S2 Physiology Unit 2 - Body Fluid Physiology
Where is the majority of potassium stored? what are the 2 channels found on these cells that help facilitate the movement of potassium? what are the 4 things that promote the movement of potassium into the cell? what are the 4 things that promote the movement of potassium out of the cell?
We are now going to talk a little more about the regulation of potassium. We just talked about how potassium was the major ion and regulator of our extracellular fluid. At some point in the past, we have learned about the Nernst equation and about how potassium sets the resting membrane potential of a neuron. Basically, what is going to determine the concentration of potassium in the ICF versus the ECF is going to be the factors that control its movement. When we discussed the Nerst equation last semester, we talked about the idea that there are potassium channels that are just open and that it can freely flow inside and outside of the cell. But in muscle cells, we also have additional points in control. So this figure in particular is most useful when we are thinking about skeletal muscle. Although sometimes it will apply in certain cases to things like the collecting duct. The first thing you need to know is that potassium is stored in skeletal muscle as a way to help dampen plasma potassium levels. We will see an example of this in the next NC. Furthermore, muscle cells have a potassium hydrogen exchanger and a sodium-potassium pump. Therefore, anytime we are pumping out sodium we can bring in potassium. This is one mechanism by which we can bring potassium into the cell. The other mechanism is the potassium hydrogen exchanger which works in a similar way. If potassium is in abundance outside the cell it will travel inside the cell through this exchanger and we will secrete hydrogen ions on into the ECF. If we have free hydrogen ions in abundance out in the ECF we are going to absorb them into the skeletal muscle and secrete potassium out of the cell. There are a few factors that are clinically useful to remember that help push potassium into muscle cells. 1. insulin 2. β αgonist 3. aldosterone 4. alkalosis insulin and β agonist are typically given if we have a pt with hyperkalemia. Aldosterone also helps push potassium into the muscle cell. Remember that one of the things that regulates aldosterone is hyperkalemia. And lastly, alkalosis also does this. This is because we would have a lower hydrogen ion concentration than normal in the ECF therefore we would not be bringing hydrogen ions into the skeletal muscle cell considering it is not in abundance outside of the cell. Therefore, in alkalosis, we want hydrogen ions in the ECF, not in the skeletal muscle. SO, the skeletal muscle will secrete those hydrogen ions out and bring in potassium. If you want potassium to shift out of the cell we also have a couple of different options. 1. hyperosmolarity 2. exercise 3. cell lysis 4. acidosis If you want potassium to shift out of the cell we also have a couple of different options. We can create hyperosmolarity. What this means is we can increase the osmolarity out in the extracellular fluid. This will draw water out of the cell and as that water leaves potassium tends to follow. Furthermore, exercise or something equivalent like malignant hyperthermia where you are experiencing contraction of a muscle. When you contract the muscle, you have depolarized it, therefore, as sodium comes into the cell, we release potassium out of the cell. Hense, exercise or MH tends to have the effect of pushing potassium out of the cell. Cell lysis can also lead to potassium leaving the cell. This could be seen in a crush injury or very extreme exercise that causes rhabdomyolysis. where we are basically rupturing the cell membrane of the cell and the potassium is leaking out. The last one is acidosis. With acidosis we are going to have a higher concentration of hydrogen ions outside of the muscle cell in the ECF, therefore it will travel into the muscle cell and potassium will leave. The big thing for quizzes and exams is remembering what things are going to push potassium in versus what things are going to push potassium out.
What are the two components of extracellular fluid? how do we determine this volumes? how can we calculate total blood volume?
As we discussed earlier, the ECF is composed of both the interstitial fluid and plasma. Interstitial fluid The interstitial fluid volume is generally about 3/4th of the ECF volume. Like the intracellular fluid, the interstitial fluid does not really have any marker that can be used to determine its volume. Therefore, we use markers to determine the plasma volume and the ECF volume to calculate the interstitial volume. Intravascular plasma The plasma volume is about 1/4th of the ECF volume. There are 2 markers that can be used to determine the plasma volume - radioactive labeled albumin and then Evens Blue dye which is basically too small to move across a normal healthy capillary membrane. Total blood volume The last thing is the total blood volume. if you want to know what the total blood volume is and not just the plasma volume, you would need to know the plasma volume and then divide that by 1 minus the Hct. If you don't know the hematocrit just use 50% and that will get you pretty close. There will be questions over calculating each one of these factors. TWB, ICF volume, etc as well as total blood volume.
What are colloids composed of? what affect do they have in the body? what is the main difference between crystalloids and colloids?
