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Body Fluid Compartments

Chapter Reading:

Chapter 25 pages 292-301

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Lecture outlineI. Water compartments of the body

A.IntracellularB. Extracellular

i. Interstitialii. Plasmaiii. Transcellular

II. Compare/contrast water compartmentsA. SizeB. compositionC. Osmolality

III. How do we have different composition/ movement of solutesA. Different permeabilityB. Types of transport across the membrane for solutes--Protein transportersC. Review of Simple diffusion of solutes

IV. Movement of waterA. Osmosis-movement across cell membranes due to unequal particlesB. Hydrostatic pressure- movement across capillaries

V. Examples of when water vs. solute movesVI. Definition of osmotic pressure

A. Examples of osmotic pressure differences in body fluid compartmentsVII. Tonicity vs osmolality

A. Examples of tonicity and osmolality

• Why do you need to understand body fluid compartments and osmolarity calculations? Many of you will be applying IV care for patients, and sometimes doctors make mistakes, so you need to be able to catch these errors. Most medical solutions are calculated in units that don’t require a periodic table of elements, but if someone miscalculates a solution, and you inject it, and the patient crashes, you are just as liable, and you will be sued.

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Water

• Water makes up 45-75% of our body weight– 70 kg man X 0.60 = 42 kg

= 42 L– How much of your own

weight is water? 2.2lb/1kg

• Divide this into two compartments– Intracellular water– Extracellular water

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Compartments• Intracellular Fluid

(30-40% Body Wt)• Extracellular Fluid

– Interstitial fluid (the water immediately outside cells,

between and around cells) (16%)

– Plasma fluid (the water inside blood vessels, but not in

blood cells) (4-5%) – Transcellular fluid (the

water enclosed in chambers lined by epithelial

membranes) (1-3%)

These are stomach epithelial cells

Lumen of stomach

?

?

???

• If you manipulate one body fluid compartment, it has an effect on another compartment. Body fluid compartments have different sizes and volumes, and different compositions. What is dissolved in the fluid is different. It does not matter about size and composition…if you can count every particle in that compartment, in all the compartments you should get the same number of particles: 300 million particles per liter, expressed as “300 million osmoles” or “300 mili-osmoles”. It could also be described as having “an osmolarity of 300”.

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• That means that there are 300 million particles (or 300 milliosmoles, abbreviated 300 mOsm) of things in each compartment. If one compartment has more particles than another one next to it, and if those particles cannot reach equal numbers on their own because the cell membrane blocks their passage, water will try to dilute the compartment with the higher number of particles until they are at the same number of particles per liter. Water always moves across the compartments because cell membranes always allow water to pass.

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Body Fluids compartments

Different compositions (different amounts of individual particles)

Different volumes, Same osmolalities (total number of particles)

0.3 Osmolal = 300 mOsmolal (actually closer to 280mOsmolal)

IntracellularInterstitialPlasma

• If the plasma is diluted to 260 mOsm, and the cells next to a blood vessel are still at 300 mOsm, the cells now have more particles. What will move, in order to dilute the cells? Water. Why? Because particles suck! The cells will draw the water to it. Water will move from the plasma to the adjacent cells. What happens to the cells? They will lyse (rupture). When would that ever happen in real life? A contestant on a radio game show drank a lot of water for a week, and was not allowed to go to the bathroom much. She developed a headache, went home, and died. She was OVER hydrated, so the original 300 particles per liter in her plasma were now at 300 particles per 2 liters, since the excess water increased her blood volume. That means there were only 150 particles per liter, so overall, there were now fewer particles in the plasma than in the adjacent cells. Her brain cells sucked up the water until they ruptured and exploded in her skull.

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• Thus, we learn that if a person is over-hydrated, the plasma will be diluted below 300 mOsm, but the cells still have 300 mOsm in particles. So, the cells will draw in more water from the plasma and the cells will enlarge and rupture. Therefore, she should have been given an IV that was hypertonic (greater than 300 mOsm) to balance out the number of particles in the plasma so it matched the number of particles in the cells.

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• The opposite is true for someone who is dehydrated. Since the original number of particles was 300 million particles per liter, and then the patient became dehydrated, they would now have 300 million particles per half a liter (since they lost plasma volume due to dehydration), so their plasma is actually at 600 mOsm per liter. Therefore, if a patient is dehydrated, you will give an IV that was hypotonic (less than 300 mOsm, be careful of the drip rate) to balance out the number of particles per liter within the plasma and within the adjacent cells. If, a doctor accidentally tells you to give a dehydrated patient an IV solution that is hypertonic (greater than 300mOsm), the plasma will have more particles than the cells, and the cells will have the water sucked out of them, which also causes death. Understanding body fluid compartments is important!

