breathing and acid base balance experiment

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26.4 Acid-Base Balance

Learning objectives.

By the end of this section, you will be able to:

• Identify the most powerful buffer system in the body
• Identify the most rapid buffer system in the body
• Describe the protein buffer systems.
• Explain the way in which the respiratory system affects blood pH
• Describe how the kidney affects acid-base balance

Proper physiological functioning depends on a very tight balance between the concentrations of acids and bases in the blood. Acid-balance balance is measured using the pH scale, as shown in Figure 26.4.1 . A variety of buffering systems permits blood and other bodily fluids to maintain a narrow pH range, even in the face of perturbations. A buffer is a chemical system that prevents a radical change in fluid pH by dampening the change in hydrogen ion concentrations in the case of excess acid or base. Most commonly, the substance that absorbs the ions is either a weak acid, which takes up hydroxyl ions, or a weak base, which takes up hydrogen ions.

Buffer Systems in the Body

The buffer systems in the human body are extremely efficient, and different systems work at different rates. It takes only seconds for the chemical buffers in the blood to make adjustments to pH. The respiratory tract can adjust the blood pH upward in minutes by exhaling CO 2 from the body. The renal system can also adjust blood pH through the excretion of hydrogen ions (H + ) and the conservation of bicarbonate, but this process takes hours to days to have an effect.

The buffer systems functioning in blood plasma include plasma proteins, phosphate, and bicarbonate and carbonic acid buffers. The kidneys help control acid-base balance by excreting hydrogen ions and generating bicarbonate that helps maintain blood plasma pH within a normal range. Protein buffer systems work predominantly inside cells.

Protein Buffers in Blood Plasma and Cells

Nearly all proteins can function as buffers. Proteins are made up of amino acids, which contain positively charged amino groups and negatively charged carboxyl groups. The charged regions of these molecules can bind hydrogen and hydroxyl ions, and thus function as buffers. Buffering by proteins accounts for two-thirds of the buffering power of the blood and most of the buffering within cells.

Hemoglobin as a Buffer

Hemoglobin is the principal protein inside of red blood cells and accounts for one-third of the mass of the cell. During the conversion of CO 2 into bicarbonate, hydrogen ions liberated in the reaction are buffered by hemoglobin, which is reduced by the dissociation of oxygen. This buffering helps maintain normal pH. The process is reversed in the pulmonary capillaries to re-form CO 2 , which then can diffuse into the air sacs to be exhaled into the atmosphere. This process is discussed in detail in the chapter on the respiratory system.

Phosphate Buffer

Phosphates are found in the blood in two forms: sodium dihydrogen phosphate (Na 2 H 2 PO 4 − ), which is a weak acid, and sodium monohydrogen phosphate (Na 2 HPO4 2- ), which is a weak base. When Na 2 HPO4 2-  comes into contact with a strong acid, such as HCl, the base picks up a second hydrogen ion to form the weak acid Na 2 H 2 PO 4 − and sodium chloride, NaCl. When Na 2 HPO4 2− (the weak acid) comes into contact with a strong base, such as sodium hydroxide (NaOH), the weak acid reverts back to the weak base and produces water. Acids and bases are still present, but they hold onto the ions.

Bicarbonate-Carbonic Acid Buffer

The bicarbonate-carbonic acid buffer works in a fashion similar to phosphate buffers. The bicarbonate is regulated in the blood by sodium, as are the phosphate ions. When sodium bicarbonate (NaHCO 3 ), comes into contact with a strong acid, such as HCl, carbonic acid (H 2 CO 3 ), 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.

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 CO 2 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, CO 2 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. However, the bicarbonate buffer is the primary buffering system of the IF surrounding the cells in tissues throughout the body.

CO 2 + H 2 O ↔ H 2 CO 3 ↔ H + + HCO 3 –

Respiratory Regulation of Acid-Base Balance

The chemical reactions that regulate the levels of CO 2 and carbonic acid occur in the lungs when blood travels through the lung’s pulmonary capillaries. Minor adjustments in breathing are usually sufficient to adjust the pH of the blood by changing how much CO 2 is exhaled. In fact, doubling the respiratory rate for less than 1 minute, removing “extra” CO 2 , would increase the blood pH by 0.2. This situation is common if you are exercising strenuously over a period of time. To keep up the necessary energy production, you would produce excess CO 2 (and lactic acid if exercising beyond your aerobic threshold). In order to balance the increased acid production, the respiration rate goes up to remove the CO 2 . This helps to keep you from developing acidosis.

The body regulates the respiratory rate by the use of chemoreceptors, which primarily use CO 2 as a signal. 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 CO 2 levels rise or fall. Yet 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 CO 2 , 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 CO 2 , occurs with any cause of hyperventilation that drives off the CO 2 , such as salicylate toxicity, elevated room temperatures, fever, or hysteria.

Renal 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 CO 2 , the renal system controls the blood levels of bicarbonate. A decrease of 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 who have 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 filtrate and prevent its conservation.

Bicarbonate ions, HCO 3 – , found in the filtrate, are essential to the bicarbonate buffer system, yet the cells of the tubule are not permeable to bicarbonate ions. The steps involved in supplying bicarbonate ions to the system are seen in Figure 26.4.3 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.
• Step 2: The cells produce bicarbonate ions that can be shunted to peritubular capillaries.
• Step 3: When CO 2 is available, the reaction is driven to the formation of carbonic acid, which dissociates to form a bicarbonate ion and a hydrogen ion.
• Step 4: The bicarbonate ion passes into the peritubular capillaries and returns to the blood. The hydrogen ion is secreted into the filtrate, where it can become part of new water molecules and be reabsorbed as such, or removed in the urine.

It is also possible that salts in the filtrate, such as sulfates, phosphates, or ammonia, will capture hydrogen ions. If this occurs, the hydrogen ions will not be available to combine with bicarbonate ions and produce CO 2 . 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 CO 2 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 an increased reabsorption of bicarbonate by the renal system.

Disorders of the… Fluid Balance: Acid-Base Balance: Ketoacidosis

Diabetic acidosis, or ketoacidosis, occurs most frequently in people with poorly controlled diabetes mellitus. When certain tissues in the body cannot get adequate amounts of glucose, they depend on the breakdown of fatty acids for energy. When acetyl groups break off the fatty acid chains, the acetyl groups then non-enzymatically combine to form ketone bodies, acetoacetic acid, beta-hydroxybutyric acid, and acetone, all of which increase the acidity of the blood. In this condition, the brain isn’t supplied with enough of its fuel—glucose—to produce all of the ATP it requires to function.

Ketoacidosis can be severe and, if not detected and treated properly, can lead to diabetic coma, which can be fatal. A common early symptom of ketoacidosis is deep, rapid breathing as the body attempts to drive off CO 2 and compensate for the acidosis. Another common symptom is fruity-smelling breath, due to the exhalation of acetone. Other symptoms include dry skin and mouth, a flushed face, nausea, vomiting, and stomach pain. Treatment for diabetic coma is ingestion or injection of sugar; its prevention is the proper daily administration of insulin.