Colloids on the other hand are generally water solutions that contain either proteins or other macromolecules such as starch or large molecules. Basically the more starch or the more molecules you have the greater the colloid oncotic force. so technically if you gave someone plasma that would be a colloid considering it has proteins in it. When giving colloids we are trying to increase the oncotic pressure for volume replacement. The increase in oncotic pressure will pull water out of the ICF and into the ECF. The main difference between colloids and crystalloids is that colloids last longer as the proteins and starches take a lot longer to break down and when it takes a lot longer to break down that means they are going to have their effect for a long period of time. Therefore, if we make a mistake and give too much fluid of isotonic saline it is really not that big of an issue or medical error. Eventually, the pt will pee out the additional fluid within the next few hours and the problem will eventually resolve itself. BUT if we give a pt too much colloids, those plasma proteins are going to be around for hours to days, depending on the specific colloid molecule that was in place, and it will have a longer more impactful effect depending on the current state of the patient. SO for short-term fixes of pressure, we use crystalloids but for long-term control of fluid management, we use colloids.
Hormonal defense of ECF volume and mOsm - what two hormones are involved and what are their roles?
Hormonal defense of ECF volume and mOsm AVP/ADH (Agrinine Vasopressin/Anti-Diuretic Hormone) is released from the posterior pituitary in response to increased blood Osm. It's major (but not only) renal effects are to reabsorb larger amounts of water from the renal collecting ducts. This dampens increases in plasma Osm. RAAS is activated in response to losses of plasma volume. It's major renal effects are to reabsorb Na+ in the renal tubules. Because water follows Na+, this will dampen the loss of plasma volume. The image basically re-emphasizes this principle between the hormonal systems. RAAS is principally concerned with helping reabsorbs sodium and water will follow so that the fluid that we reabsorb is isotonic. ADH because it increases urea reabsorption tends to only focus on water reabsorption therefore it tends to bring back more of a hypotonic volume. ADH does have some effect on sodium reabsorption which happens in the thick ascending limb of the loop of Henle on the level of the principal cells. We get more ENaC channels we get more add channels, aquaporin channels, and Na/K pumps in the principal cells. But in the collecting duct, principally in that medullary collecting back, we get lots of urea reabsorption. SO in general ADH is best suited for responding to changes in plasma osmolality, whereas RAAS is best suited for changes in ECF volume. If that volume loss is large enough we recruited ADH but we're talking at least greater than 10% volume on the loss before ADH becomes a significant contributor. YOU NEED TO UNDERSTAND THIS CONCEPT. IT WILL BE ON THE EXAM.
Is the concentration of ions the same in the interstitial fluid and plasma? If not, how are they different? what is the Gibbs-Donnan effect?
ICF is high in K+, Mg++, Pro, and HPO4. K+ is an important determiner of ICF tonicity and volume. ECF is high in Na+, Ca++, Cl-, and HCO3-. Na+ is an important determiner of ECF tonicity and volume. Plasma has higher Pro ("-"charged), thus charged particles don't distribute evenly (Gibbs-Donnan Effect) In the ECF you can see that sodium, calcium, chloride, and bicarb are all very high. The ion that is going to control the tonicity of the extracellular fluid the most is sodium considering it is in the highest concentration. You could argue that it is sodium and chloride considering they tend to bind one another. Bicarb is the most abundant base, this is the most abundant anion. it is handly to know what a normal bicarb is 24 mOsm. There are also more proteins in the plasma than in the interstitial fluid. We will talk about why that is later in the lecture. But other than that, for the most part, all of the other things look the same between the plasma and the interstitial fluid. The biggest difference you are going to notice is that the plasma tends to have more positive ions and the interstitial fluid tends to have more anions. If you think about this from the standpoint of the fact that these numbers are concentrations (molar equivalents per liter) and we are dealing with water being able to move freely across capillary membranes, how do we get these charge differences? How do we get more negatively charged anions in the interstitial fluid but more positively charged cations in the plasma? The answer to this comes down to the increase in proteins in the plasma. Most of the proteins are going to be too large to cross the capillary membrane and they are negatively charged. SO those negatively charged proteins in the plasma actually repel some of the anions from the interstitial fluid from moving over to the plasma side. Furthermore, since we have the negatively-charged proteins on the plasma side, it actually draws more cations into the plasma. This is known as the Gibbs-Donnan effect. The Gibbs-Donnan effect basically states that if you have charged particles that do not distribute evenly across the semipermeable membrane, which would be our capillary bed in this case, then there has to be something that can't move evenly. And that something, in this case, is going to be our proteins. Therefore, this is why we get a slight just a slight difference in the distribution of the cations and anions in the interstitial fluid and plasma.
