IDTH 201 Cell Volume PDF

**IDTH 201 -- Exam 3 Material** **Cell Volume** **To be in balance, the quantities of fluids and electrolyte leaving the body should be equal to the amount taken in.** What do I mean by that? The energy lost should be equal to the energy gained. Again, the energy lost should be equal to the energ...

**IDTH 201 -- Exam 3 Material** **Cell Volume** **To be in balance, the quantities of fluids and electrolyte leaving the body should be equal to the amount taken in.** What do I mean by that? The energy lost should be equal to the energy gained. Again, the energy lost should be equal to the energy gained in order to keep the internal environment in balance or in a dynamic equilibrium. Loss equals change. **Anything that change the concentration of electrolyte will induce a change in the osmolarity, will induce a change in water content.** I. **Distribution of Fluids in the Body** There is a continuous movement of water and electrolyte between these two compartments ICF and ECF. **A change in electrolyte content and vice versa a change in electrolyte content will induce a change in water content in this compartment.** Total body water content in a male is around 60% of fluids, in female is 50%  - The intracellular fluid compartment includes all the water and electrolytes within cells. - The extracellular fluid compartment includes all water and electrolytes outside of cells (interstitial fluid, plasma, and lymph). - Transcellular fluid includes the cerebrospinal fluid of the central nervous system, fluids within the eyeball, synovial fluid of the joints, serous fluid within body cavities, and exocrine gland secretions. - **Extracellular fluids have high concentrations of sodium, chloride, and bicarbonate** ions, and lesser amounts of potassium, calcium, magnesium, phosphate, and sulfate ions. - **Intracellular fluid has high concentrations of potassium, phosphate, and magnesium** ions, and lesser amounts of sodium, chloride, and bicarbonate ions. ***Hydrostatic pressure and osmotic pressure regulate the movement of water and electrolytes from one compartment to another.*** Water moves from hypotonic to hypertonic (low solute concentration to high concentration). Water moves from high osmotic potential to low osmotic potential. **Osmotic pressure** is the pressure we need to apply to stop the movement of water from one place to another. **Hydrostatic pressure** is the pressure that is created by the fluid on the walls of the container. II. **Cell Volume Regulation** - The movement of molecules from one location to another as a result of their random thermal motion. The molecules of any substance are in continuous state of movement or vibration, *the warmer the substance is the faster its molecules move*. The average speed of this thermal motion also depends upon *the mass of the molecule*. *[Flux is the amount of material crossing a surface in a unit of time]* The net flux between two compartments at any instant is the difference between the two one-way flux. The net flux will determine the net gain of molecule in compartment 2 and the net loss from compartment 1. So the net flux is the total amount of material transferred from one compartment to another. You should keep in mind that the **net flux always goes from the regions of higher concentration to the region of lower concentration**. **What are the factors that regulate the net flux?** - **Temperature**: the higher the temperature the greater the speed of movement. - **Mass of the molecule**: large molecules, greater mass, slower diffusion. - **Surface area**: The greater the surface area between two compartments, the greater the space available for diffusion, therefore greater net flux. - **Milieu**: the medium through which the molecule is moving. The distance over which molecules diffuse is an important factor in determining the rate at which they can reach a cell from the blood or move throughout the interior of a cell after crossing the plasma membrane. **Although individual molecules can travel at high speeds, the number of collisions they undergo prevents them from traveling very far in a straight line**. ***Diffusion times increase in proportion to the square of the distance over which the molecule diffuse***. For example, glucose will take few seconds to reach diffusion equilibrium at a point that is 10 micrometer away from a source of glucose. But it would take over 11 years, 11 years to reach the same concentration at a point that is 10 centimeter away from the source. This is overcome by what we call the circulatory system, which provide a mechanism for rapidly **moving materials over large distances** using a **pressure source** that is our heart. This process is known as ***bulk flow***. **Diffusion through membranes:** The rate at which a substance diffuses across a plasma membrane can be measured by monitoring the rate at which its intracellular concentration approaches diffusion equilibrium with its concentration in the extracellular fluid. To simplify, assume that because the volume of extracellular fluid is large, its solute concentration will remain essentially constant as the substance diffuses into the intracellular volume. When we talk about diffusion processes, the **net flux J** of material across the **membrane is from the region of higher concentration to the region of lower concentration**. ***Fick diffusion equation*** **J = P.A.