A person who is diabetic and uses insulin can initiate ketoacidosis if a dose of insulin is missed. Among people with type 2 diabetes, those of Hispanic and African-American descent are more likely to go into ketoacidosis than those of other ethnic backgrounds, although the reason for this is unknown.

Chapter Review

A variety of buffering systems exist in the body that helps maintain the pH of the blood and other fluids within a narrow range—between pH 7.35 and 7.45. A buffer is a substance that prevents a radical change in fluid pH by absorbing excess hydrogen or hydroxyl ions. Most commonly, the substance that absorbs the ion is either a weak acid, which takes up a hydroxyl ion (OH – ), or a weak base, which takes up a hydrogen ion (H + ). Several substances serve as buffers in the body, including cell and plasma proteins, hemoglobin, phosphates, bicarbonate ions, and carbonic acid. The bicarbonate buffer is the primary buffering system of the IF surrounding the cells in tissues throughout the body. The respiratory and renal systems also play major roles in acid-base homeostasis by removing CO 2 and hydrogen ions, respectively, from the body.

Review Questions

Critical thinking questions.

1. Describe the conservation of bicarbonate ions in the renal system.

2. Describe the control of blood carbonic acid levels through the respiratory system.

Answers for Critical Thinking Questions

• Bicarbonate ions are freely filtered through the glomerulus. They cannot pass freely into the renal tubular cells and must be converted into CO 2 in the filtrate, which can pass through the cell membrane. Sodium ions are reabsorbed at the membrane, and hydrogen ions are expelled into the filtrate. The hydrogen ions combine with bicarbonate, forming carbonic acid, which dissociates into CO 2 gas and water. The gas diffuses into the renal cells where carbonic anhydrase catalyzes its conversion back into a bicarbonate ion, which enters the blood.
• Carbonic acid blood levels are controlled through the respiratory system by the expulsion of CO 2 from the lungs. The formula for the production of bicarbonate ions is reversible if the concentration of CO 2 decreases. As this happens in the lungs, carbonic acid is converted into a gas, and the concentration of the acid decreases. The rate of respiration determines the amount of CO 2 exhaled. If the rate increases, less acid is in the blood; if the rate decreases, the blood can become more acidic.

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Anatomy & Physiology Copyright © 2019 by Lindsay M. Biga, Staci Bronson, Sierra Dawson, Amy Harwell, Robin Hopkins, Joel Kaufmann, Mike LeMaster, Philip Matern, Katie Morrison-Graham, Kristen Oja, Devon Quick, Jon Runyeon, OSU OERU, and OpenStax is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License , except where otherwise noted.

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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

StatPearls [Internet].

Physiology, acid base balance.

Erin Hopkins ; Terrence Sanvictores ; Sandeep Sharma .

Affiliations

Last Update: September 12, 2022 .

• Introduction

To maintain homeostasis, the human body employs many physiological adaptations. One of these is maintaining an acid-base balance. In the absence of pathological states, the pH of the human body ranges between 7.35 to 7.45, with the average at 7.40. Why this number? Why not a neutral number of 7.0 instead of a slightly alkaline 7.40? A pH at this level is ideal for many biological processes, 1 of the most important being blood oxygenation. Also, many of the intermediates of biochemical reactions in the body become ionized at a neutral pH, which makes the utilization of these intermediates more difficult.

A pH below 7.35 is an acidemia, and a pH above 7.45 is an alkalemia. Due to the importance of sustaining a pH level in the needed narrow range, the human body contains compensatory mechanisms. This discussion intends to impart a basic understanding of acid-base balance in the body while providing a systematic way to approach patients who present with conditions causing alterations in pH.

The human body experiences 4 main types of acid-based disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. If 1 of these conditions occurs, the human body should induce a counterbalance in the form of an opposite condition. For example, if a person is experiencing metabolic acidemia, their body attempts to induce respiratory alkalosis to compensate. It is rare for the compensation to make the pH completely normal at 7.4. When using the term acidemia or alkalemia, 1 denotes that overall, the pH is acidic or alkalotic, respectively. While not necessary, it can be useful to employ this terminology to distinguish between individual processes and the overall pH status of the patient since multiple imbalances can happen simultaneously. [1] [2]

• Cellular Level

A basic comprehension of respiration at the cellular level is important in understanding acid-base equilibrium in the human body. Aerobic cellular respiration is necessary for human life; humans are obligate aerobes. While individual cells can perform anaerobic respiration, in order to sustain life, oxygen must be present. One of the byproducts of aerobic cellular respiration is carbon dioxide. The simplified chemical equation denoting aerobic cellular respiration is:

• C 6 H 12 O 6 (glucose) + 6O 2 --> 6CO 2 + 6H 2 0 + energy (38 ATP molecules and heat)

The first stage of cellular respiration is glycolysis, which takes a 6-carbon glucose and breaks it down into 2 pyruvate molecules which contain 3 carbons each. Glycolysis uses 2 ATP and creates 4 ATP, generating 2 net ATP. This process does not need oxygen to occur. Since patients are often deficient, it is worth noting that magnesium is a cofactor for 2 reactions in glycolysis.

Eventually, the pyruvate molecules are oxidized and enter into the TCA Cycle. The TCA cycle generates NADH from NAD+, FADH 2 from FAD, and 2 ATP molecules. It is an aerobic process and does demand oxygen. Pyruvate is brought into the mitochondria and forms acetyl-CoA with the loss of carbon dioxide. This excess carbon dioxide is then exhaled during the process of expiration.

The last step in aerobic cellular respiration is the electron transport chain (ETC). The ETC produces the majority of the ATP created in cellular respiration, with 34 ATP molecules being created. For the ETC reaction to occur, oxygen is needed. If there is not enough oxygen present, the products of glycolysis proceed to a reaction called fermentation to produce ATP. The byproduct of fermentation is lactic acid. During glycolysis and the TCA cycle, NAD+ is reduced to NADH, and FAD is reduced to FADH 2 . A gain of electrons characterizes reduction. This is what drives the ETC. For every single glucose molecule, 10 NAD+ molecules are converted to NADH molecules, which produce 3 ATP molecules a piece in the ETC.

This process of aerobic cellular respiration characterizes why humans need oxygen. Anaerobic respiration allows the body to produce some ATP when there is insufficient oxygen; however, the process only generates 2 instead of the 38 ATP produced with aerobic respiration. The 2 ATP molecules per reaction are not enough to sustain life. 

