Fluids and Electrolytes

Chapter 3 in textbook

Unit Learning Objectives

• Describe the mechanisms that normally regulate water balance

• Explain in detail how both aldosterone and ADH secretion are regulated and the specific function each hormone plays in maintaining water balance

• Explain in detail normal fluid dynamics through the capillary wall (the forces that contribute to fluid exchange between the ICF and ECF).

• Interpret the effect of a change in one of the forces on the movement of water

• Explain the four mechanisms that can produce edema

• Name and describe water, sodium, and potassium imbalances in the body

  • • Describe how each of these imbalances alters normal physiology

    • Describe the hormonal responses that help maintain water and electrolyte balance

• Differentiate between isotonic, hypotonic, and hypertonic solutions and the cellular effects of each

• Define pH and the factors that determine blood pH

• Explain how the carbonic acid-bicarbonate system is affected by the renal and respiratory systems.

  • • Differentiate between compensation and correction

• Define and compare acid-base imbalances

  • • Explain causes and describe how each of these imbalances alters normal physiology

• Explain in detail how pH compensation and pH correction occur for each of the 4 primary pH imbalances.

  • • List expected pH, carbon dioxide, and bicarbonate for metabolic disorders that have been compensated

• Analyze data and predict whether a person has acidosis or alkalosis (metabolic or respiratory)

Overview

Fluid, electrolyte, and pH imbalances are common to many disease processes. For this reason, this information is critical to understanding many disease process that you'll learn about throughout the remainder of this course.

Let's begin with fluid imbalances, and specifically the mechanisms of two hormones, ADH and aldosterone. There is a brief review of these two hormones below, but you should completely review these two hormones so that your understanding is thorough.

Before you begin this chapter, a thorough review of kidney structure and function is very important. An overview of kidney function is provided in the video below. Later in the course you will spend a great deal more time on kidney function and alterations to kidney function.

As usual, there are "Thinking questions" and other questions embedded in the notes. For some, answers are provided by following the "A:" link after the question. You should always try and answer the question(s) before seeking out the answer. Additionally, some questions do not have an answer provided. You need to think through these questions carefully. If you find yourself getting stuck, be sure to seek out input from your classmates, and then your instructor.

Fluid and Electrolyte Balance

Water is incredibly important to the body, and so proper regulation of water balance is essential. The body has hormones that play a major role in properly regulating water in the body.

Regulation of water balance

Water balance is regulated by thirst perception and the antidiuretic hormone (ADH).

Thirst perception regulates water balance

Dry mouth, decrease plasma volume, or hyperosmolality (excess salts per volume of plasma) activate osmoreceptors in the hypothalamus, which cause the sensation of thirst. The sensation of thirst then stimulates water-drinking behavior (and thus water intake), which will increase plasma volume and decrease the concentration of solutes (decrease osmolality).

Anti-diuretic hormone (ADH)

ADH is produced by the hypothalamus and stored and secreted by the posterior pituitary. The renal tubules are the target of the hormone's action. ADH increases water reabsorption by the renal tubules.

What does the term reabsorption refer to? A:

ADH secretion decreases blood osmolality (for our purposes, osmolality and osmolarity can be used interchangeably, both deal generally with the concentration of solutes in the solvent, just how precisely the concentration is measured varies), as more water is reabsorbed into the blood, the concentration of solutes is reduced.

There are three different physiologic triggers that cause the release of ADH. These triggers are:

• • 1. decreased blood pressure

    2. increased blood osmolality

    3. decreased blood volume

Each of these triggers act independently. Consequently, decreased blood volume will trigger the release of ADH even if blood pressure is normal. Or, for example, increased blood osmolality will stimulate the release of ADH even if blood volume is normal.

Keep in mind that with few exceptions, hormones work on a negative feedback system. That means that increased blood pressure, decreased blood osmolarity, and increased blood volume all normally inhibit the release of ADH.

Regulation of ADH secretion is summarized in the image below.

Aldosterone

The second hormone involved in regulation of fluid balance is aldosterone. A brief review of the hormone is provided below. Be sure that you understand this hormone thoroughly. A basic physiology text is ideal for review of this hormone.

