He huewai ola ke kanaka na Kāne.

Man is Kāne’s living water gourd.

Water is life and Kāne is the keeper of water. To dream of a well-filled water gourd that breaks and spills its contents is a warning of death for someone in the family.

ʻŌlelo Noʻeau, compiled by Mary Kawena Pukui, #598

Introduction

Figure 26.1: Drinking from a coconut

Homeostasis, or the maintenance of constant conditions in the body, is the fundamental property of all living things. In the human body, the substances that participate in chemical reactions must remain within a narrow range of concentrations. Too much or too little of a single substance can disrupt bodily functions. Metabolism relies on reactions that are all interconnected and any disruption might affect multiple organs or even organ systems. Water is essential to life. The physiological and cultural importance of water in life is also found in multiple places and people in Hawaiʻi named Waiola, literally “water of life” (wai = water, ola = life). Water does many things in our bodies — it serves as a solvent that dissolves and suspends the molecules found within our body, forms the basis of aqueous solutions that carry out metabolic processes, and transports heat, molecules, and cells throughout our body. The interactions of various aqueous solutions — solutions where water is the solvent — are continuously monitored by a large suite of interconnected feedback systems in your body. Understanding how the body maintains these critical balances are key to understanding good health.

26.1 Fluids & Fluid Compartments

Chemical reactions in your body that use water as a solvent are called aqueous solutions. Solutes are substances dissolved by water in the fluids of our body. Solutes vary in concentration in different parts of the body and include a wide variety of substances, including proteins, carbohydrates, and electrolytes. An electrolyte is a mineral that carries an ionic electrical charge. For example, sodium ions (Na+) and chloride ions (Cl-) are electrolytes. Electrolytes easily dissolve in water due to the polarity of water molecules.

Osmosis is the process in which water travels across a semipermeable cell membrane that separates two fluids and results in an overall movement of water toward the fluid that has a higher solute concentration. Osmosis will continue until the overall solute concentrations between the two fluids are equal, or if the movement of water by osmosis is counteracted by other forces and pressures affecting those fluids. Osmosis is a critical concept in understanding how fluids are distributed and balanced throughout the body.

Body water content

Water makes up a large component of your body’s mass and volume. The amount of water in your body, or body water content, changes throughout the day as you drink, eat, breathe, sweat, and go to the bathroom. Our body water content also changes during our life cycle, ranging from about 75% of body mass in infants, to about 50 to 60% in adult men and women, to as low as 45% in old age.

Different tissues have different water content (see figure 26.2). For example, your brain and kidneys have the highest water content (80-85% of their mass), and teeth have the lowest water content (8 to 10%). Skeletal muscle has a relatively high water content (70 to 75%), whereas white adipose tissue (white fat) has a low water content (about 10%). Therefore, someone who has a high percentage of muscle mass, like a bodybuilder, would have more body water content than someone who has a high percentage of white adipose tissue (body fat percentage), even if they have the same mass and height. The different water content of different tissues is also why, as we grow and age, our tissues and overall body composition change along with us, which is another reason that body water changes throughout our life.

Figure 26.2:  Water Content of the Body’s Organs and Tissues, with white adipose tissue (10%) (modified from OpenStax)

Fluid compartments

When describing the distribution of fluids throughout your body, they can be thought of as belonging to fluid compartments. Be careful to note that fluid compartments are not anatomical compartments, but rather describe the ways fluids and their solutes are distributed in your body and the differences in their overall content.

All the fluids in your body can be classified as either:

• Intracellular fluid (ICF) includes all the fluid found within the plasma membrane of all cells of your body.
• Extracellular fluid (ECF) includes all fluids located outside of a cell and are not found within the plasma membrane of any cell. ECF includes interstitial fluid and plasma.

Figure 26.3: Fluid Compartments in the Human Body: The intracellular fluid (ICF) is the fluid within cells. The interstitial fluid (IF) is part of the extracellular fluid (ECF) between the cells. Blood plasma is the second part of the ECF. Materials travel between cells and the plasma in capillaries through the IF. (from OpenStax)

Intracellular fluid (ICF)

Intracellular fluid (ICF) collectively describes the fluid within the plasma membranes of all the cells in your body. ICF is about two-thirds, or 60-65%, of the total water content in your body. In an adult male about 175 cm, 70 kg (5 ft 9 in, 155 lbs), ICF accounts for about 25 liters (seven gallons) of fluid [Figure 26.4]. This fluid volume tends to be very stable because individual cells have a very tiny amount of fluid on average (about 80-100 femtoliters; 1 femtoliter = 10-15 L); therefore, changes in cell water content would drastically affect a cell’s solute and enzyme concentrations. If there is not enough water content inside a cell, the cytosol becomes too concentrated with solutes to carry on normal cellular activities; if too much water enters a cell, the cell may burst and be destroyed (a process called lysis).

Extracellular Fluid (ECF)

Extracellular fluid (ECF) accounts for the other one-third or about 35-40% of the body’s total water content. The majority of ECF is found within the plasma and interstitial fluid. [Figure 26.4]

Plasma is the fluid portion of the blood that includes everything in the blood that is not a formed element, and approximately 20% of the ECF is found in plasma. Plasma travels through the circulatory system and transports various materials, including blood cells, proteins, electrolytes, nutrients, gasses, and wastes. Interstitial fluid (IF) collectively describes all the fluids surrounding the cells of your body but does not include plasma found inside blood vessels and the heart. Although IF does not circulate within vessels like plasma, IF still provides a route for gasses, nutrients, and waste materials to travel between cells and plasma. The IF is separated from the ICF inside cells by a selectively permeable cell plasma membrane that helps regulate the passage of materials between the IF and the interior of the cell.

The body has other water-based ECF that make up a relatively small portion of the ECF and total body water called transcellular fluid. [Figure 26.4] These “other fluids” include: the cerebrospinal fluid (CSF) that bathes and circulates the brain and spinal cord; lymph found within lymphatic vessels; synovial fluid that lubricates joints; pleural fluid in the pleural cavities surrounding the lung; pericardial fluid in the cardiac sac around the heart, peritoneal fluid in the peritoneal cavity of the abdomen, and the aqueous humor of the eye. Although relatively small in volume, because these fluids are located outside of cells, these fluids are also considered components of the ECF compartment.

Figure 26.4: A Pie Graph Showing the Proportion of Total Body Fluid in Each of the Body’s Fluid Compartments Most of the water in the body is intracellular fluid. The second largest volume is the interstitial fluid, which surrounds cells that are not blood cells. (OpenStax)

Composition of Body Fluids

Both major types of ECF, plasma and IF, differ significantly from ICF in their electrolyte balance (Figure x. compartments. electrolytes). Blood plasma and IF have higher concentrations of sodium, chloride, calcium, and bicarbonate compared with ICF. In contrast, the ICF has higher concentrations of potassium, phosphate, magnesium, and protein than blood or plasma. Although plasma and IF are similar in their electrolyte content, plasma has a much higher protein content than IF, as large proteins such as albumin do not filter out from blood vessels into the IF. The plasma proteins are responsible for generating the colloid osmotic pressure of blood plasma which helps to maintain the balance of water between the interstitial fluid compartment and the blood plasma.

