondary active transport mechanisms?
Symport: two molecules in same direction
Antiport: two molecules in opposite direction
What is the movement of the two molecules during symport mechanisms?
one moves down a conc grad created by the primary pump
the other moves against this conc grad
What is the movement of the two molecules during antiport mechanisms?
one moves down a conc grad
the other moves in the same direction but against its conc gradient using the E provided by the primary pump
What is the role of the sodium potassium ATPase pump?
to keep Na+ in the cell to remain low
How does sodium potassium ATPase keep Na+ levels in the cell low?
3 Na+ exported and 2 K+ imported against electrochemical gradient using E from ATP hydrolysis by ATPase
Keeps Na+ cytosol concentration low
What affects bidirectional fluid flux under the principles of enterocyte transport?
the tonicity of chyme entering duodenum
What is the polarity of enterocytes like?
they are polarised with an apical and basolateral membrane
How is the free flow of gut lumen contents restricted?
by tight junctions between the entry sites
these tight junctions tend to be more permeable in the proximal SI where the majority of absorption occurs
By what two routes can the transfer of products occur?
transcellular routes
paracellular routes
How are products transfered via transcellular routes?
occurs through the enterocyte itself
may be against conc grad and require ATP
How are products transfered via paracellular routes?
occurs between cells
doesn’t require E
What are the three different types of transport proteins involved in transcellular electrolyte transport?
pumps - against concentrations
channels
carriers
What are the three different types of electrolyte transport?
Passive
Solvent drag
Active
How does passive electrolyte transport work?
down electrochemical gradient through ion channels or carriers or permeable tight junctions
How does solvent drag electrolyte transport work?
water follows Na+ gradient via osmosis, taking other ions
How does active electrolyte transport work?
requires ATP
the Na+/K+ ATPase pump depletes cellular Na + and draws Na + across apical membrane from gut lumen via channel or cotransporter
What is an example of solvent drag electrolyte transport?
in the upper intestine where tight junctions more permeable
What happens when chyme enters the duodenum from the stomach?
rapid osmotic equilibration of the chyme occurs
forms isotonic chyme
into hypertonic chyme
from hypotonic chyme
What happens to hypertonic and hypotonic chyme after undergoing rapid osmotic equilibration?
hyper - water is secreted into it
hypo - water is absorbed from it
What volume of chyme enters the LI?
~2 L
What volume of chyme is excreted from the LI?
100-200 ml
What is the role of tight junctions in the LI?
they prevent back-diffusion of ions into the lumen
this allows for a more complete NaCl absorption, so there is limited loss in faeces
What substances are secreted in the LI?
HCO3- and K+
Why is sodium absorption important?
bc it drives the absorption of ions, organics and water
By what process are Na+ ions absorbed?
basolateral active transport into the interstitial space occurs
How are Na+ ions absorbed?
Na+ is pumped out of the cell into the blood vessels
so there is a low Na+ conc inside the cell
this allows Na+ movement from the gut lumen into the entry site
where it is pumped out and then taken up by the capillary network
What are the mechanisms by which Na+ is taken up from the gut lumen?
passive diffusion
apical membrane carrier proteins
What are the four different pathways for passive diffusion?
Organic substrate Na/glucose co-transporter
Na/amac co-transporter
Na/H antiport
Na/Cl symport (ileum)
How is Na+ and Cl- absorption linked?
Na+ absorption with nutrients provides an electrochemical gradient for Cl- absorption to occur
What is special about Na+ absorption with nutrients?
it is electrogenic
What is the effect of Na+ absorption with nutrients being electrogenic?
leads to net negative charge in the lumen and net positive charge in the paracellular spaces)
What is the dominant mechanism for Cl- absorption in the SI that occurs in the proximal ileum?
Cotransport with Na+
What is the dominant mechanism for Cl- absorption in the SI that occurs in the distal SI?
Counter-transport in exchange for HCO3-
Why is the mechanism for Cl- absorption in the SI most dominant in the distal SI?
bc the conc of Na+ ions in the lumen decreases bc the majority of Na+ ions have already been absorbed
so they won’t interfere with the bicarbonate and chloride counter transport
What happens during the counter transport of bicarbonate and Cl- ions?
they’re synthesised in the cell via carbonic anhydrase
secreted into the gut lumen in exchange for Cl-
Cl- < cell < basolateral membrane < interstitial space
What are the routes by which chloride ions are absorbed in the SI?
down an electrochemical gradient
cotransport with na+
Counter-transport in exchange for HCO3-
What is the process of Na+ absorption in the LI driven by?
Na+/K+ ATPase in the basolateral membrane
How do the Na+ ions in the lumen enter the cells?
Na+ channels (facilitated diffusion)
Na+/H+ transporter
No glucose/amino acid carrier activity
Why is HCO3- secreted during Cl- absorption in the SI?