(Co-Ci)** The numerical value of the permeability coefficient, P, is an experimentally determined number for a particular type of molecule at a given temperature. And it reflects the ease with which the molecule is able to move through a given membrane to make it easier. The greater the permeability coefficient, the larger the net flux across the membrane for any given concentration difference and membrane surface area. The major limiting factor of diffusion across this membrane is the hydrophobic interior of its lipid bilayers that you have to always, always remember that **oxygen, carbon dioxide, fatty acid, steroid hormones** are example of nonpolar molecules that diffuse rapidly through the lipid portion of the membrane. Lipophilic, lipid-loving substance move through this membrane very easily. Polar molecules or hydrophilic do not diffuse rapidly or easily through this membrane. **Diffusion through ion channels:** Sodium, potassium, chloride, calcium diffuse across plasma membrane at a much faster rate than would be predicted from their very low solubility in membrane lipids. Moreover, **different cells have quite different permeability to these ions** where **nonpolar substances have similar permeabilities in different cells**. The fact that artificial lipid bilayers containing no protein are practically impermeable to these ions indicate that the protein component of the membrane is the one responsible of this permeability differences. **[Membrane Potential]** The membrane potential provides an electrical force that influences the movement of ions across the membrane. **Even if there is no difference in ion concentration across the membrane, there is always a net movement of positive ions into the cells and negative ions out of the cell because of the membrane potential.** Consequently, the direction and magnitude of ion fluxes across membrane depends on both the concentration difference and the electrical difference. These two driving forces are known as the ***electrochemical gradient*** across membrane. Water is not expected to cross the membrane easily by simple diffusion. All cell membrane are permeable to water because of the presence of what we call water channels or aquaporin channels. **[Osmosis]** **Osmosis** is the net diffusion of water across a membrane. As with any diffusion process, there must be a concentration difference in order to produce a net flux. Now how a difference in water concentration can be established across a membrane? The addition of solutes to water gonna lower the concentration of water in the solution compared to the concentration of pure water. **The degree to which the water concentration is decreased is gonna be dependent upon the number of particles of solute in the solution and not upon the chemical nature of the solute.** Note that a molecule that ionizes in solution decreases the water concentration in proportion to the number of ions formed. Water is going to be distributed differently between the intracellular fluid and extracellular fluid. ***Important factor: Distribution of water between intracellular fluid (ICF) and extracellular fluid (ECF) is determined by distribution of solutes.*** *[The osmolality of the ICF and ECF at steady state are the same.]* ***'Osmolality'?* (amount of solute per Kg of solvent, typically water)** ***versus*** ***'Osmolarity'?* (amount of solute per Liter of solution), which is commonly measured** **(For dilute solutions or biological fluids, these 2 terms are nearly identical in numerical value. (Note that PLASMA is 93% WATER; the rest is solids \-- lipids and protein).** **Therefore, it is OK to use these terms interchangeably.** Osmolality of all body fluids compartment is maintained constant at around **300 milliosmol, this is per kilogram of water**. Intra and extracellular osmolality are equal at steady state because of the presence of aquaporin channels. **[Body Fluid Osmolality]** The osmolality of body fluids is determined by the ratio of total body osmotically active solute (TBS) to total body water (TBW): **TBS = total ECF solute + total ICF solute** **Also, since body fluid compartments are in osmotic equilibrium,** **Total body osmolality = Plasma osmolality** Because cell membranes are freely permeable to water, the distribution of total body water between the two major body fluid compartments is determined by the effective exchangeable solute content of the two compartments, therefore **osmolarity of the ECF is equal to the osmolarity of the ICF**, therefore the volume of the ECF is a function of the effective ECF solute content and the volume of the ICF is function of the ICF effective solute content. - **[Total body content of sodium] (along with the accompanying anions, Chloride and bicarbonate) is the primary determinant of [extracellular] fluid volume, and by extension intravascular (plasma) volume.** - **[Total body content of water] determines body fluid osmolality and therefore the volume of the [intracellular] space (cell volume).** **The volume of a body fluid compartment is determined by its effective solute content**. Na^+^ is relatively restricted to the ECF compartment. Moreover, Na^+^ (together with its accompanying anions, chloride and bicarbonate) is the major ECF effective solute. It follows, **therefore, that total body Na**^+^ **(or ECF Na**^+^ **content) is an important determinant of ECF volume.** Indeed, provided body fluid osmolality is maintained constant, *total body Na^+^ must be the major determinant of ECF volume*. Total body Na^+^, of course, is determined by the balance between Na^+^ intake and Na^+^ excretion (i.e., by Na^+^ balance). The total blood volume is typically about 5.5 liters, of which plasma volume is about 3 liters and blood cell volume is 2.5 liters. **One-fourth of the extracellular fluid is plasma and the rest is interstitial fluid. Therefore, one-twelfth of total body water content is in the plasma.