2.12 - Fluid Compartments and Solutes Flashcards
Intracellular vs extracellular ion concentrations
Cation levels:
- Na+ is the most plentiful cation in plasma
- K+ is the most plentiful ion inside cells - neutralised by a variety of anions e.g. proteins, nucleic acids, phosphorylated proteins
Anion levels:
- organic phosphate is the main intracellular ion (needed for ATP production, cell signalling, phosphorylation of proteins for activation/inactivation)
- proteins - many have a net negative charge - even though they are found in relatively low concentrations, they can have a highly negative charge
pH:
- inside of a cell is slightly more acidic than plasma - two fold difference in proton concentration between plasma and intracellular compartments
What is osmolarity?
- osmolarity is defined as a measure of the concentration of all solute particles in a solution (mosmol/l)
- to calculate osmolarity, imagine the compounds dissolving into cations and anions and multiply the number of these by concentration
- biological ion concentrations are usually in the order of mM concentrations so resulting units are milliosmoles/L
- e.g. what is the osmolarity of a solution containing NaCl at 150mmol/L, CaCl2 at 1mmol/L and glucose at 2mmol/L?
- NaCl –> Na+ + Cl- –> 150 x 2 = 300 mosmol/L
- CaCl2 – Ca2+ + 2Cl- –> 1 x 3 = 3 mosmol/L
- glucose –> 2 mosmol/L
- total osmolarity - 305 mmol/L
What is diffusion?
- the spontaneous movement of a solute down a concentration gradient until the solute molecules reach an equilibrium
What is osmosis?
- the movement of water down its own concentration gradient (high water potential to low water potential)
- osmosis moves water toward an area of higher osmolarity
- it can therefore change cell volume with consequences for cell function and survival
- osmoles - the number of moles of solute that contribute to the osmotic pressure of a solution
What happens if the membrane is permeable to both H2O and the solute?
- initially, osmolarity in cell is greater than outside (Osmi > Osmo)
- final state: Osmi = Osmo
- after equilibrium there is no net volume change of the cell
What happens if the membrane is permeable to H2O and solute A but not B?
- initially: Osmi > Osmo
- solute B cannot leave the cell, so remains in the cell
- therefore water moves in by osmosis down its water potential gradient
- after equilibrium, the cell is swollen
What if the membrane is permeable to H2O but not to the solute?
- initially: Osmi > Osmo
- solute is unable to leave the cell, water moves in down its concentration gradient
- after equilibrium, the cell is swollen and may rupture
Is osmolarity an unreliable guide?
- there are three different outcomes even if the initial state is the same (Osmi > Osmo)
- therefore osmolarity is an unreliable guide to the effects of solutions on cell volume
- concept of tonicity is much more useful
What is tonicity?
- tonicity defines the strength of a solution as it affects the final cell volume
- depends on both cell membrane permeability and solution composition
- hypertonic solution - osmolarity of impermeant solutes outside > inside = water moves out = cell shrinks
- hypotonic solution - osmolarity of impermeant solutes outside < inside = water moves in = cell swells
- isotonic solution - osmolarity of impermeant solutes outside = inside - cell volume is unchanged as no net movement
Why don’t cells burst if the concentration of impermeant solutes (proteins) is much higher inside than in interstitial fluid/plasma?
- Na+K+ ATPase pump actively pumps Na+ out of the cell, maintaining a higher concentration of Na+ outside the cell
- water therefore follows and moves out of the cell by osmosis
- ATPase makes membrane effectively impermeable to Na+ as any Na+ that diffuses in down its concentration gradient is pumped back out so there is no net movement of Na+ across the membrane
- intracellular osmolarity of impermeant solutes (mainly proteins at high concentration and low concentration Na+) balances the extracellular osmolarity of impermeant solutes (mainly high concentration Na+)
- Osmi = Osmo
How do solutes cross biological membranes?
- gases and hydrophobic molecules (e.g. steroid hormones) can diffuse across the phospholipid bilayer
- most molecules require particular proteins for transportation across a biological membrane
- this uses ATP hydrolysis in the case of active transport against an electrochemical gradient (e.g. Na+K+ATPase), or is passive, facilitating the flow of molecules down an electrochemical gradient
How does tissue preservation work in transplantation and why is it needed?
- donated organs/tissues needing to be transported to recipient are perfused with cold solutions via arterial supply to reduce deterioration in hypothermia
- when any tissue loses blood supply then ischaemic changes occur which can be slowed by rapid cooling of tissue to 4oC
What happens to the sodium-potassium-ATPase pump during hypothermia?
- Na+K+ATPase stops working below 15oC and with no circulation there is no O2 and therefore little ATP to fuel the pump
- Na+ may enter the cell along with Cl-, and water will enter as K+ leaves
- cell may swell and their membranes bleb –> cell death
What does perfusing the organ with University of Wisconsin (UW) solution do?
- can help protect from sodium-potassium pump causing problems which is formulated to reduce hypothermic cell swelling and enhance preservation
It has three main factors serve to reduce cell swelling: - lack of Na+ or Cl- = no influx
- presence of extracellular impermeant solutes (lactobionate ions, raffinose)
- presence of a macromolecular colloid (starch) - contributes to colloidal osmotic pressure
- allopurinol and glutathione are present and act as antioxidants to protect organs from damage from reactive oxygen species (ROS)
How do molecules cross the endothelial cell layer of blood vessels?
- lipid-soluble substances pass through the endothelial cells
- small water-soluble substances pass through the pores between cells
- exchangeable proteins are moved across by vesicular transport
- plasma proteins generally cannot cross the endothelial cell membranes and cannot get through pores between cells - osmotic effect