The hormone aldosterone is produced and secreted by the adrenal cortex. As with ADH, the renal tubules are the target tissue. Aldosterone, however, has a different action than ADH. The biological role of aldosterone is to increase sodium reabsorption. Because of osmosis, water in the filtrate follows the reabsorbed sodium, so consequently aldosterone secretion also increases water reabsorption.

The release of aldosterone is complex. Kidney perfusion is determined by both blood volume and blood pressure to the kidney. Decreased kidney perfusion results in the release of renin by the kidneys. Renin is one of the enzymes necessary for synthesis and activation of angiotensin from its inactive form. Once activated, angiotensin stimulates the synthesis and release of aldosterone from the adrenal cortex. In a round about way, decreased kidney pefusion eventually results in the release of aldosterone.

Aldosterone has another function as well. The "doorways" in the renal tubules that are opened by the action of aldosterone, also serve as a route for K+ secretion AND H+ secretion. Potassium ions (K+) and hydrogen ions (H+) compete for the same doorway. Notice in the figure that secretion occurs in the opposite direction of reabsorption. Tubular secretion is the process that moves substances from the blood and into the filtrate.

Natriuretic peptides

These are hormones triggered for release by high blood volume/blood pressure. They lead to an increase in sodium and water excretion by the kidneys, which lowers blood volume and blood pressure (they do this in part by inhibiting the function of aldosterone). They work in an antagonistic fashion to both ADH and aldosterone.

Next, let's look at some basics of fluid in various body compartments.

Fluid Balance in body compartments

1. Extracellular Fluid (ECF) is ALL fluid outside of cells and includes interstitial fluid (not in vessels) and plasma (in vessels).

The primary cation (positively charged atom or molecule) of ECF is Na+; the primary anions (negatively charged atom or molecule) are Cl-, HCO₃- (bicarbonate).

2. Intracellular Fluid (ICF) is ALL fluid inside of cells. Most (70% of all body fluid) is located inside of cells.

The primary cation is K+; the primary anions are HPO₄- (phosphate) and proteins. Although we don't typically think of proteins as being "charged", because they are composed of amino acids, protein molecules can deprotonate (lose a proton or H+) and become negatively charged.

Now that we have reviewed the basics, let's take a look at two fluid imbalances.

Both of these fluid imbalances are referred to as "isotonic" because the blood osmolarity is normal. The "imbalance" refers to the volume of fluid — either too little fluid (hypovolemia) or too much fluid (hypervolemia).

Isotonic fluid imbalances

• • Hypovolemia is an isotonic fluid imbalance characterize by too little fluid in the blood. It is generally caused by loss of isotonic fluid, such as blood loss or intestinal fluid loss.

    • Consequences of hypovolemia are:

      1. Tachycardia

      2. Decreased urine output

      3. Possible change in blood pressure. Hypovolemia can lead to decreased blood pressure. However, blood pressure could remain normal.

         1. • How does the body maintain blood pressure despite blood loss? A:

• • Hypervolemia is an isotonic fluid imbalance characterized by too much fluid in the blood. Causes of hypervolemia include excessive administration of IV fluids and excessive levels of aldosterone (hyperaldosteronism). Hyperaldosteronism is quite common in many disease processes.

Consequences of hypervolemia included:

• • • 1. decreased HCT (hematocrit)

         • HCT is the percentage of volume of blood that is composed of red blood cells

      2. increased BP

      3. edema

      4. weight gain

      5. jugular vein distention

The image below shows how hematocrit is determined. If there is excessive fluid in the blood, then proportionally there will be fewer packed cells, and therefore, HCT is decreased.

Hypervolemia is also quite common in heart failure patients. The term heart failure refers to the heart losing its pumping ability. (Heart failure and heart attack are two different things.)

When the heart loses its pumping ability, what happens to kidney perfusion (the amount of blood that gets to the kidney? It decreases.

This change in kidney perfusion ultimately (via renin-angiotensin) leads to elevated aldosterone. For heart failure patients, a sudden increase in weight often means that their hearts are not pumping adequately. For that reason, heart failure patients are advised to weigh themselves daily as a simple means of assessing heart function and kidney perfusion.

You'll learn much more about this later on in the course.

