In order for the cells in the body to operate properly, they need liquid surrounding them and filling them. The amount and composition of this liquid is critical to cells' proper functioning; and that's the subject of this chapter.

There are three issues which are closely related to this topic; they are water balance, electrolyte balance, and acid-base balance. Maintaining all of these balances involves the urinary system, the respiratory system, the digestive system, the integumentary system, the endocrine system, the nervous system, the cardiovascular system, and the lymphatic system--pretty much an all-body effort.

At birth, we are really waterlogged, probably as a result of floating around in a membrane filled with fluid for months before birth. Babies lose much of this fluid in the first few days of life, but their bodies still contain a great deal of fluid. Once you're an adult, your water content has pretty much stabilized at 55-60%--a bit less if you're female. The biggest determining factor in the precise percentage of your body weight which is water is the amount of adipose tissue you have. Fat has almost no water in it, so the more fat tissue you have, the lower your percentage of water. That's why women have a lower percentage of water than men--generally women have more subcutaneous fat than men--even women in excellent shape. The elderly have a little less body water than younger adults, more like 45% or so.

Your total body water (TBW) is distributed between two kinds of locations. Some of it--about two-thirds--is found inside cells--remember that cytoplasm is mostly water. This is called intracellular fluid (intra- means inside) or ICF. The rest is found outside cells; this is called extracellular fluid (extra- means outside) or ECF. These two kinds of locations, ICF and ECF, are called fluid compartments, because they're separate and have different effects on the body as a whole.

The extracellular compartment can be further divided into sub-compartments. These include the fluid which occurs between cells and bathes them at all times. This fluid is called interstitial or tissue fluid. Another sub-compartment holds the fluid found inside vessels of the circulatory and lymphatic systems--plasma and lymph--intravascular fluid. And the sub-compartment includes what are generally called transcellular fluids, for example, cerebrospinal fluid; peritoneal, pleural, and pericardial fluid; the fluids inside the eyeball; fluids in the digestive tract; and urine.

Now fluid doesn't just go to its own corner and stay there; it is continually exchanged among the compartments. Wherever there is an osmotic gradient, fluid moves with the gradient; water diffuses easily through all the membranes in the body. These gradients are determined more by the relative concentrations of electrolytes than by any other solute simply because of the relative abundance of electrolytes in fluids of the body. There is also a role played by the hydrostatic pressure of blood inside vessels; because the pressure inside arteries is always higher than outside, there is a tendency for fluid inside the vessels to continually leak out into the interstitial fluid. Some of that fluid is then picked up by lymphatic vessels for return to the circulation later.

So fluid that enters the body is mostly taken in by eating and drinking. This fluid, once it gets to the intestine tends to diffuse by osmosis into the bloodstream. From the bloodstream it enters interstitial spaces, mostly because of capillary filtration, which is due to the hydrostatic pressure of blood inside the vessels. Once fluid surrounds the cells, it moves fairly freely into and back out of the cells. Cells undergo frequent exchanges with their surrounding interstitial fluid. Then some of this interstitial fluid enters the lymphatic vessels, which carry it to the upper part of the torso where they empty back into the circulation.

In order to maintain appropriate water balance, the daily intake of water should roughly equal the daily losses of water. The main inputs into the system are water found in food you eat and in liquids you drink. Of course, most foods contain less water than most beverages, so things you drink act as a better water source than things you eat. There is also a small amount of water produced as a by-product of metabolism. Remember that when you build most organic molecules in your cells, you bond things together using dehydration synthesis? Well, this means you remove a water for each chemical bond you form between two smaller molecules. This removed water is available for cells to use--about 200 ml a day. Considering you get about 1600 ml per day from fluids and another 700 ml per day from foods, the 200 is a fairly important input--close to 10%.

You lose water in a number of ways. Most of your water loss is in urine--about 1500 ml per day. If you have a shortage of water in the body, urine output is decreased a great deal, but it can never be reduced to zero. That's because the kidneys need to eliminate a certain amount of waste chemicals each day, and these chemicals must be dissolved in water in order to be eliminated. About the bare minimum of urine that can be produced, no matter how serious the water shortage in the body, is 400 ml per day.

Other sources of water loss include feces (excreted solid waste)--about 200 ml per day; breath--about 300 ml per day--more if it's cold or you work hard, less in humid weather; and sweat--about 100 ml per day plus more if you're exposed to hot weather or work very hard.