KEY POINTS
Most of the body consists of fluid compartments divided into the intracellular fluid (ICF, all the cytosolic volumes collectively) and the extracellular fluid (ECF), consisting mostly of interstitial fluid and blood plasma. Total body osmolality is directly proportional to the total body sodium plus the total body potassium divided by the total body water. Na+ makes up the majority of the ECF tonicity and thus, is the most important determinant of ECF volume. K+ makes up the majority of the ICF tonicity and thus, is the most important determinant of ICF volume. Crystalloids contain water and electrolytes and may be isotonic, hypertonic, or hypotonic salt solutions. Colloids contain macromolecules dispersed in a solvent to draw water into the vascular space. Because they are large, they are harder to remove via the kidney and have longer lasting effects than crystalloids. Changes in the osmolality of the body fluids occur when a disproportion exists between the amount of these electrolytes and the amount of water ingested or lost from the body. The amount of water that enters a cell or compartment is related to the differences in tonicity. The measurement of body fluid volumes is accomplished by using compartment specific indicators and the Indicator Dilution Principle. Selection of IV fluids with the proper tonicity is critical to managing shifts in fluid/electrolyte balance. ADH is a powerful regulator of body water, and as such can influence water volume, tonicity and systemic blood pressure. RAAS is a powerful regulator of Na+, and thus can influence water reabsorption, volume and blood pressure. Hyperkalemia can form quickly given the narrow physiological range. Insulin, epi, and aldosterone can help force K+ into skeletal muscle cells in a crisis.
What 3 hormones are released when there is an increased plasmas potassium concentration? what are the effects of these 3 hormones? how does our body handle an increased potassium load?
Skeletal muscle dampens an imposed K+ load Increased plasma [K+] triggers a hormonal response including insulin, Epi, and Aldosterone which help increase the expression of the Na+/K+ to help transfer more K+ inside muscle cells. This sequestration of K+ allows time for the kidneys to excrete excess K+ without the threat of hyperkalemia. This is a direct action of potassium and does not involve the renin-angiotensin system. When you ingest a meal such as whole foods, potassium is going to increase pretty high. For example, if you eat an avocado that has roughly 1000 mg of potassium per avocado. When that potassium dumps into the plasma, it could easily get us to a range of low-level hyperkalemia. Therefore, we need a way to buffer these potassium loads that come from dietary sources. This is one of the roles of skeletal muscle. Skeletal muscle is a storage site for glucose which is what we focused on in the endocrine unit. From this standpoint, it is also the primary storage site of potassium. Looking at the diagram. As the blood potassium levels start to go up, two things occur - the β cells in the pancreas release insulin, and the adrenal gland releases epinephrine and aldosterone. When the pancreas β cells detect an increase in plasma potassium concentration they release a little bit of insulin. Nothing as high as what you would see with a high glucose meal but a little bit of insulin. This increases the expression of the sodium-potassium pump. A change in the plasma potassium also affects the adrenal gland. The medulla will actually produce epinephrine, which will also help increase the expression of sodium-potassium pumps in skeletal muscle. And then aldosterone also does the same thing. It is important to remember that the response of aldosterone to increased plasma potassium is NOT RAAS mediated. The increased plasma potassium ITSELF is causing the release of aldosterone. If it was RAAS mediated we would see an increase in renin and ANGII. but that does not happen in this case. we are just secreting more aldosterone. (looking at the graph) when we get this slight rise in our plasma potassium you will notice that we also get an increase in the uptake of potassium inside skeletal muscle cells. This allows time for the kidneys to get rid of that excess potassium. If we eat excess sodium, we can lower renin which will make our ANGII and aldosterone levels fall so that we do not reabsorb as much sodium. Any additional spik that remains after we can handle with ADH by diluting out any tonic effect that the additional sodium might have. On the other hand, with potassium, we have to find a place to store it so that we can give the kidneys a long enough time to excrete the additional potassium. Skeletal muscles are the principal site for this. Therefore, when looking at the yellow line we can see that potassium is moving into cells. It is going to move into most of our electrical cells such as neurons and cardiac cells but the vast majority is going to move into the skeletal muscle cells. What will happen is over time the potassium will basically start leaking out of the skeletal muscles. But that is given us enough time for the kidneys to be able to start its excretion process. Therefore, over the course of a day basically, any potassium load that has been absorbed by the muscle will eventually be leaked out and our kidneys as we filter the blood several times a day are going to excrete that excess potassium.
The kidneys regulate body fluid volume and composition by controlling ECF.