Figure 26.5: The Concentrations of Different Elements in Key Bodily Fluids (OpenStax, edited to match correct Ca2++ information from Tortora/Martini)

Solute Movement

One vital concept you should take from this section is that the electrolyte and protein content is not the same between the inside and outside of a cell. These differences, or concentration gradients, are needed for processes that move water, such as diffusion, osmosis, and oncotic pressure.

Knowing the differences between ECF and ICF electrolyte content will also help you to predict how electrolytes will flow if their respective ion channels open. When an ion channel opens, ions that can pass through that channel will generally flow from higher to lower concentrations. For example, if sodium ion channels open in a cell at rest, sodium will flow from the IF into the ICF of the cell until the differences in sodium concentration and electrical charge on both sides of the cell membrane are balanced. The movement of sodium ions through an ion channel is an example of facilitated diffusion because, usually, ions cannot diffuse across a nonpolar phospholipid membrane by themselves due to their charge, but the ion channels facilitate their movement across the membrane. This example is also a type of passive transport, as it occurs without the use of additional energy or ATP once the ion channels are open. This concept is crucial to understanding action potentials in muscle cells and neurons.

Concentration differences in electrolytes are maintained by pumps and transporters that use active transport by taking energy from ATP or energy stored in the concentration gradients to move electrolytes between the ICF and ECF. An example of this transport are sodium-potassium pumps. These pumps use the energy from ATP to pump sodium out of the cell and potassium into the cell, which is the major reason why there is more sodium in ECF and more potassium in ICF (Figure x.compartments.transport).

Facilitated Diffusion: Facilitated diffusion of substances crossing the cell (plasma) membrane takes place with the help of proteins such as channel proteins and carrier proteins. Channel proteins are less selective than carrier proteins, and usually mildly discriminate between their cargo based on size and charge. (adapted from OpenStax)

The Sodium-Potassium Pump The sodium-potassium pump is powered by ATP to transfer sodium out of the cytoplasm and into the ECF. The pump also transfers potassium out of the ECF and into the cytoplasm. (credit: modification of work by Mariana Ruiz Villarreal) (from OpenStax)

Figure 26.6: Compartments Transport

26.2 Water Balance

Control of Body Water Content

The average adult takes in about 2.5 liters (almost 3 quarts) of fluids each day. Although most of the fluids are absorbed through the digestive tract, about 230 mL (8 ounces) per day is generated from metabolic processes within our cells. Additionally, about the same volume (2.5 liters) of water leaves the body, most of it is removed as urine. The kidneys are the primary regulators of water loss and overall body water content. A small amount of water is also lost through other routes such as evaporation from the skin and air expelled from the lungs.

Figure 26.7: Ahupuaʻa of Oʻahu

Regulation of Body Water Gain

Drinking fluids is considered a voluntary process since you make conscious efforts and decisions about whether or to do so. But how does your body let you know you need to drink and aid in that decision to urge you to drink?

For example, say you are running the Honolulu Marathon or the ironman in Kona and are becoming dehydrated, which describes an overall net loss of water resulting in insufficient water content in blood and other tissues. As you breathe while running, you lose water from the inside of your respiratory tract. When you sweat to cool off, you also lose water from the water content of your sweat. If you urinate or defecate at a bathroom stall during the route, you also lose water through those excretions. All the water lost through these processes were ultimately extracted from blood plasma and the ECF surrounding your cells.

When you become dehydrated, the solutes in your blood become more concentrated, increasing plasma osmolality, which is the ratio of solutes to water in blood plasma. Your plasma osmolality value reflects your state of hydration and overall fluid content in your body’s tissues. Your body’s homeostatic mechanisms maintain plasma osmolality within a narrow range by regulating both water intake and output. The thirst center in the hypothalamus (link to hypothalamus section of CNS chapter) is a central structure in maintaining plasma osmolality homeostasis. Thirst is the desire and urge to drink water.

Osmoreceptors are sensory receptors in the thirst center in the hypothalamus that monitor the concentration of solutes (osmolality) in the blood. If plasma osmolality increases above its normal range, the hypothalamus transmits signals that result in conscious awareness of thirst and urges you to respond by drinking water or fluid. If you are dehydrated like in the marathon example, your increased plasma osmolality will also stimulate your hypothalamus to release antidiuretic hormone (ADH) from the posterior pituitary gland. ADH signals the kidneys to recover more water from urine. This conserved water is reabsorbed into the blood plasma, which dilutes it and lowers plasma osmolality. During dehydration, the hypothalamus also sends signals to the sympathetic nervous system, which sends signals to the salivary glands in the mouth. The sympathetic signals decrease the water content in saliva and result in a sticky feeling in your mouth due to the increased mucus concentrations. These changes in secretions result in a “dry mouth” and further increase the sensation of thirst. [Figure 26.8]

Dehydration also decreases overall blood volume due to the loss of water. As mentioned in the vasculature chapter (link to blood pressure section of vasculature chapter), blood volume is linked to blood pressure; therefore. decreased blood volume due to dehydration will cause a decrease in blood pressure. The decrease in blood volume will be detected as less stretching of the atrium due to lowered preload resulting in inhibition of release of atrial natriuretic peptide (ANP). Less ANP means less sodium and less water will be lost in the urine to restore blood volume. Additionally, the decreased blood pressure will stimulate baroreceptors to increase the heart’s activity to compensate, but it will also stimulate the kidneys to increase their production of renin resulting in more generation of angiotensin II. As mentioned in the endocrine and vasculature chapter (link to RAAS section of endocrine or vasculature chapter), angiotensin II has powerful effects on increasing blood pressure by stimulating vasoconstriction and also promoting the release of other hormones that increase blood pressure, such as ADH from the posterior pituitary and aldosterone from the adrenal cortex. Aldosterone will reduce sodium and water loss in the urine to help restore blood pressure by increasing blood volume. Angiotensin II also targets and stimulates the thirst center to urge you to drink more water, thereby increasing your overall body water content, and in turn, increasing the water content in your blood. After your intake of fluids, the wet sensations on your tongue and the stretch felt in your stomach once the fluid fills its volume will send signals that inhibit the hypothalamic thirst center, increasing your feelings of satiety and reducing thirst. This is also why eating a meal can also inhibit feelings of thirst, especially if the food has a lot of water content, for example, fruits, vegetables, poi, and soups.

Figure 26.8: A Flowchart Showing the Thirst Response The thirst response begins when osmoreceptors detect a decrease in water levels in the blood. (from OpenStax ]

Water is also generated by the metabolic activity in our cells. This amount is relatively small, with only 230 mL (8 ounces) being generated per day. Our cells generate water from the electron transport chain during the last step of aerobic respiration (link to ETC/aerobic respiration section of metabolism chapter). It also generates water in certain reactions such as dehydration synthesis reactions when creating polymers, such as glycogen, from monomers, such as glucose. This water, called metabolic water, is contrasted with preformed water, which refers to water molecules generated outside our body, such as the water we ingest through our food and drink.

Regulation of Body Water Loss

The urinary system is the primary controller of water loss from the body. A person produces an average of 1.5 liters (1.6 quarts) of urine per day. Although the volume of urine you produce changes in response to your hydration levels and water intake, you still need to produce at least a certain minimum amount of urine per day. This minimum necessary volume, also called obligatory water loss, of urine, is about 0.5 liters (~0.5 quarts) per day. This minimum volume is needed for the kidneys to flush out and excrete 100 to 1200 milliosmoles of solutes per day to maintain pH and to rid the body of excess salts and water-soluble chemical wastes, such as creatinine, urea, and uric acid. If you do not produce the minimum volume of urine, water-soluble metabolic wastes will start to accumulate in the tissues in your body, which can impair tissue and organ function. Other types of obligatory water loss include the loss of water in the air we exhale and the loss of water through evaporation from our skin.