If your body is short of fluid, you can reduce some of these outputs, like urine, but not all of them. The water in expired air, feces, and sweat is pretty much unavoidable, as is the minimum amount of urine.

If you can't prevent some minimum level of loss, then it is very important to control intake. The only way to make up for unavoidable losses is to take in more water in the first place. The main regulator of how much water you take in every day is thirst. This sounds simple enough, but the fact is that the regulation of thirst is a fairly complicated matter.

So what makes you thirsty? Two things as a rule, both related to a deficiency of water in the body. This deficiency means that blood is more concentrated than usual--the amount of dissolved solids is high compared to the amount of water. Osmoreceptors in the hypothalamus of your brain monitor the concentration of blood. These receptors detect changes in the osmolarity--concentration--of the blood. When the blood's osmolarity goes up (meaning you're short of water), then the hypothalamus nudges the posterior pituitary, which is right next door in the brain, to produce a hormone called anti-diuretic hormone (ADH). If you keep track of ADH's name, it's easy to remember what it does. Anti- means against or contrary to; diuresis is a high level of urine production. So its name says anti-diuretic hormone should reduce the amount of urine your kidneys produce; and so it does. We'll talk more about that later; what else ADH does is stimulate the thirst center in your brain.

This thirst center has a couple of interesting effects. One is that it causes saliva production to slow down. This makes your mouth feel dry and pasty--one of the main indicators of thirst. Makes you want to take a drink pretty badly. It also directly causes feelings of thirst from the brain. This sense of thirst causes you to drink water, which cools and moistens your mouth, giving immediate relief. The other temporary shut-down of the sense of thirst is from the stretch receptors in the stomach. If you drink enough water to fill the stomach, it feels full and uncomfortable, which causes you to quit drinking water. Good thing too, because long-term shut-down of the thirst center takes up to 45 minutes. If you had to keep drinking until the thirst center shuts down, you'd be drinking steadily for 45 minutes--you'd blow up! These two short-term mechanisms keep us from drinking too much water in the short-run while your system processes the fact that now you have plenty of water.

Now you might remember that I mentioned two things cause you to get thirsty. The first one is the detection of high blood osmolarity by osmoreceptors. The other one is detection of lowered blood pressure, also monitored in the hypothalamus. When you have less fluid available in the body, your blood will contain less water than normal, so total blood volume is decreased. This lowers blood pressure because there isn't enough blood to fill all the blood vessels. This lower blood pressure causes secretion of another hormone called angiotension II, which also stimulates the thirst center. So your thirst center gets double-whammied when you get dehydrated--once by ADH and again by angiotensin II. Effects are the same here as we saw with the osmoreceptors.

It doesn't take much decrease in blood volume to set off intense thirst--a 10% blood loss is plenty. And it takes even less increase in osmolarity to set up thirst--a 2 or 3% gain is enough. The only solution for dehydration is to take in more water. Thirst is the mechanism which prompts us to do so. Once the water you drink makes its way to the bloodstream, the osmolarity of your blood goes down and your blood pressure rises slightly; this reverses the whole process that made you thirsty in the first place. Homeostasis again, isn't it?

Now there's a limit to what we can do in the way of regulating water output. We've already talked about the fact that some water losses are unavoidable--sweat, water in expired breath, water in feces. About the only way to significantly control water output is to reduce urine volume; and there is a minimum urine output required to excrete wastes. Of course, none of this replaces lost fluids; the best we can do on the output side of things is to support existing fluid levels and slow down the loss.

Since we haven't really talked much yet about how the kidneys work (that's for next semester), let's get a few things straight. In the kidney tubules--the business end of the kidneys--substances, including water, are filtered into the tubule. That means they are destined to be excreted as urine, unless they are reabsorbed further down the tubule. Reabsorption returns fluid (and other things) to the ECF. Things that are filtered, but not reabsorbed get excreted in urine.

It's also helpful to remember that generally water follows sodium in urine production; when sodium is filtered, water goes along with it, and when sodium is reabsorbed, water is reabsorbed with it too. The only way to interfere with this sodium-water coupling is the hormone, ADH, which controls water output independently of sodium losses.

Here's when that matters: When you're dehydrated, you have a deficiency of water, but your blood concentration is increased. So there’s too much dissolved solute—including sodium—in your blood. Your blood volume is down, but its sodium concentration is up. What you need to do at this point is get rid of some sodium, but not lose the water that generally goes with it.

