Lecture 43: Intestinal Water and Electrolyte Movement

Question 1

What is the role of water in digestion?

Answer 1

• Dissolving water soluble components
• Enzyme function

Question 2

What is the role of water in absorption?

Answer 2

• Diffusion of nutrients to sites of absorption
• Lubrication for effective transit and elimination

Question 3

What is water movement across the cell driven by?

Answer 3

Transcellular and paracellular movement of solutes

Question 4

What are electrolytes?

Answer 4

Particles that carry charge e.g. Na+, K+, Cl-, HCO3-

Question 5

What are osmolytes?

Answer 5

Particles that don’t carry charge e.g. monosaccharides, amino acids, bile salt

Question 6

Describe the difference in capacity and transport of paracellular and transcellular pathways:

Answer 6

Para: high capacity, bulk transport
Trans: Lower capacity, regulated transport

Question 7

What permeability does the paracellular and transcellular pathways depend on?

Answer 7

Para: tight junctions
Trans: apical and basolateral membrane

Question 8

Where does most absorption occur?

Answer 8

Small intestine - bulk absorption

Question 9

Describe the transport mechanisms in the small intestine:

Answer 9

• Leaky TJs allow paracellular bulk transport
• Transcellular provides driving force for some paracellular processes

Question 10

What is water movement in the small intestine driven by?

Answer 10

Passive driven by transcellular movement of electrolytes and osmolytes

Question 11

Describe the tonicity of absorption and secretion in the small intestine:

Answer 11

Isotonic because water can follow until the osmotic gradient is correct

Question 12

How does the transcellular pathway provide driving forces for water and some solutes?

Answer 12

1. Na+/K+ ATPase generates electrochemical gradient for Na+ to enter cell
2. Na+ crosses apical membrane down it’s electrochemical gradient (e.g. via SGLT1) and brings a solute with it
3. Nutrient moves across basolateral membrane down its conc. gradient (e.g. via GLUT2)
4. Cl- drawn into ISF via paracellular pathway to maintain electro-neutrality
5. H2O flux via paracellular pathway due to osmotic driving force

Question 13

Describe the effect of minerals on fluid movement:

Answer 13

Don’t have major influence

Question 14

Describe the absorption of the the mineral, Ca2+:

Answer 14

Actively absorbed in duodenum
* Apical membrane: epithelial Ca2+ channels
* Intracellular: Ca2+ binding proteins
* Basolateral membrane: Ca2+ ATPase

Question 15

Describe the absorption of the the mineral, Fe2+:

Answer 15

Actively absorbed in duodenum
* Apical membrane: co-transported with H+
* Basolateral membrane: exported via ferroportin

Question 16

Where does regulated absorption occur?

Answer 16

Large intestine

Question 17

Describe the transport mechanisms in the large intestine:

Answer 17

• Tight TJs = little or no paracellular transport
• Transcellular pathway is regulated
• Body decides how much of the remaining water, solutes and nutrients are required and absorbed

Question 18

What is water movement in the large intestine driven by?

Answer 18

Passive driven by transcellular movement of electrolytes

Question 19

What conditions change transport in the large intestine?

Answer 19

• Electrolyte transport in the large intestine changes based on the amount of salt in the diet
• Regulated fine tuning of salt uptake by the large intestine is based on need
• Normal salt uptake = electroneutral
• Salt depleted = electrogenic

Question 20

In what animals does electroneutral absorption occur?

Answer 20

Salt replete animals

Question 21

Describe the process of electroneutral absorption:

Answer 21

1. Carbonic anhydrase: generates HCO3- and H+
2. Apical NHE-3 exchanger: H+ recycled by conversion back to CO2 and H2O
3. Cl- absorbed transcellularly via: apical Cl-/ HCO3- exchange (HCO3- recycled) -> basolateral Cl- channels
4. Water movement: NaCl in ISF causes a small amount of paracellular H2O flux via osmosis

Question 22

When is electrogenic Na+ absorption predominant?

Answer 22

Under low salt conditions

Question 23

Describe the process of electrogenic Na+ absorption:

Answer 23

1. Apical Na+ entry via highly selective channel – ENaC
2. Na+ exits via basolateral Na+/K+ ATPase: This and K+ channels creates net charge transfer = electrogenic
3. Cl- follows via paracellular pathway
4. Transcellular water follows salt movement: tight so most water moves via aquaporins

Question 23

Describe the mechanism of aldosterone:

Answer 23

• Binds to gene promotors in colonic epithelial cells to stimulate protein synthesis:
• ENaC subunits
• Na+/K+ pump
• K+ channel
• Serum and glucocorticoid-induced protein kinase (SGK), which cycles ENaC into apical membrane

Question 23

How is electrogenic absorption switched on?

Answer 23

Aldosterone - released in response to low Na+, high K+ and low BP

Question 23

What effect does aldosterone have?

Answer 23

Increases the amount of electrogenic Na+ absorption and total Na+ absorption

Question 24

What produces short chain fatty acids?

Answer 24

Colonic bacteria

Question 24

Describe the intestinal NaCl secretion:

Answer 24

1. Na+/K+ ATPase generates gradient for Na+ 2. Cl- uptake via basolateral NKCC1 - Secondary active transport - Increases intracellular Cl- above electrochemical equilibrium 3. CFTR allows Cl- to move across the apical membrane 4. Paracellular Na+ movement driven by Cl- 5. Osmotic gradient drives paracellular water movement * Results in isosmotic NaCl solution

Question 24

Describe the absorption of short chain fatty acids:

Answer 24

* Na+ absorption via apical SMCT transporter * No need for basolateral transporter - SCFAs are used as energy source for colonocytes

Question 25

Describe how intestinal NaCl secretion is regulated:

Answer 25

Secondary messengers stimulate intestinal Cl- secretion 1. cAMP stimulates CFTR activity - Sustained secretory response - Ligands include VIP (ENS) and prostaglandins 2. Ca2+ stimulates K+ channel activity - Increased driving force for NKCC and Cl- exit via CFTR - Transient secretory response - Ligands include ACh (ENS) and histamine

Question 26

Describe intestinal HCO3- secretion:

Answer 26

1. Na+/K+ ATPase generates gradient for Na+ 2. HCO3- uptake via Na+/HCO3- co-transporter (NBC) - Secondary active transport using Na+ driving force 3. HCO3- moves out of apical membrane via CFTR channel or Cl-/HCO3- exchange (modifying) 4. HCO3- transport drives paracellular Na+ movement 5. Osmotic gradient drives water movement

Question 26

What is the treatment for increasing time for absorption for secretory diarrhea?

Answer 26

* Opioids reduce the size of contractions in the GI tract * They slow down motility, increases transit time through the GI tract meaning more time for absorption * Imodium (loperamide) is an opioid that only binds to the class of opioid receptors in the GIT

Question 26

What is the treatment for increasing driver for absorption for secretory diarrhea?

Answer 26

Oral rehydration therapy / sports drink contain water, glucose, sodium, other electrolites and osmolites and water - Glucose and NaCl increase the driving force for osmotic H2O absorption - NaCl and water replace losses from vomiting and diarrhea