The next topic that you'll cover is mechanisms of edema. Before you learn about the specifics of edema, you'll start by reviewing fluid movement across capillary membranes.

Movement of fluids through capillaries

There are four different pressures that determine fluid movement across capillary walls:

1. Blood hydrostatic pressure (BHP)

   • This force is exerted by blood on vessel walls

   • This force favors filtration out of the capillary

The image below shows a capillary and BHP favoring filtration (movement out of capillaries into the interstitium).

2. Blood oncotic pressure (BOP)

• • This pressure is exerted by proteins in the blood. Oncotic pressure is NOT the same as osmotic pressure. Osmotic pressure is exerted across a cell membrane and results from the presence of ions, like Na+.

  • BOP opposes filtration of fluid out of the capillary. You can think of it as if the proteins are trying to pull fluid back into the capillary. This is the only pressure, of the four, that opposes filtration.

In the image below, BOP has been added, with an arrow directed inward showing that BOP opposes filtration.

3. interstitial fluid oncotic pressure (IFOP) or simply IOP

• • This pressure is exerted by proteins in the interstitium. These proteins have leaked out of the capillaries or are proteins synthesized and exported by surrounding cells.

  • These proteins pull fluid out of the capillary so this pressure favors filtration out of the capillary

In the image below, proteins in the interstitium favor filtration.

4. Interstitial fluid hydrostatic pressure (IFHP) or IHP.

• • This is negative pressure exerted by fluid in the interstitium

    • This is a very small force, and has little impact on filtration (but would have a small effect on favoring filtration)

    • Instead, its main role is to prevents capillaries from collapsing

See the image below of IHP.

The net effect of all these pressures is that at the arterial end of the capillary, fluid leaves the capillary and enters the interstitial spaces. At the venous end of a capillary, 90% of the fluid is returned to the capillary. What happens to the remaining 10% of fluid?

It is drained by the lymphatic system and eventually returned to the blood. Please review the lymphatic system if you're unfamiliar with it.

The image below from your textbook summarize the filtration pressures. Notice that the major driving forces for filtration and reabsorption are the forces inside the capillary, the blood, or capillary, hydrostatic pressure and the blood, or capillary, oncotic pressure.

Alterations in Water Movement: Edema

In this section you'll learn about edema, which is the accumulation of fluid in interstitial spaces.

Edema results from changes in one or more of the pressures that determines fluid dynamics across a capillary wall. So, in this course, when thinking about edema, think about what capillary force change is resulting in the edema. There are four different mechanisms of edema. Each will be discussed below:

1. Decreased BOP

The first mechanism causing edema is decreased BOP. Remember that oncotic proteins act to oppose filtration. So, if there are fewer proteins in the blood, there are fewer proteins to oppose filtration. That means the more fluid will move out of a capillary at the arterial end and less fluid will be returned at the venous end; the net result is fluid accumulation in the interstitium.

• • • Causes

      • What would cause BOP to decrease? Think back to where these oncotic proteins are made. Under what circumstances, then, would the body be unable to make enough oncotic proteins?

        • Liver diseases such as cirrhosis affect the body's ability to synthesize the plasma proteins (like albumin) that provide most of the oncotic pressure.

In addition to liver disease, the body is also unable to synthesize adequate proteins when the liver doesn't have the "ingredients" for protein synthesis. Proteins are built from amino acids. In case of severe protein malnutrition, the liver can't make sufficient oncotic proteins, and edema commonly results.

In addition to decreased synthesis of oncotic proteins, BOP also is decreased when the body loses excessive amount of proteins. Normally, proteins are not filtered out of the glomerulus and into the glomerular (or Bowman's) capsule (they are too large). But, what would happen if the glomerulus became more permeable (the pores got larger)?

Proteins would leak out of the blood and into the filtrate. This increased permeability can result from an inflammatory response, as you will learn about in the next module.

So, BOP also decreases with various types of kidney diseases that result in inflammation of the glomerulus.

Later in this course, you'll learn more about these kidney diseases.

