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
Which pressures determine solute and fluid movement across a vessel wall?
- colloid osmotic pressure (COP) due to higher concentrations of plasma proteins inside the capillary than outside - draws water in
- hydrostatic pressure inside the vessel due to blood flow through the tissue - forces water/molecules out
- normal capillary - slightly greater hydrostatic pressure than COP = net leakage from capillary
What is oedema and when is it formed?
- leaky capillary - hydrostatic pressure»_space; COP
- oedema - accumulation of fluid within tissues resulting due to imbalance in normal cycle of fluid exchange in tissues –> fluid accumulation in interstitial spaces
- common cause - increased permeability of capillary walls e.g. increased pore size = proteins lost = reduced COP = fluids more readily pushed out
How do lymphatic capillaries help with oedema?
- they collect interstitial fluid destined for return to blood circulation - higher pressure in interstitium than in lymph vessel so fluid moves into lymph vessels from interstitium
- fluid constantly lost from blood vessels, passed into interstitium to be drained by lymphatic vessels
- lymph fluid returns to the circulation either via lymphatic ducts in the subclavian region or via lymph nodes
- when leakage of plasma into interstitium exceeds the capacity of the lymphatics to collect and return it to the circulation, oedema will result as fluid accumulates in interstitial space
What is inflammatory oedema?
- oedema is one of the cardinal signs of inflammation as infectious and inflammatory stimuli often result in it
- local swelling around insect bite
What can cause hydrostatic oedema?
- high blood pressure = increased hydrostatic pressure in vessels = pushes more fluid out of them and can lead to accumulation of interstitial fluid
What can happen to breast cancer survivors in relation to oedema?
- likely to have had axillary (armpit) lymph nodes removed as part of treatment
- this can remove the pathway of drainage from the upper limb on the affected side = accumulation of fluid –> oedema
What is elephantiasis?
- parasitic worms can block lymphatic vessels, preventing drainage of lymph
- here the lymphatics in the right groin are blocked, preventing drainage of interstitial fluid in right lower limb
