Salt and water transport and its control Flashcards
Overview of fluid movement in the GI tract
Net fluid entering: 8.5L/day
Net fluid absorbed by bowel: 8.4L/day
Net fluid loss via stool: 100ml/day
Large intestine absorption
Reabsorbs 2L/day
Jejunum reabsorbs
Na+
K+
Cl-
H2O
Ileum secretes
HCO3-
Ileium absorbs
H2O
Colon reabsorbs
Na+
Cl-
H2O
Colon secretes
K+
HCO3-
Absorption of water
Water transported through intestinal membrane by diffusion
Chyme hypoosmotic
Water is absorbed through intestinal mucosa into blood of the villi
Chyme hyperosmotic
Water transferred by osmosis to make chyme isoosmotic with the plasma
Epithelial lining
Simple columnar epithelium
Heterogenous population of cells
Four major types of epithelial cells making up intestinal mucosa
Enterocytes
Endocrine cells
Goblet cells
Paneths cell
Functions of intestinal epithelium
Barrier: enterocytes
Secretion of digestive enzymes: enterocytes
Nutrient absorption: enterocytes
Water and electrolyte exchange: enterocytes
Mucus secretion: goblet cells
Sensory and endocrine function: enteroendocrine cells
Innate immune function: paneth cells
Structural properties of enterocytes
Epithelial cells polarised
- apical sides face lumen and has microfolds
- basal side rests on basal membrane and communicates with blood stream and lymphatic lacteals
- lateral side is in contact with neighbouring cells
- apical and basolateral membranes separated by tight junctions
Tight junctions
Restrict passive flow of solutes after secretion and absorption
Types of epithelial transport
Paracellular pathway
Transcellular pathway
Transcellular transport
Move molecules and water through cells
Drives ion flux and established concentration gradients which dictates passive transport of water and solutes
May work against electrochemical gradient
Paracellular transport
Movement of solutes and water through tight junctions
Dictated primarily by electrochemical gradient
Channels
Fluid filled pores built of protein aggregates
Gated: have a part that opens and closes and regulates ion entrance
Ion specific
Transport based on electrochemical gradient
Carriers
Proteins that facilitate the movement of specific solutes across the membrane through conformational changes
Energy independent transport based on concentration gradient of energy dependent trasnport
Single molecule, co-transport or exchange
Pumps
Transport proteins that move ions and other solutes across the membrane against the electrochemical gradient
Use energy by hydrolysis of ATP (ATPases)
Exchange
Passive transport
Movement of solutes down its electrochemical gradient
Movement through openings of ion channels, carriers that facilitate diffusion or permeability of tight junctions
Solvent drag
Water leaks from the lumen through paracellular space to reach osmotic equilibrium on the basolateral side
Water flow pulls additional solutes from the luminal to the basolateral space
Takes place in upper small intestine where tight junctions are the leakiest
Active transport
Energy dependent
Transepithelial transport of NA+ using combination of Na+/K+ ATPase on the basolateral membrane
Depletes Na+ inside the cell
Na+ channel or nutrient/ Na+ cotransporter on apical side brings more Na+ in based on the concentration gradient created by the ATPase
Concept 1: Na+/K+/ATPase
Critically important transport found on the basolateral aspect of the enterocyte
Drives sodium out of the cell
Creases a Na+ electrochemical gradient between enterocyte and lumen
Concept 2: Na+ coupled transport
Na+ gradient created by Na+/K+ ATPase allows Na+ coupled transport from lumen into cell
Secondary active transport couples uphill movement of glucose/ aa to downhill movement of Na
The process electrogenic
Oral rehydration solution
Utilising mechanism of glucose coupled sodium absorption
Carrier specific Na+/glucose transporter (SGLT 1) preserved in most diarrheal diseases and forms basis for oral rehydration therapy
SGLT 1 binds two Na molecules to one glucose molecule transporting them into the cell
Concept 3: NaCl cotransport mediated by two transport proteins
NaCl absorbed in conjugation with export of H and HCO3-
Relies on Na+/K+ ATPase to establish electrochemical gradient
Na+/H+ exchanger works in conjunction with HCO3-/Cl- exchanger
Allows NaCl absorption
Concept 4: Cl- secretion occurs in conjunction with basolateral Na+/K+/2Cl- transport
Involves coupled import of Na+/K+/2Cl-
Intracellular Cl- increases so is secreted via apical Cl- channels (CFTR)
Na+/K+ ATPase drives Na+ gradient allowing further Cl- secretion through apical CFTR
Concept 5: water follows NaCl
Transport of ions, mainly NaCl leads to direction of fluid flow across tight junctions
Water will travel through intercellular tight junctions in the setting NaCl absorption
Secretion of water
In the small intestine Cl- secretion drags Na+ and water across the tight junction
(not in colon)
Jejunum transport
The highest absorption of Na+; coupled with nutrient absorption
Solvent drag is an important mechanism
Ileum transport
Similar to jejunum
The highest absorption of NaCl
Colon transport
Apical side: Na+ channels
Apical side: K+ channels
Aldosterone increases synthesis of Na+ channels .. increased K+ secretion.. hypokalaemia
Nature of absorbing epithelium
Intestinal mucosa highly folded to generate villi
- duodenum: broad and ridge-like
- jejunum: tall
- ileum: shorter
Brush border increases surface area
Cholera toxin on electrolyte and H2O reabsorption
CFTR Cl- channel opening regulated by cAMP
Cholera toxin stimulate excess production of cAMP in crypt cells
- massive influx of Cl-
- Na+ follow to form osmotically active NaCl
- followed by h2O secretion- more than can be reabsorbed
SECRETORY DIARRHOEA
Large intestine- water and electrolyte absorption
Driven by Na+/K+ ATPase
Na+ entry by
- Na+ channels
- Na+/H+ antiport
Diffusion under aldosterone control- increases Na+ channels
Cl-/HCO3- provide buffer for acid
Tight junctions ensure no ion backflow
Na+ Cl- create osmotic gradient for transcellular water movement
Na+ transport
Absorption
- through Na+/H+ exchangers
- nutrient coupled
- through electrochemical Na+ channels in distal colon
Secretion
- in small intestine (Cl- secretion drags Na+ and water across tight junction)
K+ transport
Absorption
- through K+/H+ exchangers
- through K+ channels
Secretion
- in colon through K+ channels, increased in pathophysiological conditions
Gastrointestinal infections
Diarrhoea caused by:
- bacterial enterotoxin
- inflammation
Bacterial enterotoxins
Cause secretory diarrhoea by interacting with receptors and signal transduction pathways in enterocytes
- secretion exceeds absorption
Bacterial enterotoxins
Cholera toxin
Heat liable E.coli toxin
Salmonella toxin
Campilobacter toxin
Heat stable E.coli toxin
Yersina toxin
Cystic fibrosis
Autosomal recessive disease
Deletions in CFTR gene
Sticky mucus and high viscosity of lumenal contents
Often presents as intestinal obstruction and meconium ileus in newborns
Lactose intolerance
Lactase deficiency
Lactose not digested so remains in the lumen
Osmotic diarrhoea