** III. **Gain or Loss of Electrolyte-Free Water** 1. ***Case 1: When you add electrolyte-free water***, rarely it\'s gonna affect the circulating blood volume. Pure water excess, as might occur in someone who drinks more water than the kidney is able to excrete, it is associated with ICF and ECF volume expansion and with decreased body fluid tonicity **hypotonicity**. Under normal circumstances, the water load would be quickly excreted. The additional water is distributed throughout total body water with 2/3rd of the water excess located in the ICF and 1/3rd in the ECF. 2. ***Case 2: If we lose electrolyte-free water,*** this water electrolyte-free is gonna be associated with ICF and ECF volume contraction. This results in **hypertonicity**. So as I said, the water loss will come from both ICF and ECF, two-third of the loss is derived from the ICF, and one-third derived from the ECF. IV. **Gain or Loss of Iso-osmolar Saline Solution** 3. ***Case 3: NaCl fluid excess*** Isotonic fluid excess is associated with **ECF expansion**. ICF volume and body fluid osmolality are unchanged. If you add to a patient a given volume 1 liter of water containing isotonic solution of sodium. Sodium will not be able to enter into the intracellular space. Therefore it\'s gonna remain in the extracellular space, and the volume of the extracellular space will expand. We call the addition of a sodium chloride solution a **non-penetrating solution** because sodium is non-penetrating. What do I mean by non-penetrating? Because of the presence of the sodium ATPase pump that is active, because of the presence of the channels, sodium will enter in the extracellular fluid and go out back to the extracellular fluid. 4. **Case 4: NaCl fluid deficit** It will be lost from the extracellular space, water will leave as well causing contraction. The term electrolyte-free water that we use, this is a hypotonic fluid. It has lower tonicity than plasma. Isotonic fluid, such as 0.9% of sodium chloride or normal saline or muscle is one with an osmolality equal to that of body fluid, 300 in that case. Hypertonic fluid have higher osmolality than body fluid. ***Therefore, what happens when we lose sodium chloride or saline? Everything will be lost from the ECF. Therefore, the ECF volume will decrease, while ICF volume and body fluid osmolality are unchanged, because we\'re adding a solution.*** Substances that cannot cross the plasma membrane are called **non-penetrating solute**. They do not penetrate through the lipid bilayer. If you remember well, sodium and chloride are present particularly in the extracellular fluid. They diffuse into the cell through ion channels in the plasma membrane or enter the cells during what we call secondary active transport. You have seen that the plasma membrane contains sodium, potassium, ATPase pump that gonna move sodium out of the cells. Therefore sodium moves into cells and is pumped back out, behaving as if it never entered in the first place. Therefore extracellular sodium behaves as a non-penetrating solute. Any chloride ion that enters cells are also removed as quickly as they enter due to the electrical repulsion generated by the membrane potential and the action of secondary transporter like sodium. Inside the cells potassium is a major solute. Most of large porous molecules are unable to diffuse through the plasma membrane. Although potassium can diffuse out of the cells through potassium channel, they are actively transported back because of the sodium potassium ATPase pump. The net effect as with extracellular sodium and chloride is that **potassium behaves as if it was a non-penetrating solute**. Because water can diffuse across plasma membrane, water in the intracellular and extracellular fluid will come to diffusion equilibrium. Therefore, now you know why inside and outside osmolarity is the same. **Since the solution is isotonic, by definition the ECF osmolality does not change, and there is not an effective osmotic gradient across the cell membrane.** **Consequently, there is *no movement of water either into or out of the cells*, therefore the one liter will remain in the extracellular fluid with about one-fourth in the plasma volume, which is gonna increase.** V. **Addition of an Effective Solute** When glucose or any other osmotically active solute is added to the ECF compartment, in the absence of insulin, as you know, glucose is not transported into the cells and metabolized. Rather, it accumulates in the ECF. And being relatively restricted to this compartment, **it\'s going to act as an effective solute, drawing water out of the cells. ICF volume will decrease and ECF volume will increase.** **Tonicity determines cell volume:** ***Hypertonicity always implies a shift of water from ICF to the ECF (shrink). And hypotonicity always implies a shift of water from ECF to ICF (swell).*** - Isotonic solutions have the [same] concentration of *nonpenetrating* solutes as normal extracellular fluid. - Hypotonic solutions have a [lower] concentration of *nonpenetrating* solutes as normal extracellular fluid. - Hypertonic solutions have a [higher] concentration of *nonpenetrating* solutes as normal extracellular fluid. **Responses to cell swelling and shrinkage:** Summary: - Because cell membranes are freely permeable to water, the osmolalities of all body fluid compartments (ICF; and ECF which includes interstitial and plasma) are equal at steady state. - Body fluid osmolality is measured by plasma osmolality (P~Osm~) and it is determined by the [ratio] of total body osmotically active solute (TBS) to total body water (TBW). - A fairly good surrogate of P~Osm~ is P~Na~ (plasma sodium concentration). - Osmolality influences the distribution of water across the cell membrane and tends to determine cell volume (ICF volume). - Total body Na content, with the accompanying anions (present mainly in the ECF) determines the ECF volume