As noted above, carbon dioxide is produced as a byproduct of the TCA cycle. This carbon dioxide is instrumental to acid-base balance in the body which is demonstrated by the following reaction:

• CO 2 + H 2 0 <-> H 2 C0 3 <-> HCO 3 - + H+

The carbon dioxide formed during cellular respiration combines with water to create carbonic acid. Carbonic acid then dissociates into bicarbonate and a hydrogen ion. This reaction is 1 of the many buffer systems in the human body; it resists dramatic changes in pH to allow a person to remain within the narrow physiological pH range. This buffer system is in equilibrium; that is, all reaction components exist throughout the body and are shifted to the side of the equation appropriate for the environment. This reaction can and does occur without an enzyme; however, carbonic anhydrase is an enzyme that assists with this process. It catalyzes the first reaction above to form carbonic acid, which can then freely dissociate into bicarbonate and a hydrogen ion. Carbonic anhydrase is in red blood cells, renal tubules, gastric mucosa, and pancreatic cells.

Other buffer systems in the human body include the phosphate buffer system, proteins, and hemoglobin. All of these contain bases that accept hydrogen ions, which keep the pH from plummeting. The phosphate buffer system, while present globally, is important for the regulation of urine pH. Proteins assist with intracellular pH regulation. Red blood cells use the reaction above to help hemoglobin buffer; carbon dioxide can diffuse across red blood cells and combine with water. This alone would cause an increase in hydrogen ions; however, hemoglobin can bind hydrogen ions. Hemoglobin also can bind carbon dioxide without this reaction. This depends on the amount of oxygen that is bound to hemoglobin. This is called the Haldane effect and the Bohr effect. When hemoglobin is saturated with oxygen, it has a lower affinity for CO 2 and hydrogen ions and is able to release it. [3] [4]

• Organ Systems Involved

Every organ system of the human body relies on pH balance; however, the renal system and the pulmonary system are the 2 main modulators. The pulmonary system adjusts pH using carbon dioxide; upon expiration, carbon dioxide is projected into the environment. Due to carbon dioxide forming carbonic acid in the body when combined with water, the amount of carbon dioxide expired can cause pH to increase or decrease. When the respiratory system compensates for metabolic pH disturbances, the effect occurs in minutes to hours.

The renal system affects pH by reabsorbing bicarbonate and excreting fixed acids. Whether due to pathology or necessary compensation, the kidney excretes or reabsorbs these substances, which affect pH. The nephron is the functional unit of the kidney. Blood vessels called glomeruli transport substances found in the blood to the renal tubules so that some can be filtered out while others are reabsorbed into the blood and recycled. This is true for hydrogen ions and bicarbonate. If bicarbonate is reabsorbed and/or acid is secreted into the urine, the pH becomes more alkaline (increases). When bicarbonate is not reabsorbed, or acid is not excreted into the urine, pH becomes more acidic (decreases). The metabolic compensation from the renal system takes longer to occur: days rather than minutes or hours.

The physiological pH of the human body is essential for many processes necessary to life, including oxygen delivery to tissues, correct protein structure, and innumerable biochemical reactions that rely on the normal pH to be in equilibrium and complete.

Oxygen Delivery to Tissues

The oxygen dissociation curve is a graph depicting the relationship between the partial pressure of oxygen and the saturation of hemoglobin. This curve relates to the ability of hemoglobin to deliver oxygen to tissues. If the curve is shifted to the left, there is a decreased p50, meaning that the amount of oxygen needed to saturate hemoglobin 50% is lessened and an increased affinity of hemoglobin for oxygen. A pH in the alkalotic range induces this left shift. When there is a decrease in pH, the curve is shifted to the right, denoting a decreased affinity of hemoglobin for oxygen.

Protein Structure

It would be hard to overstate the importance of proteins in the human body. They comprise ion channels, carry necessary lipophilic substances throughout our mostly lipophobic body, and participate in innumerable biological processes. For proteins to complete necessary functions, they must be in the proper configuration. The charges on proteins are what allow their proper shape to exist. When pH is altered outside of the physiological range, these charges are altered. The proteins are denatured, leading to detrimental changes in architecture that cause a loss of proper function.

Biochemical Processes

Throughout the human body, many chemical reactions are in equilibrium. One of the most important was previously mentioned with the equation:

• H 2 0 + CO 2 <-> H 2 CO 3 <-> H+ + HCO 3 -

The Le Chatelier Principle states that when the variables of concentration, pressure, or temperature change, a system in equilibrium reacts accordingly to restore a new steady state. For the reaction above, this states that if more hydrogen ions are produced, the equation shifts to the left so that more reactants are formed, and the system can remain in equilibrium. This is how compensatory pH mechanisms work; if there is a metabolic acidosis present, the kidneys are not excreting enough hydrogen ions and/or not reabsorbing enough bicarbonate. The respiratory system reacts by increasing minute ventilation (often by increasing respiratory rate) and expiring more CO 2 to restore equilibrium. [5]

• Related Testing

Arterial blood gas (ABG) sampling is a test often performed in an inpatient setting to assess the acid-base status of a patient. A needle is used to draw blood from an artery, often the radial, and the blood is analyzed to determine parameters such as the pH, pC0 2 , pO 2 , HCO 3 , oxygen saturation, and more. This allows the physician to understand the status of the patient better. ABGs are especially important for the critically ill. They are the main tool utilized in adjusting to the needs of a patient on a ventilator. The following are the most important normal values on an ABG:

• pH = 7.35 to 7.45
• pCO 2 = 35 to 45 mmHg
• pO 2 = 75 to 100 mmHg
• HCO 3 - = 22 to 26 mEq/L
• O 2 Sat = greater than 95%

The ability to quickly and efficiently read an ABG, especially in reference to inpatient medicine, is paramount to quality patient care.

• Look at the pH
• Decide whether it is acidotic, alkalotic, or within the physiological range
• PaCO 2 level determines respiratory contribution; a high level means the respiratory system lowers the pH and vice versa.
• HCO 3 - level denotes metabolic/kidney effect. An elevated HCO 3 - is raising the pH and vice versa.
• If the pH is acidotic, look for the number corresponding to a lower pH. If it is a respiratory acidosis, the CO 2 should be high. If the patient is compensating metabolically, the HCO 3 - should also be high. Metabolic acidosis is depicted with an HCO 3 - that is low.
• If the pH is alkalotic, again, determine which value is causing this. A respiratory alkalosis means the CO 2 is low; a metabolic alkalosis should lend an HCO 3 - that is high. Compensation with either system is reflected oppositely; for respiratory alkalosis, the metabolic response should be a low HCO 3 - and for metabolic alkalosis, the respiratory response should be a high CO 2 .
• If the pH level is in the physiological range but the PaCO 2 and/or bicarb are not within normal limits, there is likely a mixed disorder. Also, compensation does not always occur; this is when clinical information becomes paramount.
• Sometimes it is difficult to ascertain whether a patient has a mixed disorder. This is discussed later.

