Lecture 15: Osmoregulation PDF

LECTURE 15: Osmoregulation SLIDE 1: Today we are going to discuss the process of osmoregulation, or the maintenance of an organism’s fluid balance by regulating the osmotic pressure of its body fluids. We are going to see the interplay of what we know about osmotic movement of water, the movement o...

LECTURE 15: Osmoregulation SLIDE 1: Today we are going to discuss the process of osmoregulation, or the maintenance of an organism’s fluid balance by regulating the osmotic pressure of its body fluids. We are going to see the interplay of what we know about osmotic movement of water, the movement of fluids through the circulatory system, and now, the system that regulates it. SLIDE 2: The challenge that organisms face is that their cells may face variable osmotic conditions but must maintain a stable composition of extracellular fluid. This balance is necessary and important so that the intracellular fluid remains constant so that the cells are assured to receive the nutrients that it needs for proper functioning. It contributes to normal cellular function by maintaining electrochemical gradients. SLIDE 3: While approaching these ideas, we will focus on three main objectives. First, we must characterize extracellular fluid, what is it, where do we find it, and how can it be regulated? Next, we’ll realize that different organisms use different osmoregulatory strategies, most of which depends on their environments in which they live. Finally, we’ll shift to human osmoregulation and begin our study of that by recognizing and defining fluid intake and thirst. SLIDE 4: We will begin our discussion of fluid regulation by first asking where the fluid in the body resides. The human body is composed of 60% water, and it is found in three places: 1) Some of it is in the cell and is referred to as intracellular fluid. 2) Some of it is between cells and is therefore called interstitial fluid. 3) The last compartment that contains fluid is the circulatory system – the arteries and veins. We see that fluids are not equally dispersed among those three areas. Most of the water is actually within cells, the intracellular fluid compartment. It is the remaining amount, in the interstitial fluid and the blood plasma, that makes up the extracellular fluid. It is this fluid that we will discuss. SLIDE 5: What makes up the extracellular fluid, or ECF? It is a solution of water and solutes, both electrolytes and non-electrolytes. The difference between those solutes is really the charge - non-electrolytes are organic molecules that do not dissociate completely in water; so, they are there in solution, but carrying no electrical charge. While electrolytes will dissociate into ions, resulting, for instance, in salts, acids, bases, some proteins. It is important to remember that all molecules in solution affect osmosis. What are some of the main electrolytes in the ECF? We see sodium and chloride here, while we see phosphorous and potassium in the intracellular fluid in the highest concentrations. If all of these solutes affect osmotic movement, why do we care to differentiate between them? To remind ourselves of the roles and importance that these electrolytes in other functions of the body, underscoring the need to osmoregulate so tightly to ensure they are present in appropriate concentrations in the right locations. SLIDE 6: Let’s remind ourselves of some of those functions. Here we see that one of the three primary functions of the extracellular fluid is to ensure cell function. Those ions are required for cellular function. For example, the maintenance of electrical gradients across the membranes are critical for action potentials to occur, both in the heart and the nervous system. The extracellular fluid is also necessary to preserve cell structure by maintaining appropriate volumes both within the cell and within the interstitial fluid. Finally, the ECF serves as a vehicle for nutrients and chemicals. Remember, the respiratory gases that must be dissolved for exchange to occur. What we notice then is that the volume and solute concentration are both important factors that must be regulated as disturbances to either are detrimental to cellular function. SLIDE 7: Potential problems then arise as organisms are constantly faced with fluctuations in hydration and salinity. Think about your food and water intake on any given day – it all effects your ECF makeup. Here we see an example of the daily water balance of a human. Let’s first look at water loss, we see with urine alone, we lose 1.5 liters per day. Add to that the loss of water that occurs via feces and sweat, and the so-called insensible loss that refers to evaporate loss through skin and lungs, we lose a total of about 2.5 liters per day. With normal functioning, we can’t control that loss, it is a consequence of our physiology. You can imagine a problem arising very quickly if we weren’t able to recapture that loss. What are mechanisms that we have to regain the loss fluids? We can drink, we can get water released from our food (think of fruits such as watermelon, cucumber). We also gain water through metabolism. Remember the water that is produced in the mitochondria as the electrons are passed to oxygen at the end of the electron transport water during chemiosmosis. When these gains and losses are balanced, our concentration and balance of the extracellular fluid is not altered terribly. However, we can also see that the loss and gain of water and ions need not be coupled. In which