Step 1. What happens to the volume in the ECF compartment (ECF is the smaller compartment)? Step 2. What happens to the in the mOsm of the ECF compartment (ECF is the smaller compartment) Step 3. What happens to the volume and osmolality of the ICF? This is the diagram we will be using to describe how fluid compartments are going to change. We are going to walk through an example together. In these diagrams, the x-axis is representing volume. In this image, we are saying that the ECF is 14L and the ICF is 24L. The y-axis is showing osmolarity. The questions will give you some sort of starting state, therefore you will be given a scenario and be asked how it will affect the black box. The point of the black box is basically to say "this is where we are at homeostasis and how is this going to change based on the given scenario?" You will then draw a box to show how it has changed using dotted lines. In order to do that appropriately, you just need to follow the 3 steps above. SO the first thing is to ask yourself - what is going to happen to the volume in the ECF? You should always start with the volume considering if you are giving isotonic saline we know that it will not change the tonicity, therefore, all you have to do is increase the volume on the ECF side to represent that change. In the image, you can see what the diagram would look like if we gave someone isotonic saline. The ECF volume would increase BUT the tonicity/osmolarity does not change considering it was isotonic saline. Therefore, there are no changes on the y-axis. This would show the total effect of this scenario. SO always start with the ECF volume. The second thing you should ask yourself is - what is going to happen to the osmolarity of the ECF? If we gave hypertonic saline or hypotonic saline? it would change the tonicity of the ECF which will change the fluid movement either into or out of the ICF. Lastly, you should go through the first two steps again with regard to the ICF. SO what is going to happen to the ECF volume? ECF osmolarity? then once those changes have happened what is going to happen to the ICF volume? ICF osmolarity?. In the end, you should be able to draw one box to show what is going on. THIS WILL BE ON THE EXAM
What is the relationship between the extracellular fluid volume and blood volume? For example, what happens when we increase our extracellular fluid volume? what happens if we decrease our extracellular fluid volume?
The graph is showing the relationship between extracellular fluid volume and blood volume. It is basically accounting for one of the two components that makes up the extracellular fluid volume. If we have an increase in our ECF, our blood volume will go up a little bit which is where hypertension comes from. But, at a certain point, the capillary hydrostatic pressure gets so high in the vasculature that fluid will begin to be pushed into the interstitial fluid. This is where the pitting edema comes from and it is not associated with long healthy lives considering eventually that edema will prevent gas exchange in the worst scenario. if we go the other way and decrease our extracellular fluid volume to a point where we cannot maintain the blood volume the endpoint would be death.
What 2 systems play an important part in regulating ECFV and osmolality? where do most volume disturbances originate in? what would an increase in sodium cause in terms of the ECF osmolarity? what changes would occur because of this?
The kidney's and endocrine system play an important part in regulating ECFV and osmolality. 1. Typically most volume disturbances originate in the ECF! 2. Therefore, the kidneys regulate body fluid volume and composition by controlling ECF. An increase in Na+ intake would drive up the ECF mOsm. Thirst and ECF fluid shifts would buffer this increase, and the kidney would have to excrete Na+ and water to restore homeostasis. We are now going to link what we learned about renal function to the body fluid compartments considering it is the job of the kidneys to basically control the ECF volume and osmolarity. And it controls the volume of the ECF by controlling the osmolarity. Looking at the top graph, we are going to look at an example of this. The dotted line is representing our intake but this also represents excretion. In this graph, we only have one dotted line, therefore which means that our intake matches our excretion and the pt is in a steady state. They are matched. Whatever we are bringing in we are going to be urinating out to maintain the extracellular fluid volume. If this weekend you're getting stressed and start eating a lot of simple carbohydrates full of salt, the intake of sodium is going to skyrocket. If you continue eating this high sodium diet, we can assume you might have some sodium retention. The sodium retention is going to reflect what you took in minus what we were able to excrete. We know that the kidneys are a slow system, therefore it is very easy to take in salt faster than the kidneys can excrete it. When this occurs, the expression line is going to plateau when it reaches equilibrium with your intake line. Whatever the difference is between the splay of those two lines (which is represented in pink) is our sodium retention in this case. If you look at the bottom graph, you can see that this occurs the extracellular fluid volume increases a little bit. It does not increase as much as you might think considering we are only retaining enough additional water to buffer the sodium retention. Why do we have to bring in water to buffer the sodium retention? How do we buffer this sodium retention? The higher the concentration of sodium, the more water will want to move towards it. Therefore, we will get a shift of fluid from the ICF to the ECF to decrease the osmolarity of the ECF. We also would inhibit RAAS in this case, as we would not want to retain any additional sodium. Therefore, we would decrease renin which would lower ANGII and aldosterone. Furthermore, when an individual consumes excess sodium it tends to make the individual thirty. therefore they are also going to consume more water