The kidneys also must adjust if you drink too much fluid beyond what is needed for normal hydration. Any water loss above obligatory water loss is called facultative water loss. Excess hydration will stimulate diuresis, which is an increased production of urine above normal levels. Diuresis begins about 30 minutes after drinking a large quantity of fluid, reaches a peak after about one hour, and restores normal urine production after about three hours.

Even though you absorb most of the water you ingest through your small intestine and colon, you also lose a relatively small amount of water (150 mL, 5 ounces) in your feces each day. The water you lose through urination and defecation are considered types of sensible water loss because you are aware of these processes and how they remove water from the body. Water is also lost through the skin through evaporation from the skin surface and air expelled from the lungs (estimated 600-800 mL per day). This type of water loss is called insensible water loss because it occurs without you being aware.

Hormonal Control of Water Loss

Antidiuretic hormone (ADH), also known as vasopressin, is a peptide hormone produced by the hypothalamus and is released from the posterior pituitary when osmoreceptors in the thirst center detect increased plasma osmolality (see endocrine chapter: posterior pituitary section). ADH targets the kidney and increases the amount of water reabsorbed from the collecting ducts and tubules within the kidney. The overall effect of ADH is less fluid being lost through urine, and more water being retained in the body.

Aldosterone is a steroid hormone produced by the adrenal cortex and also targets the kidneys. Aldosterone targets the final stages of urine formation in the distal part of renal tubules and also in collecting ducts and causes the kidneys to reabsorb more sodium at the expense of potassium. Water follows the reabsorption of sodium due to osmosis; thus, the overall effect of aldosterone is increased water retention in the body and decreased sodium and water content in urine.

The renin-angiotensin-aldosterone system also regulates urine output. Angiotensin II further stimulates the production and release of both ADH and aldosterone, causing the reabsorption of more water and sodium from the filtrate in the kidneys. The overall effect of angiotensin II is to amplify further hormonal controls that retain water in the body and decrease water loss through the urine.

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are hormones that oppose the effects of ADH, aldosterone, and angiotensin II on water balance. ANP and BNP are produced in the atria and ventricles of the heart, respectively, and target the kidneys. As described earlier, when the heart detects increased blood volume through activation of stretch receptors, it releases ANP and BNP. The overall goal of ANP and BNP is to lower blood volume to bring it back to normal homeostatic levels. True to their name, ANP and BNP are natriuretic peptides, literally meaning that they increase the secretion of sodium (“natri-”) to form urine (“uresis”), where it is excreted along with additional water that follows the increased sodium levels in urine (due to osmosis). The overall effect of ANP and BNP is increased water loss from the body.

Movement of Water between Body Fluid Compartments

A fluid shift is the rapid movement of water and fluid volume between the fluid compartments of the body. Hydrostatic pressure and osmotic pressures are examples of regular physiological forces that trigger fluid shifts. A sudden change in fluid volume in one of the compartments can trigger fluid shifts to balance out the change and maintain homeostasis.

For example, in excessive bleeding and hemorrhage, blood pressure will severely drop, and interstitial fluids (IF) will shift into the intravascular space within vessels to bring up plasma volume and restore blood pressure so adequate perfusion to the brain and other vital organs are maintained.

During dehydration, your body may shift fluids from intracellular fluids to plasma to maintain your blood pressure and perfusion if your blood pressure is low. This is why your skin may appear dull or fine lines may appear if you are not sufficiently hydrated due to the reduced water content in your cells and connective tissues.

High blood pressures can cause fluid shifts that move fluid from the intravascular space and into the IF surrounding tissues. This is a common cause of edema and abnormal fluid accumulation in IF, especially in soft tissues.

Medical interventions can also use fluid shifts to restore homeostasis in water balance, especially disruptions in fluid volumes and pressures. Intravenous (IV) fluids are one way of altering the fluid volumes in the compartments of the body and adding solutes such as salts and sugars can help adjust levels of tonicity that will either move fluids into or out of ICF and ECF compartments based on osmotic pressure.

The GI tract can also be used to restore fluid balance, as the small intestine and colon can absorb water and move it into ECF. This can be accomplished through oral rehydration therapy that has solutes dissolved in water, such as that seen in coconut water. Enemas can also be used for rehydration by introducing fluids through the anus and into the rectum, where the water and solutes can be absorbed through the mucous membranes. However, if there are problems with the GI tract, such as vomiting or diarrhea, these methods may not be used as the additional fluids will not stay in the body. This is especially important because these are common causes of dehydration and oral rehydration will be ineffective.

Imbalances in Body Water

As mentioned earlier in this chapter, dehydration and having insufficient body water can affect solute concentrations and plasma osmolality in your body. A severe lack of water due to dehydration can harm the functioning of your cells, tissues, and organs. However, the opposite is also true — having too much fluid in your body can also be harmful to the normal functioning of your cells, tissues, and organs.

Water intoxication

Although it is crucial to maintain normal hydration levels, it is possible to overdo it. Drinking too much water at a rate that exceeds the rate that your body can excrete it can result in a condition called water intoxication (also, overhydration or hyperhydration). Increasing your water intake and your body’s water content will dilute the concentrations of solutes found in your ECF. This can alter the electrolyte concentration gradients and affect the transport of ions needed to cause action potentials in neurons. Having too much water in your ECF can also make it hypotonic relative to the ICF inside your cells, causing them to swell due to osmosis. This is dangerous and potentially life-threatening as it can affect the functioning of neurons in your brain, and also increase the overall pressure inside your skull (intracranial pressure). This increased pressure will impede the flow of blood to your brain, thus causing disorientation, confusion, and possibly death if homeostasis of pressure and water balance is not restored in time.

Edema

Edema is the accumulation of excess water in IF surrounding tissues. Recall that more fluid filters out of our capillaries every day than is reabsorbed back into our capillaries. This imbalance is corrected by returning excess fluid via lymphatic capillaries and vessels. Edema is caused by some sort of disruption that affects the blood or lymphatic capillaries that maintain this fluid balance between the plasma and IF.

Common causes of edema include: an underlying medical condition, pharmacological drugs, pregnancy, injury, or allergic reaction. Edema is most common in the soft tissues of the extremities with a lot of connective tissue and IF. In the limbs, edema may be seen as a swollen and puffy look with an increase in the size of the limb above normal, and a stretched, tight skin appearance. If a clinician suspects edema, they may check for subcutaneous edema by pressing a finger firmly into the suspected area and then releasing it. If the indentation made by the clinician’s finger remains for several seconds, it is called pitting edema.

Edema can also affect specific organs and affect their function. When excess fluid builds up in the air sacs of the lungs, it is called pulmonary edema. Pulmonary edema causes difficulty with breathing and sometimes chest pain due to the excess fluid slowing the diffusion of oxygen and carbon dioxide (CO2) between the alveoli and blood. There are multiple potential causes of pulmonary edema; however, generally, they involve something causing increased filtration of fluid from plasma to the alveolar air space, either due to a relative increase in hydrostatic pressure within pulmonary capillaries or a lack of colloid osmotic or oncotic pressure. Pulmonary edema is commonly seen in people with congestive heart failure (CHF). In left-sided CHF, excessive leakage of water into alveoli occurs because the left ventricle is not pumping enough blood. This decrease in cardiac output and flow means that fluids will accumulate in the chambers and vessels that eventually lead to the left ventricle. If we trace the blood flow backward from the left ventricle, we will reach the left atrium, pulmonary veins, and then the pulmonary capillaries. The increased volume left in the capillaries results in increased hydrostatic pressure within pulmonary capillaries, causing fluid to be pushed out of them and into lung tissues.