• • • Consequences

      • The consequences of decreased BOP are two-fold. First, filtration at the arterial end of the capillary is increased because there is less pressure opposing filtration. Second, reabsorption at the venous end of a capillary is decreased because there is less pressure drawing fluid back into the capillary. Fluid accumulates in the interstitial, and there you have it .... edema.

2. Increased BHP

The second mechanism of edema is increased BHP.

• • • Causes

      • There are many causes of increased blood hydrostatic pressure, including

        • hypertension

        • hypervolemia

        • renal failure (fluid accumulates in the blood because of decreased urine production)

        • venous obstruction (blood backs up behind the obstruction, raising BHP.)

• • • Consequences

      • The consequences of elevated BHP are exactly the same as those of decreased BOP.

Filtration at the arterial end of the capillary is increased because there is more force pushing fluid out of the capillary. At the venous end of the capillary, on the other hand, there is greater than normal force favoring filtration, and so reabsorption is less than normal. The end result is edema.

3. Increased capillary membrane permeability

• • • The third mechanism of edema is increased capillary membrane permeability. In the chapter on inflammation you will learn more about the many chemical mediators that cause increased capillary membrane permeability.

      • How does this change in permeability cause edema? It's all about proteins.

If you look at the image below you'll see a membrane with small pores in it. A capillary membrane has small pores in it that allow some molecules to leave the intravascular space and enter the interstitial space. Only small molecules (including some small proteins can pass through the pores).

Histamine, and other chemical mediators of inflammation, increase pore size, which allows larger proteins to leave the intravascular space and enter the interstitial space.

The result is that BOP decreases (because proteins leave the blood) and IOP increases (because more proteins enter the interstitium). Remember that BOP opposes filtration; IOP favors filtration.

• • • Causes of increased capillary membrane permeability

1. inflammation

2. allergic reactions

• • • Consequences

As BOP decreases and IOP increases, there is a net increase in forces favoring filtration, so at the arterial end of a capillary, more fluid than normal leaves the vessel and enters the interstitium.

At the venous end, less fluid is reabsorbed. And once again, the end result is edema.

4. Lymphatic obstruction

Lymphatic obstruction is the last mechanism of edema. Let's look briefly at the lymphyatic system.

One of the functions of the lymphatic system is collect interstial fluid (the 10% that's not reabsorbed into blood) and return it to the blood. This fluid has proteins in it (these proteins are what exerts IOP). The lymph capillaries collect the fluid and proteins and the fluid passes through a series of vessels and lymph nodes.

If lymph nodes are obstructed or removed, then the return of lymphatic fluid to the blood is blocked.

The interstium then accumulates fluid and proteins, consequently IOP is increased.

In either case (obstruction or removal), the consequence is that IFOP is increased. There is more filtration of fluid at the arterial end of a capillary and less reabsorption of fluid at the venous end. The end result, in some cases, can be quite devastating. You can read more about elephantiasis here.

The image below summarizes all four mechanisms of edema. Each of the mechanisms is in a lavender box. In the image, please note that blood oncotic pressure is referred to as capillary oncotic pressure. IOP is referred to as tissue oncotic pressure (which is a bad name because the proteins are in the interstitium, not in tissues).

Treatments for edema

Treatments for edema include:

• Elevation of the edematous limbs (for example, raising up the legs for a dependent edema)

• Use compression stockings or devices (to push fluids against gravity)

• Avoid prolonged standing

• Restrict salt intake

• Take diuretic agents (these have the opposite effect of ADH, the cause you to excrete more fluid)

Electrolyte imbalances are very common in disease process. In this section you'll learn about imbalances to two different electrolytes (imbalances of other electrolytes are possible, of course).

Electrolyte Imbalances

Let's start with a case study involving an electrolyte imbalance:

Sodium Imbalances

• • metabolic roles of sodium: sodium plays a key role in conduction of nerve impulses and is critical in maintaining water content of cells.

Hyponatremia

Hyponatremia is a condition in which sodium levels in the blood and interstitial fluid are lower than normal.

• • Causes of hyponatremia include:

    • depletional loss — excessive loss of sodium via sweating, urine, vomiting, or diarrhea. Urine loss of sodium can be the result of using excessive diuretics (a diuretic is any substance that promotes diuresis, the increased production of urine).

