T1 L9 GI salt & water transport

Question 1

How much fluid enters the bowel everyday?

Answer 1

8.5L

Question 2

How much fluid is reabsorbed by the bowel everyday?

Answer 2

8.4L

Question 3

What electrolytes are contained in the fluid that is presented to the small intestine for reabsorption?

Answer 3

Na+
K+
Cl-
HCO3-

Question 4

How much fluid does the small intestine reabsorb everyday?

Answer 4

6.5L

Question 5

What electrolytes does the jejunum reabsorb?

Answer 5

Na+
K+
Cl-
H2O

Question 6

What electrolytes does the ileum secrete & reabsorb?

Answer 6

Secretes HCO3-

Reabsorbs H2O

Question 7

What electrolytes does the colon secrete & reabsorb?

Answer 7

Secretes K+ & HCO3-

Reabsorbs Na+, Cl- & H2O

Question 8

How is the GI tract adapted for liquid absorption?

Answer 8

Large - bowel is 3-6m long

Folded - villi increase surface area

Question 9

What is the type of epithelium lining of the GI tract?

Answer 9

Simply columnar epithelium

Question 10

What epithelial cells make up the intestinal mucosa?

Answer 10

Enterocytes
Endocrine cells
Goblet cells
Paneths cells

All cells (apart from Paneths) originate from proliferative zone, migrate & mature up the villus axis
Cells have a turnover rate of 3-5 days

Question 11

What are the functions of the intestinal epithelium?

Answer 11

Barrier - enterocytes
Secretion of digestive enzymes - enterocytes
Nutrient absorption - enterocytes
Water & electrolyte exchange - enterocytes
Mucus secretion - goblet cells
Sensory & endocrine function - enteroendocrine cells
Innate immune function - Paneth cells

Question 12

What are the structural properties of enterocytes?

Answer 12

Epithelial cells are polarised
Apical side - faces lumen. Membrane has microfolds
Basal side - communicates with blood stream & lymphatic lacteals
Lateral side- in contact with neighbouring cells
Apical & basolateral membranes separated by tight junctions

Question 13

What are tight junctions?

Answer 13

Intracellular junctions that restrict the passive flow of solutes after secretion or absorption
Serve as stopgaps that prevent water & solute transport across the membrane

Question 14

What are the types of epithelial transport?

Answer 14

Paracellular pathway

Transcellular pathway

Question 15

What is the paracellular pathway?

Answer 15

Between the cell
Movement of solutes & water through tight junctions
Mainly dictated by electrochemical gradient

Question 16

What is the transcellular pathway?

Answer 16

Through the cell
Membrane transporters move molecules & water through the cells
Activity drives ion flux & establishes concentration gradients
Dictates passive transport of water & solutes
May work against electrochemical gradient

Question 17

What are the types of transport proteins involved in transepithelial transport?

Answer 17

Channels
Carriers
Pumps

Question 18

What are channels?

Answer 18

Fluid-filled pores built of protein aggregates
Hydrophobic outside & hydrophilic inside
Gated - part of the protein that opens & closes to regulate entrance of ions
Ion-specific
Transport based on electrochemical gradient
Cl- or Na+ channel

Question 19

What are carriers?

Answer 19

Proteins that facilitate movement of specific solutes across the membrane through conformational changes
Energy independent transport based on concentration gradient or energy dependent
Transport of single molecule, co-transport or exchange
Na+/H+ exchange
Na+/glucose co-transport

Question 20

What are pumps?

Answer 20

Transport proteins that move ions & other solutes against electrochemical gradient
Uses energy from hydrolysis of ATP (ATPase)
Na+/K+ ATPase
H+/K+ ATPase

Question 21

What are the mechanisms of transcellular transport?

Answer 21

Primary active transport - uses energy to drive ion against electrochemical gradient i.e. Na-ATPase
Secondary active transport - co-transport of molecules with ion transport i.e. Na-Gluc co-transporter
Facilitated diffusion - specific transporters facilitate passive transport across epithelial layer

Question 22

What are the types of transepithelial transport?

Answer 22

Passive transport
Solvent drag
Active transport

Question 23

What is solvent drag?

Answer 23

Water leaks from the lumen through paracellular space to reach osmotic equilibrium on basolateral side
Water pulls additional solutes from luminal to basolateral space
Occurs in upper small intestine where tight junctions are the leakiest

Question 24

Describe Na+/K+ ATPase

Answer 24

Found on basolateral aspect of the enterocyte
Actively drives Na+ out of cell
Creates Na+ electrochemical gradient between enterocyte & lumen

Question 25

Describe Na coupled transport

Answer 25

Na+ gradient created by Na+/K+ ATPase allows Na+ coupled transport from the lumen into the cell
Secondary active transport
Process is electrogenic - lumen becomes more negative & drives parallel absorption of Cl-

Question 26

Describe an oral rehydration solution

Answer 26

Mechanism of glucose-coupled sodium absorption
Promotes fluid absorption
SGLT-1 is preserved in most diarrhoeal diseases & forms basis for oral rehydration therapy

Question 27

What is SGLT-1?