Other causes of edema include damage to blood vessels or lymphatic vessels, such as a traumatic injury that severs blood vessels or a tumor that compresses the lymphatics. This causes fluid to accumulate in tissues or impairs the return of excess IF into circulation. Edema can also occur in chronic or severe liver diseases such as cirrhosis, in which the diseased liver is unable to produce sufficient plasma proteins such as albumin. A decrease in albumins, globulins, and other liver proteins results in a decrease in colloid osmotic pressure, which decreases the amount of water reabsorbed back into capillaries, increases net filtration pressure, and can cause edema. Malnutrition involving insufficient protein intake, called kwashiorkor’s disease, would also prevent the liver from creating plasma proteins by eliminating the necessary amino acids. Plasma protein can also be lost in the urine in certain conditions such as nephrotic syndrome, which would have the same effect as the lack of production of plasma proteins by the liver.

Mild, temporary edema of the feet and legs may be seen in otherwise healthy people who sit or stand in the same position for long periods, such as a supermarket cashier or computer programmer who has a lack of breaks where they can move about. This mild edema occurs because skeletal muscle contractions in the legs help to circulate fluids in the deep veins and lymphatic vessels of the lower limbs to push fluids back to the heart. Thus, a lack of leg movement can result in reduced flow from the lower limbs and fluid accumulating in those tissues.

Medications that can result in edema include vasodilators, calcium channel blockers used to treat hypertension, non-steroidal anti-inflammatory drugs, estrogen therapies, and some diabetes medications.

Treatment of edema usually focuses on treating the underlying cause that led to edema. However, additional therapies can be recommended or prescribed to reduce the effects of edema, such as exercises to keep the blood and lymph flowing through the affected areas. Other recommendations could include elevation of the affected part to assist drainage back to the torso and circulation, massage and compression of the areas to move the fluid out of the tissues, and decreased salt intake to decrease sodium and water retention.

Ascites

Ascites is the accumulation of excess fluid within the peritoneal cavity of the abdomen. The peritoneum is a continuous sheet of serous membrane that consists of a layer that lines the inside of your abdominopelvic or peritoneal cavity (parietal peritoneum), which is continuous with a layer that wraps around organs inside your abdominopelvic or peritoneal cavity (visceral peritoneum). The peritoneum is a sac much like the pericardium around your heart and the pleura around each lung, and typically only has a small amount of fluid (50 to 100 mL). However, when fluid starts to accumulate between the parietal and visceral peritoneal layers, it results in a bloated and distended abdomen that swells due to the accumulation of fluid in the peritoneum. This can be detected as a fluid wave on physical examination. One cause of severe ascites is cirrhosis of the liver in which blood flow through the liver is impaired generating back pressure or hydrostatic pressure in the hepatic portal vein, called portal hypertension, causing the fluid to leak out into the cavity. This, together with impaired plasma protein production by the diseased liver resulting in reduced colloid osmotic pressure, creates two forces that cause fluid to move rapidly into the peritoneal cavity. This fluid puts pressure on the diaphragm making it difficult to breathe and the fluid must periodically be drained using a procedure called paracentesis.

Pericardial effusion

Pericardial effusion is the abnormal accumulation of excess fluid within the pericardial sac that surrounds the heart, which normally contains only 15 to 50 mL of fluid that lubricates the space between the visceral and parietal layers of the pericardial sac. The buildup of fluid in this area can restrict the movement of the heart due to the excess fluid pushing back against the heart as it tries to relax during diastole. This will eventually result in an overall reduced cardiac output due to less filling in the ventricles and reduced blood pressure from the reduced output. There are many possible causes of pericardial effusion, including infection, inflammation, trauma, cancer, and cardiovascular disease and injury but the overall effect of compression on the heart is called cardiac tamponade, and it can be fatal if the fluid is not drained using pericardiocentesis.

Pleural effusion

Pleural effusion specifically affects the lungs and is the abnormal accumulation of excess fluid within the pleural space between the parietal and visceral layers of the pleural membrane that surrounds each lung. Similar to the pericardial fluid around the heart, the lungs only have a small amount of pleural fluid (about 70 to 210 mL (2.4 to 7.1 oz) in an adult weighing 70 kg (~155 lbs). Pleural effusion will cause increased pressure and restricted movement of the lungs, and the symptoms can range from asymptomatic to shortness of breath, pain, cough, and fever if the pleura becomes inflamed (pleurisy).

26.3 Electrolyte Balance

The body contains a large variety of ions, or electrolytes, which perform a variety of functions. Some ions assist in transmitting electrical impulses along cell membranes in neurons and muscles. Other ions help to stabilize protein structures in enzymes. Still, others aid in releasing hormones from endocrine glands. All the ions in plasma contribute to the osmotic balance that controls the movement of water between cells and their environment. We will examine six of the most important of these electrolytes, including sodium, potassium, calcium, magnesium, phosphate, and chloride. [See Figure 26.5: The Concentrations of Different Elements in Key Bodily Fluids]

Sodium (Na+)

Sodium (Na+) is the major cation of the extracellular fluid. It is responsible for one-half of the osmotic pressure gradient existing between the interior of cells and their surrounding environment. People eating a typical Western diet, which is very high in NaCl, routinely take in 130 to 160 mmol/day of sodium, but humans require only 1 to 2 mmol/day. Therefore, sodium deficiency is rare, and the main concern is adequate excretion of the excess in the urine. This excess sodium appears to be a major factor in hypertension (high blood pressure) in some people. Excretion of sodium is accomplished primarily by the kidneys. Sodium is freely filtered through the glomerular capillaries of the kidneys, and although much of the filtered sodium is reabsorbed in the proximal convoluted tubule, some remains in the filtrate and urine and are normally excreted. Sodium homeostasis is accomplished through the coordination of several hormones including antidiuretic hormone (ADH), aldosterone, and atrial natriuretic peptide (ANP). All three of these hormones affect sodium levels either directly or indirectly. The primary function of ANP is controlling blood volume by increasing sodium (and thus water) loss in the urine. Aldosterone, on the other hand, controls blood pressure and, like ANP, it accomplishes this by regulating sodium (and thus water) loss in the urine. However, ANP and aldosterone have opposite effects on sodium and water loss through urine. Aldosterone also has a direct effect on blood sodium levels, independent of its effect on blood pressure. ADH controls blood osmolarity through its effects on water conservation or loss but because the primary extracellular cation is sodium, ADH does affect the concentration of sodium indirectly.

Hyponatremia is a lower-than-normal concentration of sodium, usually associated with excess water accumulation in the body, which dilutes the sodium. A complete loss of sodium may be due to a decreased ion intake coupled with its continual excretion in the urine. An abnormal loss of sodium from the body can result from several conditions, including excessive sweating, vomiting, or diarrhea; the use of diuretics; excessive production of urine, which can occur in diabetes; and either metabolic acidosis or diabetic ketoacidosis.