Cl- absorption is associated with acid production by bacteria
so HCO3- acts as a buffer
What is the effect of tight junctions during chlorine absorption in the SI?
to ensure no ion backflow into lumen
What is the effect of Na+ and Cl- movement during chlorine absorption in the SI?
creates osmotic gradient for transcellular water movement
What happens when K+ ions become concentrated in lumen as water is absorbed from gut?
it may be absorbed down a conc grad or secreted when lumen concentration low (net secretion)
What substances regulate absorption? (GAS)
glucocorticoids, aldosterone, somatostatin
What is aldosterone release triggered by?
dehydration
released from the adrenal cortex
What is the effect of aldosterone?
it acts on the LI to upregulate Na absorption from the gut lumen
How does aldosterone cause the LI to upregulate Na absorption?
it increases in Na+ channel expression in the apical membrane
it stimulates the Na+/K+ ATPase pump
What is the effect of the stimulation of Na+ channels and the Na+/K+ ATPase pump on Na absorption?
there is increased uptake and absorption of Na+ ions from the LI
this occurs at the expense of K+, which are then secreted in in a greater amount into into the gut
What is the effect of glucocorticoid and somatostatin action?
they increase water and NaCl absorption by upregulation of Na+/K+ ATPase pump
How are enterocytes in crypts and villi different?
they express different combinations of transport proteins - indicates a differing role
What is the role of enterocytes on the SI villi?
they are absorptive and dominate nutrient transport
What are the different locations of enterocytes?
on the SI villi
in the crypts
What are the roles of enterocytes in the crypts?
they are secretory with minimal nutrient transport
they secrete water and electrolytes in the SI and the LI
What is the secretion of water and Na+ and Cl- ions driven by?
by Cl- ion channels in the apical membrane
What type of cells are responsible for the secretion of water and Na+ and Cl- ions?
crypt enterocytes
What ions are driven across the basolateral membrane by the Na+/K+ ATPase pump?
Na+, Cl- and K+ ions
What is the role of Na+/K+ ATPase pumps?
to establish a Na+ electrochemical gradient across the basolateral membrane
this drives Na+, Cl- and K+ ions through Na+/K+/2Cl- cotransporters into crypt cells
How do Cl- ions leave crypt enterocytes and enter the intestinal lumen?
via apical Cl- channels including CFTR
How do Cl- ions draw Na+ ions into the lumen?
they provide electronegativity in the intestinal lumen
this creates an osmotic gradient for water movement into the gut lumen via paracellular routes
AAR, Na+ is drawn into the lumen
What causes cystic fibrosis?
a deletion in gene for CFTR channel
What are the genetics of cystic fibrosis?
autosomal recessive
Why is the CFTR channel important?
bc it is the main Cl- channel in the apical membrane of the gut, pancreatic and airway epitheliums
What are the effects of cystic fibrosis?
the secretion of sticky mucus and high viscosity of luminal contents
How does cystic fibrosis present?
with intestinal obstruction and meconium ileus in newborns
What is the cause of a meconium ileus?
when the meconium in a child’s intestine is even thicker and stickier than normal meconium, creating a blockage in the ileum
What condition is meconium ileus associated with?
cystic fibrosis
What is the effect of cholera toxins?
they permanently switch on enterocyte secretion via cAMP
What is the cholera toxin secreted by?
bacteria vibrio cholera
What does bacteria vibrio cholera bind to in the body?
the cell receptor on apical membrane of crypt cells
How does the bacteria vibrio cholera affect adenylate cyclase?
it irreversibly upregulates it
What is the role of adenylate cyclase?
it’s responsible for the excess formation of cAMP from ATP
this stimulates Cl- secretion via the CFTR Cl- channels
What pump does the bacteria vibrio cholera rely on?
the Na+/K+ ATPase pump
What is the effect of the bacteria vibrio cholera physiologically?
a massive Cl- efflux, Na+ and water (via osmosis) into the gut lumen, particularly in the jejunum
Is cholera permenant?
yes
the effects are only reduced after enterocyte turnover
How is cholera treated?
oral rehydration therapy
What does oral rehydration therapy involve?
promotes fluid absorption by coupling Na+ with glucose in solution
Which membrane carrier protein is preserved in most diarrhoeal diseases?
SGLT-1
What is the SGLT-1 membrane carrier protein specific for?
Na+-glucose co transport
How does the SGLT-1 membrane carrier protein work?
it binds two Na+ to one glucose
it transports them into the cell
Cl- follows for electrochemical balance
What is the effect of the action by the SGLT-1 membrane carrier protein?
it replaces salt and water loss from secretory diarrhoea
What is lactose intolerance caused by?
a deficiency in the enzyme lactase
lactose is not digested and remains in the lumen
this creates an osmotic gradient to cause secretion of water
results in osmotic diarrhoea
What are the two components of lactose?
glucose + galactose
How does somatostatin regulate absorption?
upregulates the Na+/K+ ATPase pump = more h2o & NaCl absorbed
inhibits nutrient absorption
What is one of the largest and possibly one of the oldest gene families?
ATP-binding cassette transporters
Where are CFTR channels located?
mainly in the apical membrane of epithelium
What do CFTR channels have a role in regulating?
transepithelial salt and liquid movement
What substances are contained in meconium?
cells, protein, fats, and intestinal secretions, like bile
What is the consistency of meconium?
sticky, thick, dark green
When is meconium typically passed?
in the first few hours after birth or while still in the womb
Where do vibrio cholerae naturally live?
in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and other shellfish
What happens when vibrio cholera bind to the cell receptor on apical membrane of crypt cells?
they irreversibly upregulate adenylate cyclase
What are the short term effects of profuse diarrhoea caused by cholera?
dehydration and resultant circulatory shock
Is cholera dangerous?
yes, it’s life threatening
What happens if cholera isn’t treated?
it leads to permanent effects or death