Remember from our earlier discussion of thirst that dehydration raises the osmolarity of blood. This is detected by the osmoreceptors in the hypothalamus, which stimulates the posterior pituitary gland to secrete ADH. This should be familiar to you; we just talked about it. Remember that ADH stimulates the thirst center, but we also mentioned it decreases urine output. Here's how: In the filtration process all that excess sodium in the blood is filtered into the kidney tubule, and water follows it--we talked about the fact the water follows sodium, didn't we? Now ADH goes to work on the kidney tubule to increase reabsorption of water. Reabsorption means the fluid is returned to ECF, so it won't be excreted as urine. But ADH blocks the reabsorption of socium, so the sodium isn't reabsorbed along with the water. The upshot is that you retain the water in your body, but not the sodium.

This means the volume of urine made is reduced because it contains so much less water, but the amount of sodium in the urine is higher. This is just what we needed to happen, isn't it? We eliminate less water, but get rid of a lot of sodium. That slows the decline in blood volume, keeping blood pressure up as much as possible, and slows the rise in osmolarity of the blood. This helps to stabilize the body's water content as much as possible until more water can be taken in--the only real solution to dehydration.

Now if the body is overhydrated--too much water, we'd have just the opposite problem. Blood pressure would be too high because there's too much blood in the vessels, and the osmolarity of the blood would be too low because all that water would dilute it. This situation inhibits ADH release, so the renal tubules would reabsorb less water, increasing urine output and reducing the total body water. There would be more sodium left in the blood and less found in the urine.

All of this input/output regulation is complicated. Get these basics worked out for now, and it will be much easier for you next semester when we talk about it again during our discussion of the urinary system.

Since water balance involves the amount, composition, and distribution of water, disorders of water balance can be caused by problems with any of these three factors. You can have too much or too little water; you can have too concentrated or too dilute body fluids; and you can have fluid poorly distributed among the various fluid compartments.

Volume Depletion. This is also called hypovolemia, and it occurs when total body water is decreased, but the osmolarity of the remaining fluid is normal. It results from loss of water and sodium without replacement. This can happen after hemorrhaging, burns, chronic vomiting or diarrhea, and in Addison disease, a disorder of the adrenal gland (aldosterone hyposecretion--more on aldosterone later) causing poor reabsorption of water and sodium in the kidney tubules.

This is one reason the body monitors both blood pressure and blood osmolarity in order to determine what to do about fluid levels. If only blood osmolarity were monitored, the hypothalamus would think this situation was normal, and you wouldn't be stimulated to reduce urine output or to drink more. Yet you'd be in serious trouble. Because lowered blood volume lowers blood pressure, monitoring blood pressure gives your hypothalamus a chance to figure out that something is wrong here and move to correct it.

True Dehydration. This is also called negative water balance and occurs when you eliminate more water than sodium, causing an increase in the osmolarity of the ECF. It results from a lack of available drinking water, for example when you're out working and don't have water available to replace your losses from sweating. It can also happen to very sick or elderly people who can't get water for themselves and are unable to ask for it; if caretakers aren't careful and attentive to providing plenty of water and assistance to drink it, then these people are in as bad shape as someone lost in the desert. Other conditions that cause negative water balance include diabetes mellitus (abnormality of glucose metabolism which leads to increased urine production), diabetes insipidus (hyposecretion of ADH), overuse of diuretic medications (some blood pressure medications), and prolonged exposure to cold.

The effects of either kind of water deficiency--hypovolemia or dehydration--are similar. Left untreated, the affected individual can go into circulatory shock, where the blood volume is too low to support normal circulation of blood to all the tissues that need it, and neurologic malfunctions because the brain cells have become dehydrated. An individual begins to show signs of trouble when even as little as 5% of total body water is lost; 10% losses lead to serious problems, and 20% losses are generally fatal.

Volume Excess. Fluid excess of any kind is much less common than fluid deficiency because the kidneys are very good at eliminating excess fluids. Volume excess occurs when there is simply too much fluid in the body. Total body water is increased, but the osmolarity of the fluid is normal. This happens when sodium and water are both retained by the kidneys; the ECF will have the proper concentration. The most common causes of volume excess are aldosterone hypersecretion (Really, we're going to talk about aldosterone soon!) and renal failure.