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• There are 100 trillion cells in your body, 25% of them are RBCs. Dead RBCs are the reason why your pee is yellow and your poop is brown! You will understand why, later in the semester.

• About 50% of your body weight is from water. How can you calculate your water weight? For every 2.2 pounds, you are 1 kg in weight. Then multiply that number by 0.6 to see how much water is in your body.

• Water makes up 45-75% of our body weight– 70 kg man X 0.60 = 42 kg = 42 L of water is in his body– How much of your own weight is water? 2.2lb/1kg

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• The total amount of water in your body is divided into two compartments– Intracellular water is inside of your cells. Most of your water

is here.– Extracellular water is outside of your cells. There are three

types.• Interstitial fluid (the water immediately outside cells,

between and around cells) (16%)• Plasma fluid (the water inside blood vessels, but not in

blood cells) (4-5%) • Transcellular fluid (the water enclosed in chambers lined

by epithelial membranes, including the GI tract and synovial joints) (1-3%)

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• All compartments are not the same size. Which is the biggest? Intracellular

• What’s the smallest? Trancellular• The inside of each cell is low sodium, low in

free calcium, high in potassium, high in proteins (there are four times as many proteins in cells than there are in plasma).

• Outside of cells (in the plasma) are high in sodium and free calcium, low in potassium and proteins.

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Different compositions across the membrane: How can this be?

• As stated, if you could count all the solutes (particles) inside and outside of the cell, they are the same number (300 mOsm). Why does it need to be that way?

• All particles pull water to them, whether the particle is glucose, calcium, a protein, salt, etc. We don’t want a net gain or loss of fluid across the cell membrane or the cell will shrink or burst. Not all compartments have the same volume liquid, but they all have the same number of particles per liter.

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• If the numbers of particles are always the same, how can we have higher numbers of potassium ions inside of the cell compared to the outside of the cell? Won’t the potassium ions want to move down their concentration gradient towards equilibrium? Yes, they will want to, but the cell membranes are semi-permeable and will prevent the potassium (and other particles) from crossing.

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• If you have a cell containing 300 mOsm of potassium (K+) immersed in pure water, will it shrink or burst? The potassium cannot flow out of the cell to equalize its numbers inside and outside of the cell because it is blocked in by the cell membrane. That means there are more particles on the inside of the cell than in the pure water it is soaking in. The particles in the cell will suck water into the cell until the cell bursts. In theory, if the substance we are talking about was a particle other than potassium, and one that can cross the cell membrane whenever it wants to, it would simply diffuse across the cell membrane until it reached equilibrium, so the cell would not burst.

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• What particles can cross the cell membrane?

• Gases (O2, CO2)

• Lipids and lipid-loving (hydrophobic or lipophylic) substances, such as alcohol

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Functions of Membrane- Selective Permeability and Transport

• Selectively permeable- allows some substances to pass between intracellular and extracellular fluids

• Only small uncharged molecules or fat soluble molecules can pass through membrane without help- diffusion (passive transport)

• Facilitated diffusion (still passive transport)

• Active transport

http://www.northland.cc.mn.us/biology/BIOLOGY1111/animations/active1.swf

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Membrane Function• Passive transport

includes diffusion across a membrane– diffusion is tendency of

molecules to spread out spontaneously from area of high concentration to area of low concentration

• at equilibrium molecules diffuse back and forth-no net gain or loss

http://www.northland.cc.mn.us/biology/BIOLOGY1111/animations/active1.swf

This only happens if the solute is permeable across the cell membrane!

• If movement across the cell membrane does not require energy to be spent, the movement is called passive transport. There are two kinds of passive transport: simple diffusion and facilitated diffusion. If movement across the cell membrane requires energy to be spent, the movement is called active transport. The energy molecule that is spent is called ATP.

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• A water-loving (hydrophilic) substance needs a special channel in the cell membrane to cross, and it will cross the cell membrane either by simple diffusion (no ATP required), or it may need a transport protein to carry it into or out of the cell by one of two processes: facilitative diffusion (no ATP required) or active transport (ATP is required).

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• Facilitated diffusion is when an ion wants to travel down its concentration gradient, but there is a channel in the cell membrane that opens and closes by a protein which enlarges or shrinks to open or block the channel (remember, this is still passive transport, so it does not need ATP).

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• Active Transport is when a substance needs to move against its concentration gradient (it is moved from an area of low concentration on one side of the cell membrane to an area of high concentration on the other side of the cell membrane). It accomplishes this because a protein embedded in the cell membrane grabs onto the substance and drags it across the cell membrane (this requires ATP).