A relative decrease in blood sodium can occur because of an imbalance of sodium in one of the body’s other fluid compartments, like interstitial fluid, or from a dilution of sodium due to water retention related to edema, congestive heart failure, or even very rapid ingestion of water. Hormonal disorders such as the syndrome of inappropriate antidiuretic hormone (SIADH) can also cause hyponatremia due to excess water retention and dilution of the body’s sodium content. At the cellular level, hyponatremia results in increased entry of water into red blood cells by osmosis, because the concentration of solutes within the cell exceeds the concentration of solutes in the now-diluted ECF. The excess water causes swelling of the cells, which decreases their oxygen-carrying efficiency and makes them potentially too large to fit through capillaries. Hyponatremia can also cause swelling of neurons in the brain and can result in brain damage or even death.

Hypernatremia is an abnormal increase of blood sodium. It can result from water loss from the blood, resulting in the hemoconcentration of all blood constituents. Hormonal imbalances involving hyposecretion of ADH in diabetes insipidus or hypersecretion of aldosterone, such as in an aldosteronoma, may also result in higher-than-normal sodium values.

Potassium (K+)

Potassium (K+) is the major intracellular cation. It helps establish the resting membrane potential in neurons and muscle fibers after membrane depolarization and action potentials. In contrast to sodium, potassium has minimal effect on osmotic pressure. The low potassium levels in blood and CSF are due to the sodium-potassium pumps in cell membranes, which maintain the normal potassium concentration gradients between the ICF and ECF. The recommendation for daily intake/consumption of potassium is 4700 mg. Potassium is actively and passively excreted, through the renal tubules, especially the distal convoluted tubule and collecting ducts. Potassium participates in the exchange with sodium in the renal tubules under the influence of aldosterone, which also relies on basolateral sodium-potassium pumps.

Potassium imbalances are the most dangerous type of electrolyte disorder in the body because potassium is primarily responsible for the resting membrane potential of cells. We keep blood plasma levels of potassium within a very narrow range of 3.6 to 5.2 mmol/L and do not tolerate more than slight deviations outside of this range due to its effect on the membrane potential. Hyperkalemia, or high potassium levels, can have different effects depending on the rate of change. When hyperkalemia happens rapidly, such as in a crush injury which releases massive amounts of intracellular potassium, it has the effect of depolarizing the membrane. As you may recall, the resting membrane potential is generated primarily by potassium leaking down its gradient from inside the cell to outside the cell. When potassium levels rapidly rise, the gradient is decreased causing the equilibrium potential of potassium to become less negative, and therefore, the resting membrane potential moves toward the threshold making it hyperexcitable. If the concentration of potassium rises enough the membrane may not be able to repolarize above the threshold causing muscle and nervous tissue to stop working. This can cause cardiac arrest. In states that use lethal injection, a large bolus (dose given quickly) of potassium is how prisoners given a “lethal injection” are executed. Alternatively, if potassium levels rise slowly, such as in renal failure or acidosis, muscle and nervous tissue become less excitable through the inactivation of voltage-gated sodium channels.

Hypokalemia can result from alkalosis, diarrhea, vomiting, dietary deficiency, heavy sweating, or excessive use of laxatives. In hypokalemia, the gradient between intracellular and extracellular potassium is elevated, which makes the equilibrium potential of potassium more negative. Therefore, resting membrane potentials become hyperpolarized and less excitable.

Calcium (Ca2+)

There is a great deal of calcium (Ca2+) in our bodies, and much of it is found in our skeletal system. where it lends hardness to the bone in the form of hydroxyapatite crystals. Not all the calcium found in bone is crystalized, and bone serves as a calcium reservoir to keep blood levels within a narrow range. Plasma calcium is an essential component of coagulation pathways. Intracellularly, calcium ions function as a second messenger and are essential for the exocytosis of neurotransmitters and other substances and are necessary for muscle contraction. Due to its role in cell signaling, calcium concentrations are kept extremely low within the cytosol and intracellular calcium typically remains sequestered in the smooth endoplasmic reticulum bound to a protein called calsequestrin. Another reason for such low intracellular calcium concentrations is the high intracellular phosphate levels. If calcium levels were not kept so low, calcium phosphate crystals would form. Calcium imbalances are not uncommon and blood levels are maintained between 8.6 and 10.3 mEq/L. However, not all the plasma calcium is active. Much of the calcium in the blood is bound to plasma proteins so that the free calcium is kept within a very narrow range of 4.5-5.1 mg/dL. As described in the chapter on the endocrine system (link to endocrine chapter: calcium homeostasis section), the maintenance of blood calcium is controlled primarily by parathyroid hormone and calcitonin. Vitamin D also plays a role, especially in intestinal absorption of calcium.

Hypercalcemia can be caused by acidosis, hyperparathyroidism, or hypothyroidism. Hypercalcemia inhibits sodium channels from opening and thus inhibits depolarization of excitable membranes of muscle and nervous tissue. Elevated calcium levels can, therefore, cause muscle weakness, suppress reflexes, and cause cardiac arrhythmias.

Hypocalcemia, on the other hand, can be caused by alkalosis, pregnancy, lactation, diarrhea, vitamin D deficiency, hyperthyroidism, or hypoparathyroidism. Hypocalcemia due to hypoparathyroidism is especially severe if the parathyroid glands are lost during thyroidectomy surgery which requires the replacement of the parathyroid hormone. Our bodies are more sensitive to low calcium levels than high calcium levels. Hypocalcemia increases sodium permeability of membranes and, therefore, causes depolarization and hyperexcitability of nervous and muscle tissue. This can result in seizures, muscle spasms, and tetany when levels become low enough. A characteristic of patients with hypocalcemia is a contraction of the muscles of the hands and feet called a carpopedal spasm.

Magnesium (Mg2+)

The majority of our magnesium (Mg2+) is found in bones (54%) and the intracellular fluid (45%). Magnesium is the second most abundant intracellular cation after potassium. Much of our intracellular magnesium is complexed with enzymes and functions as a cofactor that helps with the chemical reactions in many metabolic pathways and membrane transporters. Imbalances in magnesium can affect these metabolic pathways and affect membrane potential. Magnesium levels in the blood range from 1.5 to 2.0 mEq/L.

Like hypocalcemia, hypomagnesemia affects the resting membrane potential by making it more positive and thus causes hyperexcitability of muscle and nervous tissue resulting in muscle spasms or tetanus, hypertension from vasoconstriction and tachycardia, and arrhythmias. Hypomagnesemia can result from kidney disease or intestinal malabsorption, vomiting, or diarrhea.

Hypermagnesemia is rare and, like hypercalcemia, causes hyperpolarization of the resting membrane resulting in depression of the muscles and the nervous system. Hypermagnesemia is most often due to renal insufficiency and causes sedation, muscle weakness, hyporeflexia, hypotension due to loss of vasomotor tone, and bradycardia or cardiac arrest.

Phosphate (PO42-)

Phosphate is present in the body in three ionic forms: H2PO4−, HPO42−, and PO43−. The most common form is HPO42−. Bone and teeth contain 85% of the body’s phosphate as part of calcium phosphate salts. Phosphate is found in phospholipids, such as those that make up the cell membrane, and in ATP, nucleotides, and buffers. The ionic charge of phosphate is the reason why the phosphate head is the hydrophilic part of a phospholipid that faces the ECF and ICF.