Other tests that are important to perform when analyzing the acid-base status of a patient include those that measure electrolyte levels and renal function. This helps the clinician gather information that can be used to determine the exact mechanism of the acid-base imbalance and the factors contributing to the disorders. [6] [3]

• Pathophysiology

Increased Anion Gap Metabolic Acidosis

A primary metabolic acidosis, that is 1, which is the primary acid-base disorder, has many causes. These are separated into those that cause a high anion gap and those that do not. The plasma anion gap is a way to help clinicians determine the cause of metabolic acidosis. When there is a metabolic acidosis present, certain ions in the blood are measured that help determine the etiology of an acidemia. The anion gap increases whenever bicarbonate is lost due to combining with a hydrogen ion previously attached to a conjugate base. When bicarbonate combines with a hydrogen ion, the result is carbonic acid (H 2 CO 3 ). The conjugate base can be any negatively charged ion that isn’t a bicarbonate or a chloride. 

The formula for the anion gap is:

• [Na]-([Cl]+[HCO 3 ])

Humans are electrically neutral, but all cations and anions are not being measured. The normal anion gap is equal to 8 +/- 4. Most of this number is due to albumin; this anion is not accounted for in the formula, so the gap is not closer to zero. Albumin is normally 4 mg/dL. Because of the large effect of albumin on anion gap, if a patient’s albumin level is abnormal, their expected anion gap is inaccurate. This can be corrected using simple math. The normal anion gap and albumin level differ by a factor of 3 (normal anion gap of 12, normal albumin of  4 mg/dL). If a patient has an anion gap of 24, there are 12 units of the conjugate base present that normally would not be due to the combination of hydrogen ions with bicarbonate. If this same patient has an albumin level of 3mg/dL, their expected anion gap should actually be about 9. This means that rather than 12 units of the conjugate base present, there are really 15 units.

A more complex method of analyzing ion contribution to pH alterations is the strong ion difference/strong ion gap. This method emphasizes the effect of other ions on acid-base balance and is useful for learning about acid-base balance. However, this approach is more burdensome than the standard anion gap and involves more calculations. Many, therefore, believe that its use in clinical practice is limited.

The mnemonic MUDPILES has classically been used to teach students the causes of high anion gap metabolic acidosis. MUDPILES stands for methanol, uremia, diabetic ketoacidosis, paraldehyde, infection, lactic acidosis, ethylene glycol, and salicylates. A new mnemonic, GOLDMARK, has been suggested to be an improvement. GOLDMARK is an anagram for glycols (ethylene and propylene), oxoproline, lactate, methanol, aspirin, renal failure, and ketones. If a patient has an anion gap over 12, these mnemonics are helpful to remember the possible causes of the disorder. [7] [8]

Narrow Anion Gap Metabolic Acidosis

If the acidosis involves a normal anion gap, there is a loss of bicarbonate rather than an increased amount of hydrogen ions, with a concomitant increase in chloride ions. To keep a physiological neutral state, chloride ions migrate out of the cells and into the extracellular space. This causes the patient’s serum chloride to increase and keeps the anion gap at a normal level. This means a metabolic acidosis without an abnormal anion gap is also a hyperchloremic metabolic acidosis. A metabolic acidosis without an increased anion gap results from many processes, including severe diarrhea, type I renal tubular acidosis (RTA), long-term use of carbonic anhydrase inhibitors, and suctioning of gastric contents. When a patient has a narrow ion gap hyperchloremic acidosis, the provider can calculate the urine anion gap (UAG) to help determine the etiology. 

The following is the equation for the urine anion gap where Na is sodium, K is potassium, and Cl is chloride:

• (Na + K) – Cl

The renal system attempts to ameliorate the effects of pathological metabolic acidosis by excreting ammonium (NH4+) into the urine. A UAG between 20 to 90 mEq/L denotes low or normal NH4+ secretion. One between -20 mEq/L and -50 mEq/L suggests the main cause of the metabolic acidosis is prolonged severe diarrhea.

Another important formula to use with metabolic acidosis is the Winter formula. This equation provides the clinician with the expected PCO2 value. This is important because there could be another acid-base disorder present. 

The Winter formula is:

• Expected PCO 2 = (1.5 X HCO 3 ) + 8 +/- 2

If the PCO 2 value is within range of the expected PCO 2 , there is no mixed disorder, just respiratory compensation. When the value is lower or higher than expected, there is a mixed disorder; lower would mean respiratory alkalosis and higher respiratory acidosis. A shortcut for the Winter formula is that the last 2 digits of the pH +/- 2 are about equal to the expected PCO 2 . [9] [10]

Respiratory Acidosis

During exhalation, carbon dioxide produced by cellular respiration is projected into the environment. In the human body, carbon dioxide combines with water via carbonic anhydrase and forms carbonic acid, which dissociates into a hydrogen ion and bicarbonate. This is why a reduced respiratory rate leads to a decreased pH; the more carbon dioxide is exhaled, the less carbon dioxide is present for this reaction. 

Respiratory acidosis, as a primary disorder, is often caused by hypoventilation. This can be due to multiple causes, including chronic obstructive pulmonary disease, opiate abuse/overdose, severe obesity, and brain injury. When respiratory acidosis occurs, the metabolic response should increase the amount of bicarbonate via the renal system. This does not always occur, and renal pathology can easily hinder the appropriate physiological response, leading to increased danger for the patient.

Metabolic Alkalosis

Metabolic alkalosis can also be divided into 2 main categories that help ascertain the cause: chloride-responsive vs. non-chloride-responsive. In non-chloride-responsive metabolic alkalosis, the urine chloride is < 20 mEq/L. Some causes include vomiting, hypovolemia, and diuretic use. 

Respiratory Alkalosis

Any pathology that leads to the increased expiration of carbon dioxide can result in respiratory alkalosis. When excess CO 2 expires, the pH of the human body is increased due to less carbonic acid being created. Physiologically, the appropriate compensation is a decreased amount of bicarbonate being created by the renal system. Some causes of respiratory alkalosis include panic attacks with hyperventilation, pulmonary embolism, pneumonia, and salicylate intoxication. [11]

• Clinical Significance

Acid-base balance in the human body is 1 of the most paramount physiological processes. The clinical significance of acid-base balance is 1, which is hard to deny. Some of the most common admissions to hospitals are due to diseases that can dangerously affect the acid-base balance. This is why it is important for clinicians to understand the basic principles which govern this portion of human homeostasis.

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Disclosure: Erin Hopkins declares no relevant financial relationships with ineligible companies.

Disclosure: Terrence Sanvictores declares no relevant financial relationships with ineligible companies.

Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Hopkins E, Sanvictores T, Sharma S. Physiology, Acid Base Balance. [Updated 2022 Sep 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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• Incidence of metabolic alkalemia in hospitalized patients. [Crit Care Med. 1980] Incidence of metabolic alkalemia in hospitalized patients. Hodgkin JE, Soeprono FF, Chan DM. Crit Care Med. 1980 Dec; 8(12):725-8.
• Perioperative metabolic alkalemia is more frequent than metabolic acidemia in major elective abdominal surgery. [J Clin Monit Comput. 2011] Perioperative metabolic alkalemia is more frequent than metabolic acidemia in major elective abdominal surgery. Boaz M, Iskhakov A, Tsivian A, Shimonov M, Berkenstadt H, Izakson A, Szmuk P, Evron S, Muggia M, Ezri T. J Clin Monit Comput. 2011 Aug; 25(4):223-30. Epub 2011 Sep 23.
• Review Renal aspects of metabolic acid-base disorders in neonates. [Pediatr Nephrol. 2020] Review Renal aspects of metabolic acid-base disorders in neonates. Iacobelli S, Guignard JP. Pediatr Nephrol. 2020 Feb; 35(2):221-228. Epub 2018 Nov 19.
• Review Simple acid-base disorders. [Vet Clin North Am Small Anim P...] Review Simple acid-base disorders. Robertson SA. Vet Clin North Am Small Anim Pract. 1989 Mar; 19(2):289-306.