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• Passive Transport:• Simple Diffusion

Facilitated Diffusion

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How does water move?

• Two ways:

• Osmosis

• Hydrostatic pressure

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Movement of water• Always passive and unsaturable• Pores (aquaporins) serve as conduits

(ubiquitous AQP1 vs. collecting duct AQP2)• Osmosis

– a chemical potential energy difference dependent on the water concentration on two sides of the membrane

– Easier for physiologists to measure the solute concentration (more solute means less water; less solute means more water)

– Driving force for water movement across cell membranes

• Hydrostatic pressure– The pressure of the fluid exerted on the

vessels, or container (change in energy/mole)

– Animal cell membranes are “flexible” so it is not a driving force across cell membranes

– IT IS a driving force for moving plasma water across walls of capillaries

If you squeezed on this bottle to get the water to shoot out, what kind of pressure would this simulate?

Hydrostatic Pressure

• Squeeze a water bottle to shoot the water out, this is hydrostatic pressure. Hydrostatic pressure is the pressure of the water exerting on the vessel wall. If you push harder, the water will shoot farther. The hydrostatic pressure of water being filled in a balloon will exceed the capacity of the balloon and pop. That is how water moves between cells and into cells so that plasma becomes interstitial fluid. The plasma leaks out between the endothelium of the capillaries. If you have a swollen ankle and apply an ace wrap, you are applying hydrostatic pressure to force interstitial fluid back into the plasma. Hydrostatic pressure is not the movement across a cell membrane. That is osmosis.

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Osmosis

• Osmosis is movement of water across the cell membrane because of the particle different on each side. Osmotic pressure can be measured. If there is more water on one side of a membrane than the other side of the membrane, the water will move down its concentration gradient, which is the same condition of moving from low particles to high particles.

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• Dialysis tubing is used in laboratory demonstrations about osmosis because it is not permeable to glucose but water can cross it. It helps you learn about the body because glucose also cannot get across the body’s cell membranes, but water can. In a laboratory demonstration, water will move into the tubing until it reaches a certain column height. It does not continue to climb higher and higher in the column indefinitely, because gravity will be exerting forces on it too. Eventually, the water will reach a certain height and then stop. The point at which is does this is when the hydrostatic pressure caused of the gravity is equal to the osmotic pressure of the water trying to get into the tube. If we did this experiment in outer space, all of the water would cross over the membrane and the column would rise until all the water is gone.

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• Imagine that you take some aspirin and wash it down with water. If the aspirin particles can get across the cell membrane, there will be no net gain or loss of water in the compartment.

• But if you eat a bunch of cellulose (fiber), it cannot cross a cell membrane. There will be more particles in the GI tract lumen, so the GI lumen will suck water from the nearby cells into the intestinal lumen. That is how laxatives work! They will extract fluid from the body and in excess, they may cause dehydration.

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• Osmotic pressure is the amount of hydrostatic pressure required to stop osmosis from moving water from low to high concentration across a cell membrane. Osmotic pressure is attributed to the osmolarity of a solution. The solution with the highest number of particles will have the highest hydrostatic pressure.

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Membrane Function

• Osmosis is movement of water to an area with more solute– if cell membrane

permeable to water but not solute

– direction of osmosis is determined by differences in total solute concentrations

– Hypo-osmotic– Hyper-osmotic– Water always moves!

Watch your body fluid compartments

http://student.ccbcmd.edu/~gkaiser/MYANIMATIONS.pdf

When would this stop?What if we were in space?

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Review: Implications of Concentration and Osmolality Differences Across Membranes

• First, let’s focus on a solute that can move across the membrane.

• Let’s say these green particles are aspirin molecules in the stomach.

• How would these molecules move across the body fluid compartments?

• Diffusion-random movement of particles from “high to low”

http://www.indiana.edu/~phys215/lecture/lecnotes/diff.html

Plasma GI tract

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Review: Implications of Concentration and Osmolality Differences Across Membranes

• Now, let’s say you’ve eaten fiber (cellulose)

• You can’t absorb it!• There are more

particles in one body fluid compartment

• What will happen?• Water movement

– Osmosis– Hydrostatic

pressure

http://www.indiana.edu/~phys215/lecture/lecnotes/diff.html

This is the basis for how diuretics and laxatives work!

Plasma GI tract

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Osmotic Pressure

• Osmosis occurs when water moves from a solution w/ fewer particles to one with more particles because the particles can’t move across the membrane!– Remember “particles suck (....in water).”

• osmotic pressure is the amount of pressure required to stop osmosis from happening (hydrostatic pressure).