case, you can gain or lose ions independently of water. Therefore, it can be a challenge to regulate both volume and ion concentration within the ECF. We will then, try to understand how the parameters of osmoregulation can be independently regulated. SLIDE 8: We mentioned that organisms face variation, and that means more than if a human drank the recommended 8-10 glasses of water each day. Imagine the variety of habitats that exist for organisms – freshwater to ocean water to deserts. They all pose differences and challenges in access and availability to water. This is the challenge for organisms, how to maintain an adequate ECF composition. It is a good time to remind us now of the greatest threat to land organisms – desiccation. Osmoregulatory strategies, in some organisms, defend against this threat as we will see. SLIDE 9: How do animals deal with these challenges? There are two distinct ways: 1) conform to the osmotic variation in their environment or 2) regulate. Let’s first see how the conformers manage. If an animal conforms, there is no homeostasis at play, which means it is not investing any regulatory mechanisms in the composition or volume of the ECF. The cells of the conformer will be isosmotic with the environment. Whatever the concentration or osmotic pressure is of the environment, the cells of the animal in the environment will mimic. As you can imagine, this low-energy strategy is quite adaptive for organisms that live in a stable environment with not much variation in salinity or hydration. We tend to see this strategy in marine organisms. The more widespread adaptation is to regulate in order to adjust to changes in the environment. Remember organisms that live in a relatively harsh terrestrial need to protect themselves against desiccation and therefore invest energy (sometimes lots!) to maintain a relatively stable ECF composition. SLIDE 10: Let’s have a look at the potential regulation points of an organism. We see here that the osmotic pressure of the environment is on the x-axis and the osmotic pressure of the extracellular fluid or blood in that case, on the y-axis of both graphs. If we look at the action of a conformer, as soon as there is a little change in the osmotic pressure of the environment, we see a change that is mirrored perfectly in the osmotic pressure of the ECF in the animal. While if we compare the same kind of measurement in a regulator, we see that independent of the osmotic pressure of the environment, the osmotic pressure of the blood of the extracellular fluid will stay constant. What does it mean to stay constant? What parameters need to be regulated by these regulators? Remember, they need to regulate the volume of water, or the volume of ECF. Secondly, they need to regulate the concentration of ions available in the ECF. And third, they need to regulate the osmotic pressure of the ECF. Because remember the influence that osmotic pressure has on cells. It affects the movement of water in that water will always move down it gradient, from an area of low solute concentration to one of high solute concentration. Each of the parameters regulated are all interconnected in that the alteration of each affects the others. SLIDE 11: Let’s have a look at some examples of animals using different strategies. We see the shrimp here as a regulator. We see the range of the environmental osmotic pressures that the animal would encounter while you see that in that range, the shrimp constantly regulates and maintains a constant osmotic pressure in each environment. Next, we can look at the mussel, a conformer that does not regulate anything in relation to its osmotic pressure - its blood osmotic pressure will mimic perfectly the ambient osmotic pressure with a one-to-one correspondence. There are organisms that a bit more complicated because depending on the range of osmotic pressure they're in, they will either conform perfectly or regulate a bit and that is what we see here in the green crab. A kind of intermediate strategy where they regulate in some ranges. You see that on those low pressures, they regulate and then they become conformers. When you consider the range of habitat, you see that some water environments can be nearly without any salt, while some will have a very high osmotic pressure. So that requires really some adaptation in osmoregulation. SLIDE 12: Fish are interesting to consider in osmoregulatory stories as they are unique in that their circulatory system is in direct contact with their aquatic environments due to their gills as respiratory organs. In addition, there are two very different aquatic environments in which fish reside – marine and fresh waters. We will now have a close look at the osmoregulatory strategies of bony fish inhabiting fresh water. First, we see the freshwater fish, a bass, here. The aquatic environment around it has an osmotic pressure of approximately 3 milliosmoles, practically pure water, no solutes. That is in contrast to the approximately 300 milliosmoles within the body that is typical. The tissues of freshwater fish then, are hyperosmotic, to the environment, meaning they contain more solute than their surroundings. Water will therefore want to enter the cells of the freshwater fish, so we call the environment dilute. In addition to diluting the salt concentration within the cells, the cells are in danger of lysing if too much water enters. How do freshwater fish manage? By a number of adaptations seen here. First, they actively pump what little salt the freshwater