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Laboratory Report

Acid-Base Balance

current date

Predictions

Materials and methods.

• Explain why HCO 3 – levels can be calculated from pH and pCO 2 levels.
• In this experiment, HCO 3 – concentrations are calculated using pH and pCO 2 concentrations. Refer to the following chemical reaction to describe how changes in CO 2 and H + concentrations affect HCO 3 – concentration. CO 2 + H 2 O ⇌ H 2 CO 3 ⇌ H + + HCO 3 –

• Patient with respiratory acidosis
• Patient with respiratory alkalosis
• Patient with metabolic acidosis
• Patient with metabolic alkalosis
• Is compensation occurring in the patient with respiratory acidosis? State which system (respiratory or renal) is involved in compensation and what compound is being removed or added to achieve compensation. Describe how this substance is being removed or added and how removing or adding this compound returns pH toward normal.
• Is compensation occurring in the patient with respiratory alkalosis? State which system (respiratory or renal) is involved in compensation and what compound is being removed or added to achieve compensation. Describe how this substance is being removed or added and how removing or adding this compound returns pH toward normal.
• Is compensation occurring in the patient with metabolic acidosis? State which system (respiratory or renal) is involved in compensation and what compound is being removed or added to achieve compensation. Describe how this substance is being removed or added and how removing or adding this compound returns pH toward normal.
• Is compensation occurring in the patient with metabolic alkalosis? State which system (respiratory or renal) is involved in compensation and what compound is being removed or added to achieve compensation. Describe how this substance is being removed or added and how removing or adding this compound returns pH toward normal.
• Restate your predictions that were correct and give the data from your experiment that supports them. Restate your predictions that were not correct and correct them, giving the data from your experiment that supports the corrections.

Application

• Patients with COPD (Chronic Obstructive Pulmonary Disease) may develop respiratory acidosis. Explain how COPD causes respiratory acidosis and why breathing rate is elevated in COPD patients with respiratory acidosis.
• You can only hold your breath for a limited period of time before you involuntarily begin breathing again. Describe feedback mechanisms that result in involuntary breathing.
• Anxiety can cause hyperventilation. Explain how anxiety can cause hyperventilation and how hyperventilation causes respiratory alkalosis.
• Patients with uncontrolled diabetes can develop metabolic acidosis. Explain how uncontrolled diabetes causes metabolic acidosis.

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Respiratory Rate

pCO 2 concentration

HCO 3 - concentration

Acid-Base Disorder

Compensation

• DNA Replication
• Active Transport
• Cellular Receptors
• Endocytosis and Exocytosis
• Enzyme Inhibition
• Enzyme Kinetics
• Protein Structure
• Transcription of DNA
• Translation of DNA
• Anaerobic Respiration
• Electron Transport Chain
• Gluconeogenesis
• Calcium Regulation
• External Balance of Potassium
• Internal Balance of Potassium
• Sodium Regulation
• Cell Membrane
• Endoplasmic Reticulum
• Golgi Apparatus
• Mitochondria
• Blood Vessels
• Cellular Adaptations
• Epithelial Cells
• Muscle Histology
• Structure of Glands
• Control of Stroke Volume
• Control of Heart Rate
• Cardiac Cycle
• Cardiac Pacemaker Cells
• Conduction System
• Contraction of Cardiac Muscle
• Ventricular Action Potentials
• Blood Flow in Vessels
• Control of Blood Pressure
• Capillary Exchange
• Flow In Peripheral Circulation
• Venous Return
• Cardiac Muscle
• Hepatic Circulation
• Skeletal Muscle
• Airway Resistance
• Lung Volumes
• Mechanics of Breathing
• Gas Exchange
• Oxygen Transport in The Blood
• Transport of Carbon Dioxide in the Blood
• Ventilation-Perfusion Matching
• Chemoreceptors
• Cough Reflex
• Neural Control of Ventilation

Respiratory Regulation of Acid-Base Balance

• Responses of The Respiratory System to Stress
• Regulation of Saliva
• Secretion of Saliva
• Gastric Acid Production
• Gastric Mucus Production
• Digestion and Absorption
• Histology and Cellular Function of the Small Intestine
• Absorption in the Large Intestine
• Large Intestinal Motility
• Bilirubin Metabolism
• Carbohydrate Metabolism in the Liver
• Lipid Metabolism in the Liver
• Protein and Ammonia Metabolism in the Liver
• Storage Functions of the Liver
• Bile Production
• Function of The Spleen
• Exocrine Pancreas
• Somatostatin
• Proximal Convoluted Tubule
• Loop of Henle
• Distal Convoluted Tubule and Collecting Duct
• Storage Phase of Micturition
• Voiding Phase of Micturition
• Antidiuretic Hormone
• Renin-Angiotensin-Aldosterone System
• Urinary Regulation of Acid-Base Balance
• Water Filtration and Reabsorption
• Development of the Reproductive System
• Gametogenesis
• Gonadotropins and the Hypothalamic Pituitary Axis
• Menstrual Cycle
• Placental Development
• Fetal Circulation
• Maternal Adaptations in Pregnancy
• Cells of the Nervous System
• Central Nervous System
• Cerebrospinal Fluid
• Neurotransmitters
• Peripheral Nervous System
• Action Potential
• Excitatory and Inhibitory Synaptic Signalling
• Resting Membrane Potential
• Synaptic Plasticity
• Synaptic Transmission
• Ascending Tracts
• Auditory Pathway
• Consciousness and Sleep
• Modalities of Sensation
• Pain Pathways
• Sensory Acuity
• Visual Pathway
• Descending Tracts
• Lower Motor Neurones
• Muscle Stretch Reflex
• Upper Motor Neurones
• Aqueous Humour
• Ocular Accommodation
• Thyroid Gland
• Parathyroid Glands
• Adrenal Medulla
• Zona Glomerulosa
• Zona Fasciculata
• Zona Reticularis
• Endocrine Pancreas
• The Hypothalamus
• Anterior Pituitary
• Posterior Pituitary
• White Blood Cells – Summary
• Barriers to Infection
• Infection Recognition Molecules
• Phagocytosis
• The Complement System
• Antigen Processing and Presentation
• Primary and Secondary Immune Responses
• T Cell Memory
• Acute Inflammation
• Autoimmunity
• Chronic Inflammation
• Hypersensitivity Reactions
• Immunodeficiency
• Types of Immunity
• Antibiotics
• Viral Infection
• Blood Groups
• Coagulation
• Erythropoiesis
• Iron Metabolism
• Mononuclear Phagocyte System

Original Author(s): Josh Turiccki Last updated: 12th July 2022 Revisions: 24

• 1 Buffering System
• 2 Henderson-Hasselbalch Equation
• 3 How is Balance Restored?
• 4 Respiratory Responses
• 5 Clinical Relevance
• 6 Respiratory Acidosis
• 7 Respiratory Alkalosis

The acid-base balance is vital for normal bodily functions. Disruption of this equilibrium can lead to severe complications such as arrhythmias and seizures . Therefore, this balance is tightly regulated. In this article, we will look at the buffering system, responses of the respiratory system and relevant clinical conditions.