in this sodium retention state. Lastly, we would increase ADH so that we can retain more water to help dilute the additional sodium. Therefore, during the state of sodium retention, we would expect low RAAS, ANGII, and aldosterone. High ADH. And fluid movement from the ICF to the ECF. These changes are basically what is causing the increase in the extracellular fluid volume. Is this enough to cause edema? it depends on how much of a change in the extracellular fluid volume we have. The vascular space can only hold about 3 liters, therefore if you are trying to push an additional liter into that, the capillary hydrostatic pressure gets so great that fluid will move out into the interstitial fluid OVERVIEW: we an individual consumes large amounts of excess sodium we have sodium retention which we have to buffer to maintain the same, or as close to the same sodium osmolarity. This is at the expense of increased fluid retention. let's say that the pt eventually comes to their senses and decides that they are going to eliminate all high sodium foods because they feel bloated and like crap. When this occurs, it is going to take a couple of days for the kidneys to catch back up. Therefore, at this point, we will begin to lose that excess sodium which will basically be accompanied by the loss of extracellular fluid volume. As we lose this additional fluid, why do we end back at the same extracellular fluid volume that we started at? not as much sodium is coming in, so what is going to happen? well going back to normal means that we need a normal amount of RAAS. the macula densa cells will begin to sense a decreased level of sodium traveling past them, therefore we will get a little bit of renin secretion. ANGII will follow a normal amount along with aldosterone. So that we get these hormones back to a normal level. When doing so our body will try to hold on to a little sodium so that it does not overcorrect from the renal perspective. We will also decrease ADH back to normal so that we can lose the additional extracellular fluid that we retained. This will bring us back down to the starting extracellular fluid volume level. The main point is that we can buffer some pretty extreme sodium changes with hormonal changes and by drinking more water. This is the job of the kidneys to buffer this additional sodium and initiate the changes that need to occur which is how the kidneys link back to the idea of body fluid compartments. These fluid shifts happen because there's a disturbance in the extracellular fluid. SIDE NOTE: The thing that will confuse you on an exam is when you see a question about this phenomenon and it says potassium. We do not have all these extensive controllers for potassium. Generally speaking, if you increase potassium intake your potassium excretion goes up in the kidney. that is pretty much how the kidney handles it. If you have a high potassium intake it is going to be absorbed into the skeletal muscle cells and slowly trickle out into the plasma where it can be filtered out by the kidneys. Furthermore, when potassium is high so is aldosterone. Aldosterone will act on the collecting duct on the principal cells. Principal cells when aldosterone is around are going to secrete potassium through the BK and ROMK channels. They are also going to tell the type A intercalated cells to increase the expression of their hydrogen potassium exchanger. This little group of cells is unable to keep up with the secretion from the principal cells. SO you will end up with net potassium excretion and secretion. Therefore, A high potassium diet causes lots of potassium excretion.
What are the 5 ECG changes that occur with hypokalemia? what are the 6 ECG changes that occur with hyperkalemia?
The normal range of potassium is 3.5 to 5.5 mEq/L which is super narrow in terms of physiological control mechanism. If we go above this range or below this range there can be some pretty dramatic effects. It is very easy to get into trouble potassium-wise. In terms of hypokalemia, the biggest thing that we are worried about is delayed ventricular repolarization. If we look at the ECG there are a couple of things that we might notice, but they might be difficult to see. 1. slightly peaked P wave - P waves will look a little bit like a tent instead of having that nice round top 2. slightly prolonged PR interval - because it takes longer to repolarize 3. ST depression 4. shallow T wave 5. prominent U wave You are more likely to notice the last 3 than the first 2. You will see that something after the QRS complex does not look normal. On the other hand, in states of too much potassium, what we are worried about is basically getting into a situation where we can't control depolarization. This is because it is now being controlled by potassium coming in and depolarizing the cells. We are so concerned about this because it can lead to a situation of v-fib. The things you will see with hyperkalemia before getting into v-fib are: 1. wide, flat P waves 2. prolonged PR interval 3. decreased R wave amplitude 4. widened QRS 5. depressed ST segment 6. tall, peaked T wave You will likely notice the tall, peaked T waves because they can get as high, or higher, as the QRS complex.
What are the 5 ways we can categorize fluid shifts using the diagrams?
The practice problems we are going to do are based on fluid shift diagrams. These diagrams are basically trying to capture the relationship in terms of the ECF volume and osmolarity and the ICF volume and osmolarity. In terms of the volume. the volume shifts are ALWAYS referring to the ECF volume. With a volume contraction, the ECF volume would be moving in and a volume expansion would be the ECF is getting larger than normal. The second way to describe these diagrams has to do with the tonicity. In other words, why the volume shift is happening. We would technically have an isotonic volume expansion. Or we could have a case where we were hypoosmotic or hyperosmotic. So you might have a hyperosmotic volume contraction. This would mean that the ICF was hyperosmotic, and that caused fluid to move from the ECF to the ICF.