    • dilutional hyponatremia — sometimes it's not excessive sodium loss, but instead, excess total body water (TBW) relative to sodium. The excessive water volume is diluting out the sodium concentration.

Dilutional hyponatremia can be caused by the excess of a particular hormone:

Quick review: What would cause excessive ADH to be secreted? If you can't remember the triggers for ADH release, now would be a good time to go back to the beginning of this chapter.

It's appropriate for ADH to be released when blood becomes more hypertonic (or more salty). It's inappropriate for ADH to be released when blood is not hypertonic. The Syndrome of Inappropriate ADH release (SIADH) occurs when ADH is released when the blood is not hypertonic. When the blood has a normal tonicity (the right amount of saltiness, so to speak), the release of ADH can dilute out the salt causing hyponatremia.

Dilutional hyponatremia can also be from drinking too much water! And it can be deadly.

"Hold your wee for a Wii Contest" is an example of that. So is this story.

• • • Lack of intake — although uncommon, it is possible for an individual to consume too little sodium and, consequently, hyponatremia results. Typically this would occur with severe malnutrition.

• • Consequences of hyponatremia:

How does hyponatremia affect the body?

Sodium is an important ion in regulating osmosis. If you've forgotten what osmosis is, review the video below.

Remember that water follows salt. When blood and interstitial fluid (ECF) become less "salty" than normal, water moves from the less salty place (ECF) to the more salty place (ICF). Cells, and in particular neurons, fill with water. The results can be deadly.

Clinical features associated with hyponatremia are:

Intracranial swelling, seizures, and coma.

The next video shows red blood cells in a various tonicity solutions. The clip opens with the erythrocytes in normal saline (isotonic), then the solution becomes hypertonic, goes back to isotonic, and finally becomes hypotonic. Watch what happens to the cells in each condition.

Hypernatremia

Hypernatremia is either a sodium gain or excessive water loss in the ECF. The ECF becomes hypertonic to the ICF.

• • Causes

    • Excessive sodium gain — this can result from excessive IV salts, excessive consumption of salt, or sea-water near-drowning

More hazing hazards - too much soy sauce

• • • Excessive water loss — if too much water is lost, the sodium in the ECF becomes more concentrated.

Excessive water loss can occur from:

• • • • A fever (high metabolic rate spends more water).

        • If a person's body temperature is elevated to 102 degrees F, their water input should be increased by an extra 500 ml/day. With temperature elevations between 102 to 104 degrees F, their water intake should be increased by an extra 1000 ml day. Over 104 degrees F, an extra 1500 ml/day.

      • Hyperventilation (there is water vapor in exhaled air)

• • • • Lack of ADH (diabetes insipidus)

      • severe burns (one of the jobs of the epidermis is to hold water in the body)

• • • Insufficient water intake — this is seen most commonly in elderly who are physically unable to respond to thirst because of mobility problems or who have altered consciousness (as in Alzheimer) and are not aware of their thirst.

• • Consequences of hypernatremia

Water shifts from the ICF to the ECF and cells begin to shrink. Once again, water follows salt. Cells become dysfunctional as they lose water, particularly those in the central nervous system.

Early hypernatremia is manifested as lethargy and weakness, which can aggravate hypernatremia because an individual is less likely to drink water when feeling lethargic.

As hypernatremia progresses, seizures can result. In addition, body temperature begins to rise as the body's cooling system is depleted.

Remember from the video above what happens to cells in a hypertonic solution. The cells begin to shrink as water moves out of the cells into the ECF.

Potassium Imbalances

• • metabolic roles of potassium

Potassium is the primary cation in ICF.

People are like bananas. Banana cells are rich in potassium; people cells are rich in potassium.

When the body makes new cells, potassium moves into those cells. People who are making lots of cells need lots of potassium.

On the other hand, when cells are damaged, potassium spills out of the cells. When cells are sloughed, potassium is lost.

Where are two places in the body where cells are sloughed on a daily basis? A:

Potassium uptake by cells requires insulin and ATP (the Na/K+ pump is driven by ATP). Not surprisingly, insulin-dependent diabetics can face some interesting changes in their potassium levels.

In the absence of potassium intake, deficits occur within 2 - 3 days. The body doesn't have a very good mechanism for saving potassium.