Buffering System

Blood has the ability to be resistant to small changes in pH, a characteristic known as “buffering”. This is due to the basal levels of bicarbonate and hydrogen ions in blood. The chemical reaction is given by:

Fig 1 – An equation to demonstrate the buffering system.

This reaction can be used to control pH . For example, in metabolically active tissues, there is an increase in hydrogen ions . These can react with bicarbonate in the red blood cells to form carbon dioxide which can then be exhaled by the lungs. The compensatory systems of the body rely on this equation. This will be discussed in more detail later.

Henderson-Hasselbalch Equation

The Henderson-Hasselbalch equation relates the pH to the ratio between the concentration of bicarbonate and the partial pressure of carbon dioxide. It is given by:

Fig 2 – The Henderson-Hassalbalch equation.

This shows that the ratio between bicarbonate production and partial pressure of carbon dioxide drive the pH levels of the blood. By increasing bicarbonate levels, the pH will rise and turn more alkaline . By increasing the partial pressure of carbon dioxide, the pH of blood will fall and turn acidic . The usual range of blood pH is from 7.35 to 7.45. When pH levels drop below 7.35, it is said to be acidotic, and when pH levels rise above 7.45 it is said to be alkalotic.

How is Balance Restored?

When blood pH deviates from the normal range, there are two body systems which are activated to restore equilibrium. The respiratory system alters the respiratory rate, to change the concentration of carbon dioxide in the blood, whilst the urinary system changes the reabsorption or production of bicarbonate or hydrogen ions. This is known as “compensation”.

Information on the response of the urinary system can be found here .

Respiratory Responses

There is a complex regulatory mechanism for changing the respiratory rate. Chemoreceptors detect the levels of certain molecules in the blood, and alter the respiratory rate accordingly. Peripheral chemoreceptors, in the carotid sinus and aortic arch , signal to the brain stem via cranial nerves to alter the respiratory rate. Central chemoreceptors function via a different method. When there is a rise in carbon dioxide in the blood, it can diffuse into the cerebrospinal fluid (CSF) as it is a small molecule. An enzyme called Carbonic Anhydrase can then turn carbon dioxide and water into bicarbonate and hydrogen ions. Hydrogen ions are then sensed by chemical chemoreceptors which alter the respiratory rate directly.

Further information on the role of chemoreceptors can be found here .

Clinical Relevance

Respiratory acidosis.

Respiratory acidosis is where there is an increase of carbon dioxide in the blood, the cause of which is due to a disorder in the respiratory system. Common causes include respiratory depression by opiates, disorders of the respiratory muscles such as in polio and airway obstructions such as in sleep apnoea. This overwhelms the buffering systems and causes a drop in pH. Therefore, the kidneys have to excrete more hydrogen ions (via the methods discussed previously) in addition to increasing bicarbonate reabsorption.

Respiratory Alkalosis

Respiratory alkalosis is associated with hyperventilation, which can occur due to hypoxaemia (eg. from high altitudes) or a pulmonary embolism . The compensatory methods for respiratory alkalosis is the opposite of respiratory acidosis. Due to the high levels of bicarbonate, hydrogen ions are reabsorbed to attempt to bring the pH down by decreasing hydrogen excretion and decreasing bicarbonate reabsorption and production.

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[end-clinical]

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15.5 Acid-Base Balance

Open Resources for Nursing (Open RN)

As with electrolytes, correct balance of acids and bases in the body is essential to proper body functioning. Even a slight variance outside of normal can be life-threatening, so it is important to understand normal acid-base values, as well their causes and how to correct them. The kidneys and lungs work together to correct slight imbalances as they occur. As a result, the kidneys compensate for shortcomings of the lungs, and the lungs compensate for shortcomings of the kidneys.

Arterial Blood Gases

Arterial blood gases (ABG) are measured by collecting blood from an artery, rather than a vein, and are most commonly collected via the radial artery. ABGs measure the pH level of the blood, the partial pressure of arterial oxygen (PaO2), the partial pressure of arterial carbon dioxide (PaCO2), the bicarbonate level (HCO3), and the oxygen saturation level (SaO2).

pH is a scale from 0-14 used to determine the acidity or alkalinity of a substance. A neutral pH is 7, which is the same pH as water. Normally, the blood has a pH between 7.35 and 7.45. A blood pH of less than 7.35 is considered acidic, and a blood pH of more than 7.45 is considered alkaline.

The pH of blood is a measure of hydrogen ion concentration. A low pH, less than 7.35, occurs in acidosis when the blood has a high hydrogen ion concentration. A high pH, greater than 7.45, occurs in alkalosis when the blood has a low hydrogen ion concentration. Hydrogen ions are by-products of the metabolism of substances such as proteins, fats, and carbohydrates. These by-products create extra hydrogen ions (H+) in the blood that need to be balanced and kept within normal range as described earlier.

The body has several mechanisms for maintaining blood pH. The lungs are essential for maintaining pH, and the kidneys also play a role. For example, when the pH is too low (i.e., during acidosis), the respiratory rate quickly increases to eliminate acid in the form of carbon dioxide (CO2). The kidneys excrete additional hydrogen ions (acid) in the urine and retain bicarbonate (base). Conversely, when the pH is too high (i.e., during alkalosis), the respiratory rate decreases to retain acid in the form of CO2. The kidneys excrete bicarbonate (base) in the urine and retain hydrogen ions (acid).

PaCO2 is the partial pressure of arterial carbon dioxide in the blood. The normal PaCO2 level is 35-45 mmHg. CO2 forms an acid in the blood that is regulated by the lungs by changing the rate or depth of respirations.

As the respiratory rate increases or becomes deeper, additional CO2 is removed, causing decreased acid (H+) levels in the blood and increased pH (i.e., the blood becomes more alkaline). As the respiratory rate decreases or becomes shallower, less CO2 is removed, causing increased acid (H+) levels in the blood and decreased pH (i.e., the blood becomes more acidic).