What 3 compartments make up the total body water? how do you calculate the total body water? what separates these three fluid compartments? does each compartment have the same fluid volume? what about osmolarity?
Today we are going to cover really basic cell physiology but for our job, it is going to be really important. Most of the time we are giving fluid we are trying to regulate blood pressure. Anytime we are talking about fluid replacement in our job, it is mostly going to be coming from the plasma. But, this plasma is only a small portion of the total body water. The total body water is about 42 liters for a 70 kg male. We will talk about how to calculate this for any individual later in the lecture. The total body water is the sum of the intracellular fluid and extracellular fluid. Therefore, if you add those two values together, that should equal exactly the total body water. In terms of the extracellular fluid, we have an interstitial fluid compartment and our vascular plasma space. Therefore, the sum of your interstitial fluid and your vascular plasma should equal your extracellular fluid. The plasma is separated from the interstitial fluid by the capillary membranes of the body. And then the extracellular fluid is separated from the intracellular fluid by cell membranes. So we have three separate spaces that all have different volumes. In the intracellular fluid, we are looking at 28L, the interstitial fluid is about 11L and the plasma volume is about 3L. BUT all three have the same general osmolarity of 300 mOsm (technically it is 275-295 mOsm). The component particles that make up the 300 mOsm inside the cell are going to be vastly different than what makes up the osmolarity in the extracellular fluid. We will review what these major differences are.
What are the 3 major categories that influence TBW estimates? How do we adjust for each other these factors?
We are now going to go over the factors that influence TBW. 1. Adipocyte 2. gender 3. age The biggest and most common factor that influences TBW is increased adiposity. In terms of adiposity, 10% of adipocyte's mass is fluid. If you have a pt who is a normal healthy 70 kg male, just plug away and use the 60 40 20 rule. BUT if you have a 100 kg male who has 30% body fat (he will provide this information), then we know what 30 kg of our body mass is adipocytes. We have to adjust for this fat mass. We do this by using the 60% rule for our lean tissue mass (70kg), so we would take 70kg times 60%. We would then add the additional transformation for the fat mass by taking 30kg times 10%. This would give us a total of 45L total body water. This is way more accurate than just using the 60-40-20 rule. Gender differences also play a role in influencing TBW. Women generally have about 5% more body fat than men in terms of the difference for total body water calculation. Therefore, for women, we would use 55% to calculate TBW. this means that we can NO LONGER use the 60-40-20 rule. But rather would have to use 67% of TBW to calculate ICF and 33% of TBW to calculate ECF. Age also influences TBW. The elderly are generally more dehydrated which is in part due to loss of muscle mass with age therefore a higher % of the total body weight tends to be adipocytes. Therefore, they sit closer to 50% than 60%. On the other hand, newborns are the exact opposite and are basically little bags of water so we use 70% to calculate their TBW. If you make an adjustment to the TBW based on these factors (obesity, gender, or age), you should use 67% and 33% of TBW to calculate the ICF and ECF respectively. Using 40 & 20% of the weight will overestimate the volumes. My practice problems will demonstrate this more clearly. On the exam, if he wants us to do a simple calculation he will just give us a pt and not say anything. If he wants to make it a little more complicating he will ask us to calculate as accurately as possible and adjust for differences in weight, gender, and age.
What controls fluid movement between the plasma and interstitial fluid? what about fluid movement between the extracellular fluid and intracellular fluid?
We are now going to switch back to talking about the body fluid compartments. Why do fluids move between compartments? Need to maintain homeostasis of each compartment (volume and concentration). 1. Across Cell Membranes: By osmotic forces (from differences in concentration). 2. Across capillaries: By hydrostatic (outward) and colloid osmotic (inward) forces. The big question is - why is fluid going to move from one compartment to the next? If we are talking about fluid moving from the vascular space to the interstitial space we would call it edema. An example would be if the pt has peripheral pitting edema or fluid around their lungs which prevents proper ventilation. These things are only going to occur when the fluid has moved from the plasma to the interstitial space. This movement of fluid is all controlled by Sterling forces. Whether that fluid is moving from the plasma to the IF or from the IF to the plasma, it basically comes down to Starling forces in terms of if we have a hydrostatic pressure pushing out or a hydrostatic pressure pushing in. If we have a lower oncotic pressure in the IF because our proteins are low or high oncotic pressure in the plasma because the proteins are in high concentration. Whatever the case is, the net of those Starling forces will determine where the fluid will travel. On the other hand, fluid that is going to move into the cell (so into the intracellular space) is going to be controlled by osmosis. Osmosis is driven by concentration gradients. If the cells are "saltier" than the extracellular fluid, in other words, if the osmolarity is say 330 in the ICF and 300 in the ECF, fluid is going to move from the extracellular fluid into the intracellular fluid. The opposite can also happen if our extracellular fluid osmolality moves up to 330 and our intracellular fluid is at 300, water is going to move from the ICF to the ECF. The thing that is important for movement into the ICF is the expression of aquaporin channels. Most cells have aquaporin channels because they need to be able to move fluid in order to maintain a proper cell volume. Most of this movement is going to be controlled by potassium.