contains into their gills to counteract any salt that they may lose to diffusion down their concentration gradients. In addition, they excrete a large amount of dilute urine to remove any water that entered via osmosis. Here we see the investment of energy to prevent the loss of salt and the gaining of water. SLIDE 13: Marine fish, like the cod seen here, face the opposite osmoregulatory challenge, they live in sea water which is much more concentrated than the cells, which remain at 300 milliosmoles while seawater is approximately 3 times that. The tissues of marine fish then are hypoosmotic to its environment and water has the tendency to want to leave the cells via osmosis while salt could diffuse into the cells. We therefore call this environment a desiccating environment. How does the marine fish deal with its osmoregulatory challenges? The approach again is two-fold. First it actively pumps salt out of its gills to remove any salt that has entered via diffusion. In addition, they will excrete a highly concentrated urine to minimize water loss. While the strategies of marine and freshwater fish differ, they are united in that they invest energy to pump salt (sodium and chloride ions) actively. This investment in energy to osmoregulate underscores its importance to the life of the organism. SLIDE 14: I’d like to take a minute to describe an adaptation that is seen another marine fish – the cartilaginous fishes such as the shark. While they live in the same marine waters as the bony fish and face the same concentrated environment, their internal osmotic pressure differs and therefore so do their osmoregulatory strategies. This difference is due to the increased amount of urea (a nitrogenous waste product) in shark tissue. Because urea can be toxic in high amounts, the shark also produced a substance called trimethyl amine oxide, or TMAO, as a protect against tissue damage brought on by urea. Because total solute concentration determines osmolarity, and not specific solutes, we see the tissue of the shark with a solute concentration greater than 1000 milliosmole concentration of the surrounding water, making the shark tissue slightly hyperosmotic to the environment, like the freshwater fish. Therefore, its osmoregulatory strategies are to limit drinking (there is some fluid intake while feeding) and actively move salt out of the tissues via the gills and a specialized gland dedicated to their removal, called the rectal gland named more for its location in the body rather than its function. SLIDE 15: I think we have made quite the case for the importance of fluid balance in organisms. Let’s focus now on our third and final topic for the day – thirst and fluid intake. We can agree on how important water is for life. It has been shown that while we can withstand days of no food, we cannot withstand the lack of water for long. SLIDE 16: Let’s talk about why that is. We use the term dehydration to encompass the idea that we lose more body fluids than we take in. And as we just learned, that disrupts the balance of water and minerals in the body. How? We can see different sources of dehydration, exercise or disease, or others that we will discuss moving forward. We also see that there are gradations of dehydration. For example, at about a 4% loss of water, symptoms may appear as fatigue or dizziness. Whereas with a 10% reduction of water, we start to see more extreme and potentially longer- lasting symptoms of impaired renal function, seizures, or heart failure. To fully understand the implications of dehydration, we must first differentiate between two types of dehydration. Though we may not perceive these differences, the underlying mechanisms differ. The first is isotonic dehydration. This means you're dehydrated, but your ECF is isotonic. You maintain the same osmotic pressure as in normal conditions. It’s also called "hypovolemia", referring to the low volume that results. That means you have less volume of the ECF generally, it leads to a decrease in volume of blood plasma. And consequently, you have less ECF in circulation. So isotonic dehydration is when you don't have enough ECF, you've lost fluid without really changing concentration. You’re dehydrated, you don't have enough fluid, but the concentration of solutes is okay. This can result from a major injury that results in blood loss, or from diarrhea. The second type of dehydration is called hypertonic dehydration. In this case, you have high electrolyte levels, generally salt, so it is also referred to as hypernatremic dehydration, or too much salt. This is true dehydration because it means that you don't have enough water, but salt is present. This can be in response to excessive sweating, too much salt intake. Though these two dehydrations have different causes and are independent of each other, both are dangerous. Due to the different causes, they are regulated and restored differently. SLIDE 17: Because dehydration can be so detrimental to the functioning of a human, you can imagine that salt and water in the extracellular fluid is controlled. There are two approaches - you can regulate your intake of water and salt or you can regulate the output, through the process of excretion, that we will discuss next time. Essentially you can regulate how much goes in and how much goes out. The net difference between those two actions determines whether you gain or lose fluids, water, or salt. We will focus on the regulation of intake here. SLIDE 18: Thirst is what primarily controls our intake, as it is