Hypophosphatemia, or abnormally low phosphate blood levels, occurs with heavy use of antacids, during alcohol withdrawal, or during malnourishment. During phosphate depletion, the kidneys usually conserve phosphate, but during starvation, this conservation is impaired greatly. Hyperphosphatemia, or abnormally increased levels of phosphates in the blood, occurs if there is decreased renal function or in cases of acute lymphocytic leukemia. Additionally, because phosphate is a major constituent of the ICF, any significant destruction of cells can result in the dumping of phosphate into the ECF.

Chloride (Cl-)

Chloride (Cl-) is the predominant extracellular anion. Chloride is a principal contributor to the osmotic pressure gradient between the ICF and ECF and plays an essential role in maintaining proper hydration. Chloride functions to balance cations in the ECF, maintaining the electrical neutrality of this fluid. The paths of secretion and reabsorption of chloride ions in the renal system follow the paths of sodium ions. Regulation of chloride is passive and occurs secondarily to the regulation of sodium which chloride will follow.

Hypochloremia, or lower-than-normal blood chloride levels, can occur because of defective renal tubular absorption. Vomiting, diarrhea, excessive sweating, and acidosis can also lead to hypochloremia. Hyperchloremia, or higher-than-normal blood chloride levels, can occur due to dehydration, excessive intake of dietary salt (NaCl) or swallowing of seawater, aspirin intoxication, congestive heart failure, and the hereditary, chronic lung disease, or cystic fibrosis. In people who have cystic fibrosis, chloride levels in sweat are two to five times those of normal levels, and analysis of sweat is often used in the diagnosis of the disease.

26.4 Acid-Base Balance

Maintaining appropriate pH in the different compartments of the body is critical in the maintenance of homeostasis and health, which is the overall concept behind acid-base balance. For enzymes to fold and stay folded in the correct 3-dimensional shape, and thus function properly, the pH must be maintained within an ideal range. This pH range is different for different enzymes depending on the environment in which they work. For example, pepsin functions in the low pH of the stomach and have, therefore, evolved to function ideally in a very acidic environment. Carbonic anhydrase works only at a neutral pH because it catalyzes reactions in the blood. Because pH is such a critical parameter in the function of virtually every enzyme in our body, it should not be surprising that we have developed many different and redundant systems to maintain pH within narrow ranges in each body compartment. These systems include buffers, which function almost instantaneously at the site of acid or base production, the respiratory system, which functions rapidly within minutes to maintain blood pH, and our kidneys, which have an enormous capacity for removing acid from our bodies but work relatively slowly over hours to days.

Buffer systems

Buffer systems are extremely effective at preventing changes to pH and do so almost instantaneously. Because buffer systems function most effectively within a certain pH range, it should come as no surprise that the body has several different and overlapping buffer systems found in the pH of different body compartments. Buffer systems are made up of pairs of weak acids and their conjugate bases. To work as a buffer, a system must be able to compensate for the addition of acids or bases to maintain the pH of the system and solution. Weak acids can donate hydrogen ions (H+) if the pH increases and their conjugate bases will accept hydrogen ions if the pH decreases — only together can the pair maintain a steady pH. A general buffer system works like this:

weak acid ⇄ conjugate base + H+

Because we need both a weak acid and its conjugate base for a system to function as a buffer, buffers only work within a certain range. This is because outside of that range, either all the acid will be neutralized or all the base will be neutralized. For example, in our blood, about 95% of the carboxylic acid is ionized to form bicarbonate and hydrogen. Therefore, the 5% carboxylic acid can neutralize a base and the 95% bicarbonate can neutralize an acid. If we move into a much higher pH, all the carboxylic acids will be ionized and unable to donate any more hydrogen ions and there will no longer be an acid/base pair. On the other hand, if we lower the pH enough, all the bicarbonate will bind to hydrogen to form carboxylic acid, and no further hydrogen ions can be removed from the system, and there will no longer be an acid/base pair. Each buffer system works best within a pH range in which the acid/base pair is maintained.

The protein buffer system arises out of the inherent ability of all proteins and amino acids to function as buffers. Because each amino acid and protein has an amine group (or N-terminus) and a carboxylic acid group (or C-terminus) they have both the ability to accept or donate hydrogen ions. Hemoglobin is an especially important buffer due to its ability to bind H+ or CO2 during the transport of carbon dioxide to the lungs.

The phosphate buffer system works better in environments with lower pH than typically found in the blood, such as within cells and the kidney tubules. Phosphates in the body are found in two forms: sodium dihydrogen phosphate (Na2H2PO4−), which is a weak acid, and sodium monohydrogen phosphate (Na2HPO4 2-), which is a weak base. When Na2HPO4 2- comes into contact with a strong acid, such as HCl, the base picks up a second hydrogen ion to form the weak acid Na2H2PO4− and sodium chloride, NaCl. When Na2HPO4 2- (the weak acid) comes into contact with a strong base, such as sodium hydroxide (NaOH), the weak acid reverts to the weak base and produces water. Acids and bases are still present, but they hold onto the ions.

HCl     +   Na2HPO4   →   NaH2PO4   +   NaCl

(strong acid) + (weak base) → (weak acid) + (salt)

NaOH   +  NaH2PO4   → Na2HPO4       +  H2O

(strong base) + (weak acid) → (weak base) + (water)

The bicarbonate-carbonic acid buffer system (also, bicarbonate buffer system) works in a fashion similar to phosphate buffers. Levels of bicarbonate ions are regulated in the blood by sodium, as are the phosphate ions. When sodium bicarbonate (NaHCO3), comes into contact with a strong acid, such as HCl, carbonic acid (H2CO3), which is a weak acid, and NaCl are formed. When carbonic acid comes into contact with a strong base, such as NaOH, bicarbonate, and water are formed.

NaHCO3            +       HCl         →    H2CO3      + NaCl

(sodium bicarbonate) + (strong acid) → (weak acid) + (salt)

H2CO3     +      NaOH       →    HCO3-         +   H2O

(weak acid) + (strong base) → (bicarbonate) + (water)

As with the phosphate buffer, a weak acid or weak base captures the free ions, and a significant change in pH is prevented. Bicarbonate ions and carbonic acid are present in the blood in a 20:1 ratio if the blood pH is within the normal range. With 20 times more bicarbonate than carbonic acid, this capture system is most efficient at buffering changes that would make the blood more acidic. This is useful because most of the body’s metabolic wastes, such as lactic acid and ketones, are acids. Carbonic acid levels in the blood are controlled by the expiration of CO2 through the lungs. In red blood cells, carbonic anhydrase forces the dissociation of the acid, rendering the blood less acidic. Because of this acid dissociation, CO2 is exhaled (see equations above). The level of bicarbonate in the blood is controlled through the renal system, where bicarbonate ions in the renal filtrate are conserved and passed back into the blood. The bicarbonate buffer is the primary buffering system of the interstitial fluid surrounding the cells in tissues throughout the body.