What are crystalloids composed of? can they cross semipermeable membranes? how are they classified? what are a couple examples of crystalloids?
We are now going to talk about crystalloids. •Contain water and electrolytes •Cross semipermeable membranes •Classified based on concentration of electrolytes in water vs human plasma -Isotonic: Ringer's lactate, 0.9% saline (normal saline) -Hypertonic: 3% saline -Hypotonic: 0.45% saline, 5% dextrose Crystalloid fluids can be isotonic, hypertonic, or hypotonic. Crystalloids are composed of basically water and electrolytes. This fluid can cross semipermeable membranes. Therefore, anytime you give a fluid that can change the tonicity, it will not only affect the ECF but will also affect the ICF. We typically give crystalloids to replenish the ECF volume. But you need to be aware when making a decision on what type of crystalloid we are using that it can affect the fluid movement between the cells and plasma.
What 3 markers are used to estimate/calculate the total body water? what markers are used to calculate the ICF? what about the ECF? what is the 60-40-20 rule? does it apply to everyone? if not, what are the adjustments that are made?
We are now going to talk about the body fluid compartments and how we figured out how much volume they each have. The 60-40 20 rule tells us that about 60% of your total body weight in Kg will correspond to what your total body water is. 40% of our body weight corresponds to the ICF volume. and then 20% corresponds to the ECF. Total body water (TBW) The markers that were used for this originally were antipyrine which is an old-school medication that is rarely used today. It was initially used considering it can basically distribute everywhere. So anywhere water could go into antipyrine could go. Therefore, if you want to know what the total body water is you want to use something that can distribute basically inside the cells, in the plasma, and in the interstitial fluid. Today, we use radio-labeled water. You need to be familiar with the fact that these three items are used to estimate or calculate the total body water. Intracellular fluid (ICF) 40% of our body weight corresponds to the ICF volume. There is no mark for the ICF considering there is no marker we can use that only diffuses into cells and does not remain outside the cells. Therefore, what we do instead is use markers to determine the ECF which will then allow us to calculate the ICF. Extracellular fluid (ECF) The ECF is 20% of our total body weight. The markers for determining the ECF are radio-labeled sodium, inulin, and mannitol. Mannitol is injected into plasma and it can not go into cells and tends to stay in the extracellular fluid space. Inulin which is a prebiotic fiber and also the gold standard for measuring the GFR can also be used as a marker for ECF as it stays out in the extracellular fluid. And lastly, we can also use radio-labeled sodium. Therefore, if you wanted to determine the ICF, you would have to use one of the markers for TBW to determine the TBW. And then you would have to give one of the ECF markers to determine what the ECF volume is. You could then use these two values to determine the ICF volume. Furthermore, if you look at the image you can see different % values under ICF and ECF. This is because the 60-40-20 rule only works under specific circumstances and there are a couple of exceptions to this rule which we will cover in the next NC. One example would be infants as they have a different amount of total body water than we do and it tends to be about 70%. Women tend to have about 55%, not 60%. Elderly people are more dehydrated than young people so they also tend to have lower total body water. So if we have to make an adjustment to the TBW estimate we can not use the 60-40-20 rule. Instead to calculate the ICF you would take 67% of the total body water NOT total body weight. And then if you wanted to know what the ECF volume was you would take 33% of the total body water. How is water distributed across the compartments? You can guestimate volumes with the 60-40-20 rule. You should be able to guestimate volumes using these formulas, and link the specific indicators to each fluid compartment.
What occurs when the ECF is isotonic? hypotonic? hypertonic? what are 3 examples of effective osmoles? what is the calculation to determine plasma osmolarity? what is the normal range for plasma osmolarity?