Hypotonic Hydration. This is also called water intoxication or positive water balance and occurs when more water than sodium is retained or ingested. The ECF becomes hypotonic, which causes cells to take up water and swell. It happens when large amounts of water and salt are lost in sweat or urine and replaced with pure water containing no electrolytes; it also happens in conditions of ADH hypersecretion.

The effects of overhydration of either kind include pulmonary and cerebral edema--that is accumulation of fluid in lung and brain tissue, which causes tissue swelling.

Compensation. Because it takes the body a while to get up to speed on overhydration and dehydration, we do have some useful temporary mechanisms that will compensate in the short term until the body gets itself back into homeostatic equilibrium. When you are overhydrated, your heart rate drops. To deal with the increased blood volume without damaging tissues, your blood vessels dilate, your capillary beds dilate, and sinusoids (enlarged spaces in organs) expand. This takes the pressure off the rest of the circulatory system. Of course, the only long-term solution to the problem of overhydration is to produce more urine until the excess has been excreted.

When you are dehydrated, your heart rate increases in an attempt to deliver more blood to tissues that need it. To help increase blood pressure when blood volume is down, your blood vessels constrict, capillary beds close, and sinusoids constrict and empty. You also produce ADH to reduce urine production until the problem is fixed. The long-term solution is to take in more fluid until homeostasis is restored.

Fluid Sequestration. Sequester means to isolate or separate; here it is a reference to fluid being kept separate from the rest of the body fluid. This is a condition in which excess fluid accumulates in a given body location. Total body water is normal, but there is a drop in the volume of circulating blood because water is diverted to other compartments. The most typical example of fluid sequestration is edema, the abnormal accumulation of fluid in interstitial spaces. This leads to swelling of the affected tissue. Another example is hemorrhaging, which may cause blood to pool and clot in tissue instead of continuing to circulate in the vessels where it belongs. Yet another is pleural effusion, the accumulation of fluid in the pleural space, the space between the two-layer membrane surrounding the lungs. Several liters can accumulate here.

As you may remember from lesson 1, electrolytes are substances that ionize in water to form a solution capable of conducting electricity. Electrolytes are very important in the body because they are chemically reactive, because they determine the electrical potential across cell membranes, and because they affect the osmolarity of body fluids. The ions formed by electrolytes that are most important in the body are sodium (Na⁺), potassium (K⁺), calcium (Ca⁺²), hydrogen (H⁺), chloride (Cl^-), bicarbonate (HCO₃^-), and phosphate (PO₄^-3). We'll talk about hydrogen and bicarbonate ions later, because they're mostly important to acid-base balance, but the others we'll talk about here.

Sodium has many important physiologic functions. It is the principle ion responsible for the membrane resting potential of cells; inflow of sodium is essential to the depolarization necessary to make nerve and muscle cells operate properly and sodium is important to the transport of many substances across the cell membrane. It is also the principal ion found in ECF; it's the ion most responsible for the osmolarity of body fluids, total body water, and water distribution among the fluid compartments. The sodium-potassium pump is an significant source of body heat; and sodium bicarbonate is an important buffer of ECF.

Sodium Homeostasis. Dietary deficiencies of sodium are rare. The average diet includes many times the sodium needed, so the body's principal problem when it comes to sodium is excreting the excess.

Aldosterone. There are several mechanisms that control sodium excretion; the primary one is aldosterone, which is produced by the cortex of the adrenal glands.

Several conditions can stimulate the production of aldosterone: low blood pressure (water deficiency), hyponatremia (low sodium concentration in blood), and hyperkalemia (high potassium concentration in blood). Aldosterone stimulates the kidney tubules to make sodium-potassium pumps which pump sodium back into the ECF and potassium into the filtrate. So there will be less sodium (and water--remember, these travel together) and more potassium in the urine. This effect happens fairly quickly, so changes in sodium levels can occur soon after the imbalance occurs.

Because of this action, aldosterone is called the salt-retaining hormone; urine can be virtually sodium-free if the aldosterone level is high enough. Aldosterone can help support the existing blood volume and sodium concentration until oral intake of fluid and sodium increases. High blood pressure inhibits the production of aldosterone so that the kidneys excrete huge amounts of sodium; the idea here would be that because water goes with the sodium, the total body water and blood volume should decrease, lowering blood pressure.