Respiratory regulation of acid-base balance

The respiratory system contributes to the balance of acids and bases in the body by regulating the blood levels of carbonic acid (Figure 26.10). CO2 in the blood readily reacts with water to form carbonic acid, and the levels of CO2 and carbonic acid in the blood are in equilibrium. When the CO2 level in the blood rises (as it does when you hold your breath), the excess CO2 reacts with water to form additional carbonic acid, lowering blood pH. Increasing the rate and/or depth of respiration (which you might feel the “urge” to do after holding your breath) allows you to exhale more CO2. The loss of CO2 from the body reduces blood levels of carbonic acid and thereby adjusts the pH upward, toward normal levels. As you might have surmised, this process also works in the opposite direction. Excessive deep and rapid breathing (as in hyperventilation) rids the blood of CO2 and reduces the level of carbonic acid, making the blood too alkaline. This brief alkalosis can be remedied by rebreathing air that has been exhaled into a paper bag. Rebreathing exhaled air will rapidly bring blood pH down toward normal.

Figure 26.10: Respiratory Regulation of Blood pH

The chemical reactions that regulate CO2 and carbonic acid levels occur in the lungs when blood travels through the pulmonary capillaries. Minor adjustments in breathing are usually sufficient to adjust the pH of the blood by changing how much CO2 is exhaled. Doubling the respiratory rate for less than 1 minute, removing “extra” CO2, would increase the blood pH by 0.2. This situation is common if you are exercising strenuously over some time. To keep up the necessary energy production, you would produce excess CO2 (and lactic acid if exercising beyond your aerobic threshold). To balance the increased acid production, the respiration rate goes up to remove the CO2. This helps to keep you from developing acidosis. The body regulates the respiratory rate using chemoreceptors, which primarily use CO2 as a signal, and these peripheral blood sensors are found in the walls of the aorta and carotid arteries. These sensors signal the brain to provide immediate adjustments to the respiratory rate if CO2 levels rise or fall. Other sensors are found in the brain itself. Changes in the pH of CSF affect the respiratory center in the medulla oblongata, which can directly modulate breathing rate to bring the pH back into the normal range. Hypercapnia, or abnormally elevated blood levels of CO2, occurs in any situation that impairs respiratory functions, including pneumonia and congestive heart failure. Reduced breathing (hypoventilation) due to drugs such as morphine, barbiturates, or ethanol (or even just holding one’s breath) can also result in hypercapnia. Hypocapnia, or abnormally low blood levels of CO2, occurs with any cause of hyperventilation that drives off the CO2, such as salicylate toxicity, elevated room temperatures, fever, or a panic attack.

Renal Excretion of H+ and regulation of acid-base balance

The renal regulation of the body’s acid-base balance addresses the metabolic component of the buffering system. Whereas the respiratory system (together with breathing centers in the brain) controls the blood levels of carbonic acid by controlling the exhalation of CO2, the renal system controls the blood levels of bicarbonate. A decrease in blood bicarbonate can result from the inhibition of carbonic anhydrase by certain diuretics or from excessive bicarbonate loss due to diarrhea. Blood bicarbonate levels are also typically lower in people who have Addison’s disease (chronic adrenal insufficiency), in which aldosterone levels are reduced, and in people with renal damage, such as chronic nephritis. Finally, low bicarbonate blood levels can result from elevated levels of ketones (common in unmanaged diabetes mellitus), which bind bicarbonate in the glomerular filtrate and prevent its conservation.

Bicarbonate ions, HCO3-, found in the glomerular filtrate, are essential to the bicarbonate buffer system, yet the tubule cells are not permeable to bicarbonate ions. The steps involved in supplying bicarbonate ions to the system are seen in (Figure x.acidbase.renal) and are summarized below:

• Step 1: Sodium ions are reabsorbed from the filtrate in exchange for H+ by an antiport mechanism in the apical membranes of cells lining the renal tubule. H+ combines with bicarbonate in the filtrate to form CO2 which diffuses into the cell.
• Step 2: CO2 recombines with water to form carbonic acid which dissociates into bicarbonate and hydrogen. The bicarbonate is then transported into the blood in the peritubular capillaries and the H+ is transported back into the tubule to repeat the cycle and reclaim another bicarbonate.

Figure 26.11: Conservation of Bicarbonate in the Kidney (from OpenStax]

It is also possible that salts in the filtrate, such as sulfates, phosphates, or ammonia, will capture hydrogen ions as part of the renal buffer system. If this occurs, the hydrogen ions will not be available to combine with bicarbonate ions and produce CO2. In such cases, bicarbonate ions are not conserved from the filtrate to the blood, which will also contribute to a pH imbalance and acidosis.

The hydrogen ions also compete with potassium to exchange with sodium in the renal tubules. If more potassium is present than normal, potassium, rather than the hydrogen ions, will be exchanged, and increased potassium enters the filtrate. When this occurs, fewer hydrogen ions in the filtrate participate in the conversion of bicarbonate into CO2, and less bicarbonate is conserved. If there is less potassium, more hydrogen ions enter the filtrate to be exchanged with sodium and more bicarbonate is conserved.

Chloride ions are important in neutralizing positive ion charges in the body. If chloride is lost, the body uses bicarbonate ions in place of the lost chloride ions. Thus, lost chloride results in increased reabsorption of bicarbonate by the renal system.

Another important role in pH regulation by the kidneys is the excretion of hydrogen ions. This occurs in the distal convoluted tubule and the collecting duct and is stimulated in conditions of acidosis. The kidneys have a great capacity to concentrate hydrogen ions in the filtrate and will continue to secrete them until the limiting pH is reached. The limiting pH is the gradient of hydrogen ions against which the hydrogen pumps can no longer transport hydrogen ions. The limiting pH in the kidneys is around 4.5, which represents a thousand-fold difference between the hydrogen ion concentration in the blood versus the kidney tubules. Excretion of hydrogen ions in the kidneys is facilitated by the presence of buffers in the filtrate including sulfates, phosphates, and ammonia, which further increases the capacity of the kidneys to remove hydrogen ions.

Finally, the proximal tubule can generate “new” bicarbonate ions by metabolizing the amino acid glutamine. During glutamine metabolism, the proximal tubules produce two ammonia and two bicarbonate ions for each amino acid. The ammonia is transported into the tubule, where it buffers hydrogen ions, thus increasing the capacity to transport hydrogen ions into the filtrate. The bicarbonate ions are transported into the blood, where they can buffer hydrogen ions in the plasma.

The conservation and production of bicarbonate ions, together with the ability of the kidneys to excrete and concentrate hydrogen ions, represent the body’s most potent defense against changes in pH. Although the kidneys are extremely effective at regulating pH, they do not work quickly and are, therefore, not effective at controlling rapid shifts in pH.

Acid-base disorders

Normal arterial blood pH is restricted to a very narrow range of 7.35 to 7.45. A person who has a blood pH below 7.35 is considered to be in acidosis, and a continuous blood pH below 7.0 can be fatal. Acidosis has several symptoms, including headache and confusion, and the individual can become lethargic and easily fatigued (Figure 26.12). A person who has a blood pH above 7.45 is considered to be in alkalosis, and a pH above 7.8 is fatal. Some symptoms of alkalosis include cognitive impairment (which can progress to unconsciousness), tingling or numbness in the extremities, muscle twitching and spasm, and nausea and vomiting. Both acidosis and alkalosis can be caused by either metabolic or respiratory disorders.

As discussed earlier in this chapter, the concentration of carbonic acid in the blood is dependent on the level of CO2 in the body, and the amount of CO2 gas exhaled through the lungs. Thus, the respiratory contribution to acid-base balance is usually discussed in terms of CO2 (rather than carbonic acid). Remember that a molecule of carbonic acid is lost for every molecule of CO2 exhaled, and a molecule of carbonic acid is formed for every molecule of CO2 retained. The metabolic contribution to acid-base balance is usually discussed in terms of bicarbonate. To assess acid-base balance it is necessary to obtain an arterial blood gas (ABG) sample to get the data necessary to diagnose the condition.