We are now going to talk about tonicity. We are going to talk about the relationship between the ECF and RBCs which is representing our ICF. Isotonic If we have an equal number of particles on both sides, and therefore, the same osmolarity, the movement of water molecules sort of nets out to be equal. Fluid might move into the cell, but if it does an equal amount will come out so that we are in equilibrium. When this occurs and the osmolarity of the ICF is the same as the ECF, it is said to be isotonic. Hypotonic If the ECF is hypotonic, the cells (ICF) are going to look so salter than the ECF. Therefore, the water molecule will want to move toward the salts in the cell which will make the RBC expand. Therefore, if you accidentally give too much fluid to a pt in surgery, and let's say we were perfusing a little bit of hypotonic saline, but we forgot that bag was dripping and they've accidentally got an extra liter of hypotonic saline - you would basically be exploding the pts red blood cells which can be a problem if we are diluting out their ECF compared to their ICF. If you drew their blood their hematocrit should increase as the cells would be swollen and bigger therefore, the packed RBC mass would be larger. Hypertonic If the ECF becomes hypertonic, fluid will begin to be pulled from the red blood cells causing them to shrink. Generally speaking in comparison to what's outside the cell vs. what's inside the cell, sodium and glucose are effective osmoles. Mannitol is typically used as a diuretic considering it is a sugar that cannot enter cells. Therefore, sometimes physicians will put a pt that is fluid overloaded on mannitol. The Mannitol will be given through IV infusion where it will go into the bloodstream. It is filterable by the kidneys, therefore water will follow the mannitol, causing us to excrete more water. Hence, why it can be used as a diabetic to help get rid of excess fluid. The reason that sodium and glucose are effective osmoles is that we control their uptake. Sodium can not just move into cells. The cell has to be depolarized and the sodium channels have to be open for that to happen. Glucose fits this as well to a moderate extent because within normal physiological ranges of glucose we shouldn't secrete insulin. So as long as the glucose that's out in the plasma is not too high, it will be unable to travel into cells very easily. One way to estimate the plasma osmolarity is to take two times the sodium level (the 2 basically helps account for the chloride) plus glucose divided by 18 plus the bun divided by 2.8. This will give you a pretty good estimation of the plasma osmolarity. What is an effective osmole? If we increase sodium in the ECF it will draw water out of the cell and into the ECF. it is acting as an osmole. It is creating a difference in tonicity that can move fluid from one compartment to another. proteins are also effective osmoles considering they help pull water in one direction and they do not cross cell membranes very easily. Mannitol is also an effective osmole because it cannot be taken up by cells. Therefore, if you want to get rid of it the only way is to filter it through the kidney. Since it is a sugar it will pull water with it. Urea would NOT be an effective osmole anywhere in the body EXCEPT in the collecting duct of the kidney considering in all of the other cells throughout the body we have multiple different types of urea transporters that are generally always expressed. So urea can easily leave the plasma and go into the cells or leave the cells and go out into the plasma as it pleases which means it NOT an effective osmole. We are unable to control its movement. If we are able to control where a substance is likely to build up, it is as effective osmole.
In the intracellular fluid, what is the principle cation that is contributing to the osmolarity? anion? what is largely controlling the tonicity of the ICF?
You do not need to memorize the numbers in the chart. BUT you do need to know what is elevated in the cell versus what things are likely to be elevated outside of the cell. We are going to start by looking at the intracellular fluid side. In terms of our positive charges, the principal thing that is going to be contributing to the osmolarity in this compartment is potassium. We also have lots of magnesium. There is also not a lot of sodium inside the cell, which we should already know. The 14 represents the average amount of sodium that remains in the cell after the net influx of sodium. About 14 mOsm of sodium stays inside of the cell after this. What might be confusing here is that the calcium mOsm inside of the cell is only 0.1 but we know there is lots of calcium inside of the cell considering that is how we get cells to contract. But this 0.1 is referring to the cytoplasmic fluid. If we looked at the calcium concentration inside of the SR it would be a lot higher. But out in the cytoplasm, the free levels of calcium are going to be pretty low. In terms of our negatively-charged products, we have chloride, bicarb, proteins, and phosphate. The phosphate is going to be the most abundant of the anions. The potassium is what is largely in charge of the tonicity in the ICF. And since potassium is controlling the tonicity in the ICF, it will also control the volume in the ICF.
What happens to the resting membrane potiental if the plasma potassium levels are lower than normal? higher than normal? what is the normal range of potassium?
anytime we change the plasma potassium levels it will have an effect on the resting membrane potential of any electrical cell. If our plasma potassium levels are low, then more potassium is going to leave the inside of the cell and go out to the outside of the cell. This is going to make the inside of the cell more negative which lowers the resting membrane potential making it further away from the threshold. This makes it harder to depolarize the cell. If the plasma potassium levels are higher than normal we have the opposite effect. Potassium will enter the electrical cells, moving us closer to our normal threshold. This makes it easier to stimulate/depolarize that cell. Furthermore, the normal range of potassium is 3.5 to 5.5 mEq/L which is super narrow in terms of physiological control mechanism. If we go above this range or below this range there can be some pretty dramatic effects. It is very easy to get into trouble potassium-wise.