ADH. ADH also plays a role in controlling sodium levels because, as you remember from just a little bit ago, it modifies water excretion independent of sodium excretion, which changes the sodium concentration of ECF. This means ADH doesn't do anything about the overall amount of sodium in the body, it just retains water to help dilute the sodium present. So ADH slows the increase of sodium concentration in body fluids. A drop in sodium concentration inhibits ADH release, so that more water is excreted, raising the sodium concentration in the blood.

Atrial Natriuretic Factor. This hormone is produced in the atria of the heart in response to the stretching of the heart muscle seen when blood pressure rises. Its name tells us a great deal about how it works. Atrial is a reference to the source of the hormone, the atria of the heart. Natri- means sodium; -uretic means urine. Natriuretic means something that puts sodium into urine. And that's what atrial natriuretic factor does; it inhibits sodium (and water) reabsorption in the kidney tubules so that the kidneys eliminate more sodium and water, lowering blood pressure.

Other Factors. Many other substances have some effect on sodium homeostasis. Estrogens, female sex hormones, mimic the effects of aldosterone, which explains the fluid retention experienced by many women during pregnancy and at certain points in the menstrual cycle. Progesterone, another female sex hormone, decreases sodium reabsorption, which causes increased losses of sodium and water by the kidneys. And glucocorticoids produced by the adrenal cortex promote sodium reabsorption in the kidney tubules. Additionally, regulation of salt intake can influence sodium homeostasis; people who are depleted of sodium often experience salt cravings.

Sodium Imbalance. Sodium concentration of body fluids generally remains fairly constant because you tend to lose or retain water along with sodium, which keeps the concentration of sodium in fluids pretty much the same. Hypernatremia can occur in people who receive intravenous saline solution, resulting in water retention, hypertension (high blood pressure), and edema. Hyponatremia can occur when urinary and sweat losses of water and sodium are replaced with water only. This, of course, is the same thing as hypotonic hydration or water intoxication. The solution is to eliminate the excess water.

Potassium is the most abundant ion in ICF and is therefore the biggest influence on ICF osmolarity and cell volume. Potassium, along with sodium, is responsible for the resting membrane potentials and depolarization needed for nerve and muscle cell operation and is equally as important as sodium in the sodium-potassium pump.

Potassium Homeostasis. Potassium is closely linked to sodium; generally the more potassium in urine, the less sodium, and vice versa. That's because the main influence on sodium excretion is aldosterone, which causes sodium reabsorption and potassium excretion at the same time.

Potassium Imbalances. Of all the electrolytes, potassium is the most dangerous when out of balance. This can cause death fairly quickly if not corrected.

Hyperkalemia. What happens with hyperkalemia depends on whether the potassium level in blood goes up quickly or slowly. A quick rise might be caused by anything that damages cells because most of the body's potassium is found inside the cells; damaged cells leak their potassium into interstitial fluid where it will easily be exchanged with the blood. So crush injuries, hemolytic anemias (where many red blood cells lyse in a short period of time), or transfusion of old blood (since RBCs leak potassium as they age) will cause a rapid and significant increase in ECF potassium levels. To understand what this means, we have to understand that normally potassium continually diffuses out of cells, while the sodium-potassium pump pumps it back in. With all this potassium hanging around outside the cell, the concentration gradient is reduced, so potassium stops diffusing out. But it's still being pumped into the cell. So now we have a cell with more potassium than usual inside, and this brings it close to the same condition that sets off muscle and nerve cells. They become abnormally excitable; the most serious result is sudden cardiac arrest.

Strangely enough, just the opposite thing happens when the rise in ECF potassium level is slow. This can happen in aldosterone hyposecretion (remember that aldosterone causes potassium excretion), renal failure, and acidosis (something we're going to talk about later). One of the things that happens when a nerve or muscle cell is triggered is that sodium rapidly enters the cell. Well, a slow rise in potassium level inactivates the little gates that let sodium in, so the cell can't be triggered--no sodium rush to set things off. So nerve and muscle cells become abnormally un-excitable.