Figure 26.12: Symptoms of Acidosis and Alkalosis

Respiratory Acidosis

Respiratory acidosis is caused by anything that inhibits respiration or interferes with gas exchange in the lungs. The result of inhibited or impaired respiration or impaired gas exchange is an accumulation of CO2 in the blood, which is converted to carbonic acid thus lowering the pH. Thus, the primary indication of respiratory acidosis is elevated blood CO2 levels in an ABG sample.

Things that can inhibit respiration include brainstem injuries, sleep apnea, and certain drugs such as opioids or paralytics. Respiration can be impaired by neuromuscular disorders such as amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). Some of the things that can impair gas exchange include disorders such as emphysema and pneumonia. Respiratory acidosis is treated by administration of bicarbonate and respiratory therapy when indicated.

Respiratory Alkalosis

Respiratory alkalosis is caused by excessive CO2 exchange between the blood and the atmosphere due to hyperventilation. Hyperventilation, or an increased rate and/or depth of breathing, can be caused by anxiety, fear, pain, low oxygen levels due to high altitude, or fever. Respiratory alkalosis could be diagnosed by low arterial CO2 levels and can be treated by using relaxation methods or by breathing into a paper bag to reclaim the exhaled CO2.

Metabolic Acidosis

Metabolic acidosis is caused by conditions that result in a decrease in blood bicarbonate levels. A common mnemonic used to remember some of the more common causes of metabolic acidosis is MUDD PILES. In the table below, substitute lactic acid for strenuous exercise to make the mnemonic work. Metabolic acidosis is diagnosed by low levels of bicarbonate in the blood. Metabolic acidosis is treated by the administration of bicarbonate and by finding the cause of the condition and treating it.

Table 26.1 Common Causes of Metabolic Acidosis and Blood Metabolites

Metabolic Alkalosis

Metabolic alkalosis is caused by conditions that result in elevated blood bicarbonate levels. This can be caused by vomiting or gastric suctioning resulting in the loss of stomach acid, or by ingestion of bicarbonate in the treatment of heartburn. It can also be caused by Cushing’s disease or by other conditions that result in hypokalemia such as the use of certain diuretics. Like metabolic acidosis, this condition is diagnosed by the presence of elevated bicarbonate levels in the blood and is corrected by treating the condition that caused it.

Compensation

Various compensatory mechanisms exist to maintain blood pH within a narrow range, including buffers, respiration, and renal mechanisms. Although compensatory mechanisms usually work very well, when one of these mechanisms is not working properly (like kidney failure or respiratory disease), they may become extremely limited. If the pH and bicarbonate to carbonic acid ratio change too drastically, the body may not be able to compensate, and as discussed earlier, extreme changes in pH can denature proteins. Extensive damage to proteins in this way can disrupt normal metabolic processes, severe tissue damage, and ultimately death.

Respiratory compensation for metabolic acidosis increases the respiratory rate to drive off CO2 and readjust the bicarbonate to carbonic acid ratio to the 20:1 level. This adjustment can occur within minutes. Respiratory compensation for metabolic alkalosis is not as adept as its compensation for acidosis. The typical response of the respiratory system to elevated pH is to increase the amount of CO2 in the blood by decreasing the respiratory rate to conserve CO2. There is a limit to the decrease in respiration, however, that the body can tolerate due to the need for oxygen. Hence, the respiratory route is less efficient at compensating for metabolic alkalosis than for acidosis.

Metabolic and renal compensation for respiratory diseases that can create acidosis revolves around the conservation and generation of bicarbonate ions. In cases of respiratory acidosis, the kidney increases the conservation and production of bicarbonate and secretion of H+ through the mechanisms discussed earlier. These processes increase the concentration of bicarbonate in the blood, reestablishing the proper relative concentrations of bicarbonate and carbonic acid. In cases of respiratory alkalosis, the kidneys decrease the production of bicarbonate and decrease the secretion of H+ into the tubular fluid.

Chapter Summary

References

• Some material taken from openstax chapter 26 fluid, electrolyte, and acid-base balance
• Call Out Box: Local Problems: Water Rights — Access to ʻAuwai
  • https://www.ksbe.edu/article/ola-i-ka-wai-protecting-hawaiis-freshwater-resources/
  • https://www.taylorfrancis.com/chapters/edit/10.4324/9780203796009-19/organizing-environmental-justice-bridges-taro-patches-amy-krings-michael-spencer-kelcie-jimenez
  • Organizing for Environmental Justice: From Bridges to Taro Patches — https://www.taylorfrancis.com/chapters/edit/10.4324/9780203796009-19/organizing-environmental-justice-bridges-taro-patches-amy-krings-michael-spencer-kelcie-jimenez
• Fluid Compartments
  • Openstax
  • 5’9 70 kg male vs “average” adult male: https://www.cdc.gov/nchs/fastats/body-measurements.htm
• Water balance
  • Insensible water loss — https://pubmed.ncbi.nlm.nih.gov/30212412/
  • Peritoneal fluid volume — https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584112/
  • Pleural fluid — https://www.mdpi.com/2571-841X/5/1/6/pdf
• Alkaline water:
  • https://www.medicalnewstoday.com/articles/313681#how-to-make-alkaline-water

Key Terms

antidiuretic hormone (ADH)

also known as vasopressin, a hormone that increases the volume of water reabsorbed from the collecting tubules of the kidney

dehydration

state of containing insufficient water in blood and other tissues

diuresis

excess production of urine

extracellular fluid (ECF)

fluid exterior to cells; includes the interstitial fluid, blood plasma, and fluids found in other reservoirs in the body

fluid compartment

fluid inside all cells of the body constitutes a compartment system that is largely segregated from other systems

hypercalcemia

abnormally increased blood levels of calcium

hypercapnia

abnormally elevated blood levels of CO2

hyperchloremia

higher-than-normal blood chloride levels

hyperkalemia

higher-than-normal blood potassium levels

hypermagnesemia

higher-than-normal blood magnesium levels

hypernatremia

abnormal increase in blood sodium levels

hyperphosphatemia

abnormally increased blood phosphate levels

hypocalcemia

abnormally low blood levels of calcium

hypocapnia

abnormally low blood levels of CO2

hypochloremia

lower-than-normal blood chloride levels

hypokalemia

abnormally decreased blood levels of potassium

hypomagnesemia

lower-than-normal blood magnesium levels

hyponatremia

lower-than-normal levels of sodium in the blood

hypophosphatemia

abnormally low blood phosphate levels

interstitial fluid (IF)

fluid in the small spaces between cells not contained within blood vessels

intracellular fluid (ICF)

fluid in the cytosol of cells

metabolic acidosis

condition wherein a deficiency of bicarbonate causes the blood to be overly acidic

metabolic alkalosis

condition wherein an excess of bicarbonate causes the blood to be overly alkaline

plasma osmolality

ratio of solutes to a volume of solvent in the plasma; plasma osmolality reflects a person’s state of hydration

respiratory acidosis

condition wherein an excess of carbonic acid or CO2 causes the blood to be overly acidic

respiratory alkalosis

condition wherein a deficiency of carbonic acid/CO2 levels causes the blood to be overly alkaline