Potassium is also excreted by the kidneys. Tubular secretion of potassium is regulated by aldosterone: along with the increased Na+ reabsorption with aldosterone, there is increased K+ secretion by the renal tubules. This would be a good time for you to review both nephron function and aldosterone again.

K+ secretion is also flow-dependent: increased flow, increased secretion. Many diuretics increase flow rate through the renal tubules. This is why many individuals who are prescribed diuretics, also take potassium supplements (or they are prescribed a potassium-sparing diuretic).

Hypokalemia

Hypokalemia a potassium imbalance in which the level of potassium in the ECF is lower than normal. The suffix "emia" always refers to blood. The decreased levels can be actual (K+ has been lost from the body) or relative (no loss in total body K+, but the K+ has shifted from the ECF to the ICF). For example, if insulin was administered to a person with normal potassium levels (normokalemia), the K+ in the ECF would shift into the ICF. If the levels of K+ in the blood was measured, it would be lower than normal.

• • • Causes of hypokalemia

The most common cause of hypokalemia is an ECF volume deficit. This volume deficit typically results from vomiting or diarrhea, or nasogastric suctioning.

So, what's the connection — how does a volume deficit cause hypokalemia. Hmmmm.... which hormone is involved here? Undoubtedly one of my two faves, either ADH or aldosterone?

Which one? A:

If a person has some sort of a stomach bug that causes vomiting, they are at risk for developing hypokalemia in a fairly short period of time. There is lack of intake AND their kidneys actively secrete the potassium because of increased aldosterone.

Hypokalemia can also result from using (some) diuretics in the absence of a K+ supplement.

Eating too much black licorice (not red, only black). As it turns out, a chemical in black licorice has an aldosterone-like effect. Too much aldosterone-effect.

Relative hypokalemia results from insulin administration and new tissue formation.

• • Consequences of hypokalemia

When the level of potassium in the ECF decreases, the most significant effect is on the resting membrane potential of neurons.

Hypokalemia decreases the resting membrane potential. As a result of this change in K+ levels, neurons require a stronger stimulus to initiate a response (an action potential) compared to when there is a normal amount of K+ in the ECF.

• • Clinical Manifestations of hypokalemia

All of the clinical manifestations result from neurons that are not generating nerve impulses (action potentials) as needed.

By system, the following clinical manifestations are typical of hypokalemia:

• • • CNS and neuromuscular: fatigue, CNS depression, muscle weakness

    • GI: decreased motility - nausea, vomiting

    • Respiratory: weak respiratory muscles, shallow respiration.

    • Cardiovascular: dysrhythmias, changes in EKG's. The figure below shows an EKG with normal potassium and an EKG with hypokalemia. The most noticeable change is the shallow T wave.

Hyperkalemia

Hyperkalemia is defined as elevated potassium in the blood.

• • • Causes of hyperkalemia

The primary causes of hyperkalemia include:

• • • • • decreased potassium secretion by the renal tubules. This occurs as a result of renal failure or adrenal insufficiency, i.e. not enough aldosterone.

        • extensive tissue damage. Remember that cells are rich in potassium. When they break they spill their potassium into the surrounding fluid.

        • insulin deficit.

          • • Can you explain why? A:

        • acidosis

• • • • • • As you will see in the next section, H+ ions move K+ ions out of cells when they move into cells.

• • • Consequences of hyperkalemia

Hyperkalemia has the opposite consequences of hypokalemia. With hyperkalemia, nerve impulses (action potentials) are generated too easily. However, muscles become fatigued as they are over-stimulated.

• • • Clinical Manifestations

      • • Neuromuscular system: muscle weakness

        • GI system: nausea and diarrhea

        • CV system: dysrhythmias, ventricular fibrillation, and cardiac arrest.

          • • An injection of KCl is lethal. In fact, KCl is one of the substances used in carrying out death sentences by lethal injection because it causes cardiac arrest.

The next section of this chapter focuses on acid-base balance, how the body maintains the correct pH, what can cause imbalances, how the body responds to acid-base imbalances, and how to use blood gas values to diagnose pH imbalances.

Acid-Base Balance