Hypokalemia. This isn't so common because dietary deficiencies of potassium are pretty unusual; most diets have plenty of potassium, even if they aren't so hot in other ways. Sometimes, though, in people whose appetites are depressed, a deficiency develops simply because the person doesn't eat enough food at all. Hypokalemia can also develop as a result of heavy sweating, chronic vomiting and diarrhea, excessive laxative use, aldosterone hypersecretion (when you'd excrete too much potassium), and alkalosis (more on this later too). Now with ECF potassium levels way too low, we have the opposite problem we saw with a rapid rise in potassium level. With not enough potassium hanging around outside the cell, too much diffuses out. This makes the resting membrane potential so great that it would take a huge stimulus to trigger a muscle or nerve cell to fire. So the cells are less excitable than they should be--same problem as with slow potassium rises, but for a very different reason. The result of this is muscle weakness, loss of muscle tone, depressed reflexes, and irregular electrical activity in the heart muscle.

Chloride is the most abundant anion in ECF, so it is a major determinant of its osmolarity. Chloride is also important in forming stomach acid, in red blood cell uptake and release of carbon dioxide, and in regulating pH.

Chloride Homeostasis. Chloride is so strongly attracted to sodium, potassium and calcium (all cations) that its homeostasis is simply an effect of sodium homeostasis. They travel together, so what increases sodium levels also increases chloride levels, and vice versa.

Chloride Imbalances. Hyperchloremia is usually due to excess intake, either in the diet or when IV saline is administered. Hypochloremia is generally a side effect of hyponatremia. Chloride imbalance mostly affects the pH of body fluids.

We've already talked about the importance of calcium in bones and about some other important physiologic functions of calcium, including its importance in muscle contraction, its function as a second messenger for hormones and neurotransmitters, and its role in blood clotting. Cells tend to keep calcium out because they contain so much phosphate; the last thing cells need is to build up threshold levels of calcium and phosphate so they begin to crystallize, making bone. (Check the last lesson for the information on ectopic ossification.) So they pump lots of calcium out and sequester what's left in the endoplasmic reticulum, leaving no way for the calcium and phosphate to get together inside the cell.

Calcium Homeostasis. We've already talked about this too; remember PTH, calcitriol, and calcitonin?

Calcium Imbalances. Hypercalcemia can occur during alkalosis, hyperparathyroidism, and hypothroidism. Excess calcium reduces cells' permeability to sodium which inhibits the firing of nerve and muscle cells. Hypocalcemia can occur in vitamin D deficiency (we talked about this before), pregnancy, lactation, acidosis (really, it's coming soon), hypoparathyroidism, and hyperthyroidism. The lack of calcium increases cells' permeability to sodium, which makes nerve and muscle cells overexcitable. Uncontrolled muscle contraction, which can obstruct the airway, results.

Phosphates are found mostly in ICF, where they're produced as a result of breaking down ATP. They're important components of many essential compounds in the cell, including nucleic acids, phospholipids (in cell membranes), and energy-related compounds like ATP and GTP. They also activate many metabolic pathways by reacting with participants in the reactions, and they act as buffers.

Phosphate Homeostasis. There's usually sufficient phosphate available in the body to meet its needs. Some is lost to filtration in the kidney tubules, but it's easily reabsorbed if needed. Remember that PTH increases phosphate excretion to push calcium concentrations up in ECF. The pH of urine influences phosphate excretion too. But the levels remain pretty constant in spite of all these influences; the body's pretty good at maintaining phosphate levels.

Phosphate Imbalance. This is not a big deal either as a rule. The body can tolerate wide variations in phosphate levels, so imbalances are not usually a problem.

If you remember the things you learned from this chapter for lesson 1 (pages 927 and 928), then you can skip these pages in the reading this time. We'll carry on from there to talk about physiologic buffer systems and the effects of pH imbalances.

The respiratory system has a fairly strong buffering capacity, especially compared to the chemical buffering systems you've already learned about. It works so well because adding carbon dioxide to the system raises the hydrogen ion concentration (which lowers pH), and removing carbon dioxide from the system lowers the hydrogen ion concentration (which raises pH). If this doesn't make sense to you, look back on pages 927 and 928 to the stuff on the bicarbonate buffer system.

Carbon dioxide is produced by metabolic processes and eliminated by the lungs; when carbon dioxide concentration in blood rises, chemoreceptors detect it, and the ventilation rate increases. Because this expels carbon dioxide, it reduces the carbon dioxide levels. When carbon dioxide level falls, the ventilation rate is decreased. Because ventilation has such a rapid effect on carbon dioxide levels, this is a quick way to get an effect on pH, but it doesn't have the buffering capacity of the next system we're going to talk about.