Generally, the lungs work quickly to regulate the PaCO2 levels and cause a quick change in the pH. Therefore, an acid-base problem caused by hypoventilation can be quickly corrected by increasing ventilation, and a problem caused by hyperventilation can be quickly corrected by decreasing ventilation. For example, if an anxious client is hyperventilating, they may be asked to breathe into a paper bag to rebreathe some of the CO2 they are blowing off. Conversely, a postoperative client who is experiencing hypoventilation due to the sedative effects of receiving morphine is asked to cough and deep breathe to blow off more CO2.

HCO3 is the bicarbonate level of the blood and the normal range is 22-26. HCO3 is a base managed by the kidneys and helps to make the blood more alkaline. The kidneys take longer than the lungs to adjust the acidity or alkalinity of the blood, and the response is not visible upon assessment. As the kidneys sense an alteration in pH, they begin to retain or excrete HCO3, depending on what is needed. If the pH becomes acidic, the kidneys retain HCO3 to increase the amount of bases present in the blood to increase the pH (i.e., the blood becomes alkaline). Conversely, if the pH becomes alkalotic, the kidneys excrete more HCO3, causing the pH to decrease (i.e., the blood becomes more acidic).

PaO2 is the partial pressure of arterial oxygen in the blood. It more accurately measures a client’s oxygenation status than SaO2 (the measurement of hemoglobin saturation with oxygen). Therefore, ABG results are also used to manage clients in respiratory distress.

See Table 15.5a for a review of ABG components, normal values, and key critical values. A critical ABG value means there is a greater risk of serious complications and even death if not corrected rapidly. For example, a pH of 7.10, a shift of only 0.25 below normal, is often fatal because this level of acidosis can cause cardiac or respiratory arrest or significant hyperkalemia. [1] As you can see, failure to recognize ABG abnormalities can have serious consequences for your clients.

Table 15.5a ABG Components, Descriptions, Adult Normal Values, and Critical Values [2]

Video Review of Acid-Base Balance [3]

Interpreting Arterial Blood Gases

After the ABG results are received, it is important to understand how to interpret them. A variety of respiratory, metabolic, electrolyte, or circulatory problems can cause acid-base imbalances. Correct interpretation helps the nurse and other health care providers determine the appropriate treatment and evaluate the effectiveness of interventions.

Arterial blood gasses can be interpreted as one of four conditions: respiratory acidosis, respiratory alkalosis, metabolic acidosis, or metabolic alkalosis. Once this interpretation is made, conditions can further be classified as compensated, partially compensated, or uncompensated. A simple way to remember how to interpret ABGs is by using the ROME method of interpretation, which stands for R espiratory O pposite, M etabolic E qual. This means that the respiratory component (PaCO2) moves in the opposite direction of the pH if the respiratory system is causing the imbalance. If the metabolic system is causing the imbalance, the metabolic component (HCO3) moves in the same direction as the pH. Some nurses find the Tic-Tac-Toe method of interpretation helpful. If you would like to learn more about this method, watch the video below.

Review of Tic-Tac-Toe Method of ABG Interpretation [4]

Respiratory Acidosis

Respiratory acidosis develops when carbon dioxide (CO2) builds up in the body (referred to as hypercapnia ), causing the blood to become increasingly acidic. Respiratory acidosis is identified when reviewing ABGs and the pH level is below 7.35 and the PaCO2 level is above 45, indicating the cause of the acidosis is respiratory. Note that in respiratory acidosis, as the PaCO2 level increases, the pH level decreases. Respiratory acidosis is typically caused by a medical condition that decreases the exchange of oxygen and carbon dioxide at the alveolar level, such as an acute asthma exacerbation, chronic obstructive pulmonary disease (COPD), or an acute heart failure exacerbation causing pulmonary edema. It can also be caused by decreased ventilation from anesthesia, alcohol, or administration of medications such as opioids and sedatives.

Chronic respiratory diseases, such as COPD, often cause chronic respiratory acidosis that is fully compensated by the kidneys retaining HCO3. Because the carbon dioxide levels build up over time, the body adapts to elevated PaCO2 levels, so they are better tolerated. However, in acute respiratory acidosis, the body has not had time to adapt to elevated carbon dioxide levels, causing mental status changes associated with hypercapnia. Acute respiratory acidosis is caused by acute respiratory conditions, such as an asthma attack or heart failure exacerbation with pulmonary edema when the lungs suddenly are not able to ventilate adequately. As breathing slows and respirations become shallow, less CO2 is excreted by the lungs and PaCO2 levels quickly rise.

Signs of symptoms of hypercapnia vary depending upon the level and rate of CO2 accumulation in arterial blood:

• Clients with mild to moderate hypercapnia may be anxious and/or complain of mild dyspnea, daytime sluggishness, headaches, or hypersomnolence.
• Clients with higher levels of CO2 or rapidly developing hypercapnia develop delirium, paranoia, depression, confusion, or decreased level of consciousness that can progress to seizures and coma as levels continue to rise.

Individuals with normal lung function typically exhibit a depressed level of consciousness when the PaCO2 is greater than 75 to 80 mmHg, whereas clients with chronic hypercapnia may not develop symptoms until the PaCO2 rises above 90 to 100 mmHg. [5]

When a client demonstrates signs of potential hypercapnia, the nurse should assess airway, breathing, and circulation. It is important to note that SaO2 levels may be normal with hypercapnia, and as such should not be the determining factor in further assessing acid-base issues. Urgent assistance should be sought, especially if the client is in respiratory distress. The provider will order an ABG and prescribe treatments based on assessment findings and potential causes. Treatment for respiratory acidosis typically involves improving ventilation and respiration by removing airway restrictions, reversing oversedation, administering nebulizer treatments, or increasing the rate and depth of respiration by using a BiPAP or CPAP devices. BiPAP and CPAP devices provide noninvasive positive pressure ventilation to increase the depth of respirations, remove carbon dioxide, and oxygenate the client. If these noninvasive interventions are not successful, the client will need to be intubated and placed on mechanical ventilation. [6] , [7]

Read more details about oxygenation equipment in “ Oxygen Therapy ” in Open RN Nursing Skills, 2e .

Respiratory Alkalosis

Respiratory alkalosis develops when the body removes too much carbon dioxide through respiration, resulting in increased pH and an alkalotic state. When reviewing ABGs, respiratory alkalosis is identified when pH levels are above 7.45 and the PaCO2 level is below 35. With respiratory alkalosis, notice that as the PaCO2 level decreases, the pH level increases.

Respiratory alkalosis is caused by hyperventilation that can occur due to anxiety, panic attacks, pain, fear, head injuries, or mechanical ventilation. Overdoses of salicylates and other toxins can also cause respiratory alkalosis initially and then often progress to metabolic acidosis in later stages. Acute asthma exacerbations, pulmonary embolisms, or other respiratory disorders can initially cause respiratory alkalosis as the lungs breathe faster in an attempt to increase oxygenation, which decreases the PaCO2. After a while, however, these hypoxic disorders cause respiratory acidosis as respiratory muscles tire, breathing slows, and CO2 builds up in the blood.