Answer 27

Sodium glucose transport protein found in small intestinal mucosa
Binds 2 Na+ to 1 glucose molecule & transports them into the cell

Question 28

Describe NaCl transport

Answer 28

NaCl is absorbed in conjunction with export of hydrogen & bicarbonate
Relies on Na+/K+ ATPase to establish electrochemical gradient
Na/H exchanger works with HCO3/Cl exchanger

Question 29

Describe chloride secretion

Answer 29

Occurs in conjunction with basolateral Na+, K+, Cl- transport
Mainly at level of crypt
Involves coupled import of Na, K, Cl
As Cl- concentration increases, Cl- is secreted via apical chloride channels (CFTR)

Question 30

What drives the Na gradient to allow Cl secretion through apical CFTR channel?

Answer 30

Na+/K+ ATPase

Question 31

What is chyme hypo-osmotic?

Answer 31

Water is absorbed through intestinal mucosa into the blood of the villi

Question 32

What is chyme hyper-osmotic?

Answer 32

Water is transferred by osmosis to make chyme isosmotic with the plasma

Question 33

Describe the absorption of water

Answer 33

Transport of ions, especially NaCl leads the direction of fluid flow across tight junctions
Water is transported through the intestinal membrane by diffusion
Water uptake is coupled with solute uptake

Question 34

Where does water absorption occur through?

Answer 34

Tight junctions
Ion channels with active solute absorption by hydrostatic pressure
Apical Na+ or glucose transporter

Question 35

Describe water absorption in the jejunum

Answer 35

Highest absorption of Na+ coupled with nutrient absorption

Solvent drag is an important mechanism

Question 36

Describe water absorption in the ileum

Answer 36

Highest absorption of NaCl

Question 37

Describe water absorption in the colon

Answer 37

Na+ channels on apical side of the cell
K+ on apical side
Aldosterone

Question 38

What is aldosterone?

Answer 38

Mineral corticoid secreted by the adrenal cortex

1) Increases synthesis of Na+ channels
2) Increases K+ secretion
3) Hypokalaemia

Question 39

Describe the nature of the absorbing epithelium

Answer 39

Intestinal mucosa is highly folded to generate villi
Duodenum has broad, ridge-like villi
Jejunum has tall villi
Ileum has shortest villi
Surface area is increased further by the brush border
Absorption by the epithelial cells occurs on the sides & tips of the villi

Question 40

How is Na+ reabsorbed in the jejunum?

Answer 40

Co-transport with amino acids (secondary active transport)
Co-transport with glucose (secondary active transport)
Na+/H+ exchange
Na+ channels on apical membrane

Question 41

How is Cl- reabsorbed in the jejunum?

Answer 41

1) Na+ reabsorption with nutrients is electrogenic
2) Net negative charge in lumen & net positive charge in paracellular spaces
3) Provides electrochemical gradient for Cl- reabsorption
4) Cl- reabsorption occurs passively through apical ion channels & in exchange for HCO3-

Question 42

How is Cl- reabsorbed in the distal ileum & colon?

Answer 42

Via Cl-/HCO3- exchange

Question 43

What is the consequence of cAMP being stimulated by the cholera toxin?

Answer 43

1) Massive Cl- efflux
2) Na+ ions follow to form osmotically active NaCl
3) H2O secretion follows - more than can be reabsorbed
4) Fluid & electrolyte loss
Treat via oral rehydration therapy

Question 44

How are SCFA absorbed?

Answer 44

Through monocarboxylate & Na+ coupled monocarboxylate transporters

Question 45

How is ion transport & secretion regulated?

Answer 45

Interplay of luminal, hormonal, neural & immunological factors:

• bioactive substances secreted into lumen (neurotransmitters)
• hormones from enteroendocrine cells
• hormones from endocrine cells
• immune cell-derive factors

Infection, inflammation, gut hormones & ENS chemical mediators all regulate transport mechanisms

Question 46

Give some examples of pathophysiological changes of transepithelial transport

Answer 46

Congenital
Acquired - infection, inflammation, hormonal abnormalities etc.
Gastrointestinal infections

Question 47

Give some examples of bacterial enterotoxins

Answer 47

These interact with receptors & signal transduction pathways in enterocytes
Cholera toxin
Heat liable E.coli toxin
Salmonella toxin
Camylobacter toxin
Heat-stable E.coli toxin
Yersinia toxin

Question 48

Describe the cholera toxin

Answer 48

Secreted by Vibrio cholera bacteria
Alters enterocyte function
Causes functional rearrangement of sodium & water transport
Toxin binds gm-1- ganglioside receptors of luminal membrane of enterocytes.
1) Alpha subunit is inserted into the cell.
2) Subunit is inserted into the cell
3) Subunit catalyses ADP-ribosylation of alpha subunit of stimulatory G protein (Gs)
4) Irreversibly activates it & adenylate cyclase activity
5) Increases cAMP
6) Activation of cAMP-dependent protein kinase & phosphorylation of proteins involved in mediating active anion secretion or neutral NaCl absorption

Question 49

Describe cystic fibrosis

Answer 49

Congenital autosomal recessive disease
Deletions in the gene for CFTR, which is the main Cl- channel in the apical membrane
Causes sticky mucus & high viscosity of luminal contents
Often presents as intestinal obstruction & meconium ileum in newborns