The kidneys can neutralize much more acid or base than the respiratory system; that's because the kidney tubules secrete hydrogen ions directly into the tubular fluid. These are the only organs that actually expel hydrogen ions from the body. Now we wouldn't want the pH of urine to fall too low; if it does, the concentration gradient for hydrogen ions would reach the point that no more hydrogen ions could be secreted. What happens to prevent this is that these ions in tubular fluid are bound to bicarbonate, ammonia, and phosphate. This keeps too many free hydrogen ions out of circulation in the urine and keeps the pH around 5 or 6; that allows more hydrogen ions to be eliminated as necessary.

The normal pH of ECF is 7.4; a range from 7.35 to 7.45 is considered normal. ECF pH below 7.35 is considered acidosis; pH above 7.45 is considered alkalosis. The body doesn't tolerate much variance in pH; you can only live a few hours with a pH below 7.0 or above 7.7; below 6.8 or above 8.0 is rapidly fatal. That's why the big deal with all the various ways to buffer ECF; there need to be many protections in place to assure that pH doesn't vary much from the normal range.

Acidosis. When the pH of ECF falls, it means there are excess hydrogen ions in the ECF. This sets up a concentration gradient so that the ions diffuse into cells. That messes up the electrical potential on the cell membrane—too many positive ions inside the cell—so potassium ions diffuse out of the cell to restore the electrical balance. That should work, but the problem is that once hydrogen ions get into the cell, they get neutralized by cell proteins. Now the cell shows a net loss of cations, because potassium left and hydrogen got neutralized.

The resulting imbalance of charge across the cell membrane makes it harder to for nerve cells to fire. The result is central nervous system depression, characterized by confusion, disorientation, and eventually coma.

When acidosis is caused by respiratory imbalance, we call it respiratory acidosis. This happens when the ventilation rate is insufficient to expel all the carbon dioxide produced by metabolic activity. When acidosis is caused by overproduction of organic acids, we call it metabolic acidosis. This can occur in a number of conditions: when cells carry on anaerobic fermentation too long, lactic acid can build up; in diabetes and alcoholism, ketones accumulate; when acid drugs, such as aspirin, are taken; and when bases are lost from chronic diarrhea or overuse of laxatives.

Alkalosis. In alkalosis the pH of ECF is too high; this means too few hydrogen ions. Now the concentration gradient causes hydrogen to diffuse out of cells, so potassium diffuses in to replace them. Now we've caused the cell membrane to move closer to the charge difference associated with firing. This makes the nerve cells are over excitable; and neurons fire spontaneously without receiving the usual stimulation. It leads to muscle spasms, muscle tetany, convulsions, and respiratory paralysis.

When alkalosis occurs because of respiratory imbalance, we call it respiratory alkalosis. This occurs in hyperventilation. Metabolic alkalosis isn't very common and is usually associated with loss of stomach acid, either because too much bicarbonate is taken or due to chronic vomiting.

Compensated imbalances are temporary conditions that are fairly quickly corrected by physiologic and chemical buffer systems in the body. Uncompensated imbalances are those the body can't or doesn't correct. We have a number of compensation mechanisms.

Respiratory Compensation. The respiratory system can adjust the partial pressure of carbon dioxide in ECF. We've already talked about how increased carbon dioxide (from decreased ventilation) lowers pH and increased carbon dioxide raises pH. We've also talked about how an increase in carbon dioxide, hypercapnia, stimulates increased ventilation and how a decrease in carbon dioxide, hypocapnia, reduces ventilation.

This works pretty well for conditions caused by abnormal levels of carbon dioxide, but not so well for other conditions. Adjusting ventilation rate can compensate somewhat for higher or lower levels of acids, adjusting a pH two or three tenths of a point, but nor much more than that.

Renal Compensation. The kidneys work slower, but have a far greater buffering capacity. That means they're not much use for short-term pH imbalances, but they're very effective in the long-run. Kidneys simply secrete more hydrogen ions during acidosis, buffering the resulting urine to keep the pH above a critical level, and secrete bicarbonate ions during alkalosis, which makes them unavailable to bind hydrogen ions and lowers pH.

That's it for Chapter 24. Now you can use your objectives to build a study guide for this chapter. When you're confident you've learned the information in the chapter and understand the concepts presented here, request a test via e-mail.