• Water is likely to enter a solution that contains lots of particles that are impermeable across a membrane– thus the solution is said to have a high osmotic pressure!

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Osmotic Pressure:the amount of hydrostatic pressure (force of fluid exerted on the vessel wall) required to counter osmosis

Osmotic pressure is attributed to the osmolarityof a solution

Figure 4-10;Guyton & Hall

Isosmotic - has same osmolarity as body fluids

Hyperosmotic - higher osmolarity than body fluids

Hyposmotic- lower osmolarity than body fluids

• In a U-shaped tube separated by a membrane, water moves to the side with more particles (Particles suck). If a compartment has a high number of particles, there is a low amount of water there, so water will move from there to the area with fewer particles. Scientists can count how many particles there are in a solution. If a membrane prevents the particles from moving down their concentration gradient, water will move from low concentration (low particles) to high particles. Osmotic pressure is the amount of hydrostatic pressure you need to apply to stop the water from moving (from the top of the tube where the particles are highest). PhysioEx has an osmosis activity. Set up two beakers, one with high and one with low particles, apply a force to the top of the high particle beaker, and measure how much force is needed to push it down until there is no net gain or loss of fluid on the side that has a lot of particles.

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• What will happen to a cell placed in the following solutions?

• Isosmotic (300 mOsm): no net gain or loss of water.

• Hyperosmotic (600 mOsm): particles suck, so solution will suck the water from the cell, which will shrink.

• Hyposmotic (100 mOsm): particles suck, so cell will suck water from the solution and burst.

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• The above example assumes that the particles in the cell cannot diffuse out, which is usually the case.

• However, there are particles (such as urea) that can cross a membrane. Urea will diffuse out of one compartment and into another, down its concentration gradient. As it does so, water will also be diffusing back and forth down its own concentration gradient. In this case, although the water will go back and forth while it is seeking equilibrium, there is no net gain or loss of water from each compartment. The solute (urea) will diffuse quickly. There are only transient changes in water if a particle is diffusing across a membrane.

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Example with Diabetes• Increased sugar in the blood

• Relatively less water due to increased solute concentration

• Describe the movement of water when the mOsmolal changes!

intercellular

Plasma(extracellular)

Transcellular(extracellular)

Interstitial(extracellular)

S

S

S

S

S300

Water flow

G.I.Tract

304mOsm

Example with Diabetes

• When you eat, sugars are absorbed into plasma. Normally, insulin transports these sugars into the cells, but in a diabetic with no insulin, the sugars stay in high concentration in the plasma. That raises the plasma above 300 mOsm, while the interstitial fluid is still at 300. Where will water go? Water will move from the interstitial fluid into the plasma. Now, the interstitial space has less water, but the same number of particles, so it may be at 300 particles per HALF a liter, instead of 300 particles per liter. To calculate the number of particles per liter, multiply by 2 and you will see that the interstitial space has actually become 600 mOsm.

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• The interstitial space now has more particles than the intercellular area next to it. Water will then go from the cells into the interstitial space (which gets the water sucked out of it again from the high plasma osmolality), and the person gets dehydrated. Diabetics have excess sugar circulating in the plasma, and the kidneys cannot filter all of it, so the sugar builds up in the nephron lumen. Water from the capillaries is drawn into the nephron lumen (higher mOsm), so more urine is produced. Sugar will also spill into the urine and can be detected in a urinalysis (UA).

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• When a person becomes dehydrated, it triggers the brain to release anti-diuretic hormone (ADH), which stimulates the thirst center in the brain, encouraging the person to drink more water. The condition where a person drinks a lot of water because they are thirsty is called polydipsea, and is characteristic of a person with diabetes.

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Test yourself- by picking which one of these is correct

• What happens with diabetes mellitus?a) Cells lose water to ECF via osmosis; ECF osmotic

pressure rises; Solute concentrations increase in ECF.

b) Solute concentrations increase in ECF; Cells lose water to ECF via osmosis; ECF osmotic pressure rises;

c) Water is lost from the ECF; Solute concentrations increase in ECF; ECF osmotic pressure rises; Cells lose water to ECF via osmosis.

d) Solute concentrations increase in ECF; ECF osmotic pressure rises; cells lose water to ECF via osmosis

What if the question described an athlete who was dehydrated?

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Note this poor child’s swollen distended belly.

How does that relate to her lack of dietary protein?

