T1 L9 GI salt & water transport Flashcards
How much fluid enters the bowel everyday?
8.5L
How much fluid is reabsorbed by the bowel everyday?
8.4L
What electrolytes are contained in the fluid that is presented to the small intestine for reabsorption?
Na+
K+
Cl-
HCO3-
How much fluid does the small intestine reabsorb everyday?
6.5L
What electrolytes does the jejunum reabsorb?
Na+
K+
Cl-
H2O
What electrolytes does the ileum secrete & reabsorb?
Secretes HCO3-
Reabsorbs H2O
What electrolytes does the colon secrete & reabsorb?
Secretes K+ & HCO3-
Reabsorbs Na+, Cl- & H2O
How is the GI tract adapted for liquid absorption?
Large - bowel is 3-6m long
Folded - villi increase surface area
What is the type of epithelium lining of the GI tract?
Simply columnar epithelium
What epithelial cells make up the intestinal mucosa?
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
What are the functions of the intestinal epithelium?
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
What are the structural properties of enterocytes?
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
What are tight junctions?
Intracellular junctions that restrict the passive flow of solutes after secretion or absorption
Serve as stopgaps that prevent water & solute transport across the membrane
What are the types of epithelial transport?
Paracellular pathway
Transcellular pathway
What is the paracellular pathway?
Between the cell
Movement of solutes & water through tight junctions
Mainly dictated by electrochemical gradient
What is the transcellular pathway?
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
What are the types of transport proteins involved in transepithelial transport?
Channels
Carriers
Pumps
What are channels?
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
What are carriers?
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
What are pumps?
Transport proteins that move ions & other solutes against electrochemical gradient
Uses energy from hydrolysis of ATP (ATPase)
Na+/K+ ATPase
H+/K+ ATPase
What are the mechanisms of transcellular transport?
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
What are the types of transepithelial transport?
Passive transport
Solvent drag
Active transport
What is solvent drag?
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
Describe Na+/K+ ATPase
Found on basolateral aspect of the enterocyte
Actively drives Na+ out of cell
Creates Na+ electrochemical gradient between enterocyte & lumen
Describe Na coupled transport
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-
Describe an oral rehydration solution
Mechanism of glucose-coupled sodium absorption
Promotes fluid absorption
SGLT-1 is preserved in most diarrhoeal diseases & forms basis for oral rehydration therapy
What is SGLT-1?
Sodium glucose transport protein found in small intestinal mucosa
Binds 2 Na+ to 1 glucose molecule & transports them into the cell
Describe NaCl transport
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
Describe chloride secretion
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)
What drives the Na gradient to allow Cl secretion through apical CFTR channel?
Na+/K+ ATPase
What is chyme hypo-osmotic?
Water is absorbed through intestinal mucosa into the blood of the villi
What is chyme hyper-osmotic?
Water is transferred by osmosis to make chyme isosmotic with the plasma
Describe the absorption of water
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
Where does water absorption occur through?
Tight junctions
Ion channels with active solute absorption by hydrostatic pressure
Apical Na+ or glucose transporter
Describe water absorption in the jejunum
Highest absorption of Na+ coupled with nutrient absorption
Solvent drag is an important mechanism
Describe water absorption in the ileum
Highest absorption of NaCl
Describe water absorption in the colon
Na+ channels on apical side of the cell
K+ on apical side
Aldosterone
What is aldosterone?
Mineral corticoid secreted by the adrenal cortex
1) Increases synthesis of Na+ channels
2) Increases K+ secretion
3) Hypokalaemia
Describe the nature of the absorbing epithelium
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
How is Na+ reabsorbed in the jejunum?
Co-transport with amino acids (secondary active transport)
Co-transport with glucose (secondary active transport)
Na+/H+ exchange
Na+ channels on apical membrane
How is Cl- reabsorbed in the jejunum?
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-
How is Cl- reabsorbed in the distal ileum & colon?
Via Cl-/HCO3- exchange
What is the consequence of cAMP being stimulated by the cholera toxin?
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
How are SCFA absorbed?
Through monocarboxylate & Na+ coupled monocarboxylate transporters
How is ion transport & secretion regulated?
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
Give some examples of pathophysiological changes of transepithelial transport
Congenital
Acquired - infection, inflammation, hormonal abnormalities etc.
Gastrointestinal infections
Give some examples of bacterial enterotoxins
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
Describe the cholera toxin
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
Describe cystic fibrosis
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