a brain response to dehydration. We can target the brain region that is implicated in this response by looking at PET scans of thirsty patients. We see it is areas of the hypothalamus, the regulator of physiology, that are activated. When the individual drinks, the activity ceases. This tells us that this is an active response. How and where does the brain signal that you are dehydrated? The hypothalamic thirst center is activated by dehydration, and it stimulates a behavioral response to drink. Upon drinking, thirst is satiated and sensed by the stretch of the stomach among other stimuli and thirst will stop. SLIDE 19: Let’s look at this in a bit more detail. Let’s first look at the response to what we call ‘true dehydration’, or hypertonic dehydration, the hypernatremic condition in which the concentration of electrolyte levels is too high. The stimulus to this then is an increase in osmolarity detected by osmoreceptors in the hypothalamus. If we compare that to hypovolemia, or isotonic dehydration, you should see that there is no change in osmolarity, so this would not trigger the osmoreceptors into action. Therefore, there is a different class of receptors, the baroreceptors, the sense the change in pressure brought on by the change in blood volume. Each of these pathways then respond differently to their different stimuli. Let’s discuss the response to true dehydration when the ECF is too concentrated. The danger then is that the cells will lose water due to osmosis as it diffuses out of cells to the ECF, therefore this can be referred to as intracellular thirst. A response then is to replace fluid via drinking so that the ECF will dilute and restore to homeostatic levels. If, however, hypovolemia is the culprit behind the dehydration, then the cells are not in danger of losing water as the ECF has the proper concentration. However, blood pressure and ECF volume are decreased, so we refer to this as extracellular thirst. Simply drinking water does not treat hypovolemic, extracellular thirst as it would only dilute the ECF. Instead, salt must be ingested along with water to increase volume while keeping the solute concentration stable. SLIDE 20: Here we see a summary of what we discussed in comparing the regulation of the two types of thirst. We see a difference in what is being monitored: electrolyte concentration or fluid volume, a difference in stimulus: is there an increase in osmolarity, or a decrease in plasma volume?, the actual receptors: are they sensing osmolarity or pressure and what part of the system is being affected: inside or outside of the cells. SLIDE 21: Of course, that affect the response or treatment. Dehydration can be treated with the ingestion of water while hypovolemia requires ingestion of both water and salt. SLIDE 22: Let’s tease apart those two different pathways a bit more. First with intracellular dehydration that results from an increase in plasma osmolarity. We know the risk here is that water will have a tendency to leave cells via osmosis and the cells will shrink, affecting their function. We see that increase in extracellular fluid osmolarity detected by osmoreceptors that are in the hypothalamus. In addition, you will have also some peripheral problems like a reduction in saliva production. This activates hypothalamic thirst center, which will then activate response, which is you being thirsty. When the osmolarity of the ECF is restored, the osmoreceptors stop sending their signal, thirst is quenched and it's back to normal. SLIDE 23: We see a different case in extracellular, or hypovolemic, thirst. Remember that this results from a decrease in blood plasma volume, a component of the ECF. We see that decrease directly decreases blood pressure. We know the circulatory response to that is to vasoconstrict to increase the pressure via increased resistance, and also increase heartrate. Both can be risky over time. The osmoregulatory response senses this drop in blood pressure due to baroreceptors at the kidney whose perfusion decreases. Baroreceptors stimulate the hypothalamic thirst center directly as we just saw for intracellular dehydration. But we also said that hypovolemic thirst needs to be treated with salt as well. How is this accomplished? It is through a hormone cascade that is initiated by that reduced perfusion and response through the kidney that is mediated by this angiotensin II seen here that both stimulates the thirst center and is involved in the pathway that signals the body to retain sodium, thereby increasing the concentration. SLIDE 24: Finally, I’d like to focus on salt for a moment. We have seen its importance in the context of balancing fluids. It is, however, important in its own function. We are already aware of its role in action potential initiation and conduction, membrane potential maintenance, it is a critical nutrient for animals. Animals acquire salt in food. This does not pose a problem for carnivores, or omnivore, as their food is rich in salt - sodium and chloride. However, herbivores have a problem to contend with in that their food source – plants – do not have much sodium. Because sodium is not a required nutrient for plants, they do not acquire it from the soil. They are deficient in it with no effect. As this deficiency is passed to the herbivores that eat them, it poses a problem. They are often in a sodium deficit, have an intense salt hunger, and actively seek it out, often from exposed salty mineral deposits in nature, and artificially placed salt licks used by farmers.