Used with permission given by A. Imholtzhttp://academic.pg.cc.md.us/~aimholtz/

Kwashiorkor- “disease of deposed child” (no longer suckled).•Corn has no tryptophan•Economically disadvantaged countries that use cornmeal•Hospitals and nursing homes, too!•Failure to grow•Lethargy•Depressed mentality•Edema caused by.......Low plasma protein. So, the fluid moves into the interstitial

space (seemingly increased conc) and then into an area of low resistance—the peritoneal cavity

Example with Malnourishment

• We need all of our essential amino acids, and problems can occur if you are deficient in only one amino acid. All compartments, including the plasma, should be 300 mOsm. There are many plasma proteins; the most abundant is albumin, which is made in the liver. If your diet is deficient in an amino acid, the liver cannot make enough plasma proteins. If albumin numbers decline, particles in the plasma decrease. Plasma is now 200 mOsm. Other compartments will suck the water from the plasma and edema will result. Therefore, lack of dietary protein causes a low mOsm in the blood plasma. Since there are more particles in the interstitial space, water will move from the plasma to the interstitial compartment.

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• The peritoneal cavity is an area of low resistance; there is not much there to hold back something that is pressing from the inside. The fluid goes from the plasma into the peritoneal compartment, and the belly becomes distended with fluid (ascites). It is not to be confused with a full stomach; ascites is characteristic of malnutrition and other diseases. Edema (excess interstitial fluid) also occurs in legs, since there is no pressure there to keep it in. Ascites is not just a problem of poor countries. Other people who often get ascites are alcoholics and the elderly who don’t eat their protein.

• When malnourished, the body will break down the proteins in the muscles to get what is needed elsewhere. Alcoholics drink their diet; the liver becomes so scarred that it can’t make proteins.

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Acites

• Ascites puts pressure on the bile duct (called portal hypertension), preventing the release of bilirubin, so this yellow pigment enters the tissues, turning the skin yellow, especially the white parts of the eyes. This yellow appearance of the skin is called jaundice. When excess bilirubin enters the brain, it causes nerve cell death. This is why alcoholics still seem drunk when they are sober. Bilirubin is the result of RBC death. Parts of the RBC can be recycled (such as the iron), but the bilirubin (part of hemoglobin) needs to be eliminated. Bilirubin is what causes the color of urine and feces.

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Our book refers to tonicity more than osmolality....are they interchangeable?

• NO!!!!!!!• Tonicity refers to whether a

solution will cause changes in cell volume (effective osmolality—that means, not permeable)

• Osmolality refers to the number of particles- regardless of permeability

• Is the solute an effective (impermeant) or ineffective (permeant) osmole?

• Some solutes (primarily urea) are freely permeable to cell membranes (exhibit passive transport). A hyperosmotic solution may cause only transient shifts in the body under steady-state conditions.

Figure 25-5; Guyton and Hall

Tonicity vs. Osmolality

• Tonicity and osmolality are not the same word. Tonicity refers to the number of particles in 1kg of water. Will there be a shift of water across the cell membrane? Most of the time, particles don’t move so the water does. If this was always the case, tonicity and osmolality are the same number. But substances, such as urea, can move across a cell membrane, so there is only a transient shift in water. In these cases, the resulting osmolality and tonicity are different.

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For example:

• 300mmol/L sucrose

• isosmotic to our bodily fluids!

300mmol/Kg sucrose

300mmol/kg sucrose is also isotonic- no change in cell volumeIt’s osmolality is also its effective osmolality (tonicity).

• Place a cell in isotonic solution: There are equal particles and no net gain or loss of water.

• This solution is considered to be Isotonic and isosmotic.

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What about 600mOsmolal Sucrose?

•Hyper-osmotic•Hypertonic

• Place a cell in hypertonic solution: The cell will shrink.

• This solution is hypertonic and hyperosmotic.

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• Place a cell in hyposmotic solution: The cell will swell

• This solution is hypotonic and hyposmotic.

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Let’s see what happens with urea

400mmol/Kg urea

Hyper-osmoticIsotonic (long-term)

• But place a cell in a solution with 400 mOsm of urea. The urea will move into the cell until it equalizes.

• The water will transiently shift from the solution to the cell until it equalizes, with no net gain or loss of water from the cell. The cell will not shrink, nor will it swell.

• This solution is isotonic but hyperosmotic.• Urea is important for proper kidney function, so it

needs to be able to cross a membrane. That’s why you can make concentrated urine.

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Study Tip:

• How to remember what a cell does in hypertonic water?• Hypertonic has an “e” in it. Make the letter e with your

body. See how you have to curl up and shrink to make this letter? A cell will curl up and shrink in hypertonic solution.

• How to remember what a cell does in hyportonic water?• Hyportonic has an “o” in it. Make the letter o with your

arms over your head. See how you have made yourself bigger? A cell will swell up in hyportonic solution.

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