Clients experiencing respiratory alkalosis often report feelings of shortness of breath, dizziness or light-headedness, chest pain or tightness, paresthesias, and palpitations as a result of decreased carbon dioxide levels. [8] Respiratory alkalosis is not fatal, but it is important to recognize that underlying conditions such as an asthma exacerbation or pulmonary embolism can be life-threatening, so treatment of these underlying conditions is essential. As the pH level increases, the kidneys will attempt to compensate for the shortage of H+ ions by reabsorbing HCO3 before it can be excreted in the urine. This is a slow process, so additional treatment may be necessary.

Treatment of respiratory alkalosis involves treating the underlying cause of the hyperventilation. Acute management of clients who are hyperventilating should focus on client reassurance, an explanation of the symptoms the client is experiencing, removal of any stressors, and initiation of breathing retraining. Breathing retraining attempts to focus the client on abdominal (diaphragmatic) breathing. Read more about breathing retraining in the following box.

Breathing Retraining

While sitting or lying supine, the client should place one hand on their abdomen and the other on the chest, and then be asked to observe which hand moves with greater excursion. In hyperventilating clients, this will almost always be the hand on the chest. Ask the client to adjust their breathing so that the hand on the abdomen moves with greater excursion and the hand on the chest barely moves at all. Assure the client that this is hard to learn and will take some practice to fully master. Ask the client to breathe in slowly over four seconds, pause for a few seconds, and then breathe out over a period of eight seconds. After 5 to 10 such breathing cycles, the client should begin to feel a sense of calmness with a reduction in anxiety and an improvement in hyperventilation. Symptoms should ideally resolve with continuation of this breathing exercise.

If the breathing retraining technique is not successful in resolving a hyperventilation episode and severe symptoms persist, the client may be prescribed a small dose of a short-acting benzodiazepine (e.g., lorazepam 0.5 to 1 mg orally or 0.5 to 1 mg intravenously). Current research indicates that instructing clients who are hyperventilating to rebreathe carbon dioxide (CO2) by breathing into a paper bag can cause significant hypoxemia with significant complications, so this intervention is no longer recommended. If rebreathing is used, oxygen saturation levels should be continuously monitored. [9]

Metabolic Acidosis

Metabolic acidosis occurs when there is an accumulation of acids (hydrogen ions) and not enough bases (HCO3) in the body. Under normal conditions, the kidneys work to excrete acids through urine and neutralize excess acids by increasing bicarbonate (HCO3) reabsorption from the urine to maintain a normal pH. When the kidneys are not able to perform this buffering function to the level required to excrete and neutralize the excess acid, metabolic acidosis results.

Metabolic acidosis is characterized by a pH level below 7.35 and an HCO3 level below 22 when reviewing ABGs. It is important to notice that both the pH and HCO3 decrease with metabolic acidosis (i.e., the pH and HCO3 move in the same downward direction). A common cause of metabolic acidosis is diabetic ketoacidosis, where acids called ketones build up in the blood when blood sugar is extremely elevated. Another common cause of metabolic acidosis in hospitalized clients is lactic acidosis, which can be caused by impaired tissue oxygenation. Metabolic acidosis can also be caused by increased loss of bicarbonate due to severe diarrhea or from renal disease that causes decreased acid elimination. Additionally, toxins such as salicylate excess can cause metabolic acidosis. [10]

Nurses may first suspect that a client has metabolic acidosis due to rapid breathing that occurs as the lungs try to remove excess CO2 in an attempt to resolve the acidosis. Other symptoms of metabolic acidosis include confusion, decreased level of consciousness, hypotension, and electrolyte disturbances that can progress to circulatory collapse and death if not treated promptly. It is important to quickly notify the provider of suspected metabolic acidosis so that an ABG can be drawn, and treatment prescribed (based on the cause of the metabolic acidosis) to allow acid levels to improve. Treatment includes IV fluids to improve hydration status, glucose management, and circulatory support. When pH drops below 7.1, IV sodium bicarbonate is often prescribed to help neutralize the acids in the blood. [11] , [12]

Metabolic Alkalosis

Metabolic alkalosis occurs when there is too much bicarbonate (HCO3) in the body or an excessive loss of acid (H+ ions). Metabolic alkalosis is defined by a pH above 7.45 and an HCO3 level above 26 on ABG results. Note that both pH and HCO3 are elevated in metabolic alkalosis.

Metabolic alkalosis can be caused by gastrointestinal loss of hydrogen ions, excessive urine loss, excessive levels of bicarbonate, or a shift of hydrogen ions from the bloodstream into cells.

Prolonged vomiting or nasogastric suctioning can also cause metabolic alkalosis. Gastric secretions have high levels of hydrogen ions (H+), so as acid is lost, the pH level of the bloodstream increases.

Excessive urinary loss (due to diuretics or excessive mineralocorticoids) can cause metabolic alkalosis due to loss of hydrogen ions in the urine. Intravenous administration of sodium bicarbonate can also cause metabolic alkalosis due to increased levels of bases introduced into the body. Although it was once thought that excessive intake of calcium antacids could cause metabolic alkalosis, it has been found that this only occurs if they are administered concurrently with Kayexelate. [13]

Hydrogen ions may shift into cells due to hypokalemia, causing metabolic alkalosis. When hypokalemia occurs (i.e., low levels of potassium in the bloodstream), potassium shifts out of cells and into the bloodstream in an attempt to maintain a normal level of serum potassium for optimal cardiac function. However, as the potassium (K+) molecules move out of the cells, hydrogen (H+) ions then move into the cells from the bloodstream to maintain electrical neutrality. This transfer of ions causes the pH in the bloodstream to drop, causing metabolic alkalosis. [14]

A nurse may first suspect that a client has metabolic alkalosis due to a decreased respiratory rate (as the lungs try to retain additional CO2 to increase the acidity of the blood and resolve the alkalosis). The client may also be confused due to the altered pH level. The nurse should report signs of suspected metabolic alkalosis because uncorrected metabolic alkalosis can result in hypotension and cardiac dysfunction. [15]

Treatment is prescribed based on the ABG results and the suspected cause. For example, treat the cause of the vomiting, stop the gastrointestinal suctioning, or stop the administration of diuretics. If hypokalemia is present, it should be treated. If bicarbonate is being administered, it should be stopped. Clients with kidney disease may require dialysis. [16]

Analyzing ABG Results

Now that we’ve discussed the differences between the various acid-base imbalances, let’s review the steps to systematically interpret ABG results. Table 15.5b outlines the steps of ABG interpretation.

Table 15.5b Analyzing ABG Results [17] , [18]

• Mitchel, J. H., Wildenthal, K., & Johnson Jr., R. L. (1972). The effects of acid-base disturbances on cardiovascular and pulmonary function. Kidney International, 1 , 375-389. https://www.kidney-international.org/article/S0085-2538(15)31047-4/pdf ↵
• WakeMed Pathology Laboratories. (2016). Critical values . https://www.wakemed.org/assets/documents/pathology/lab-critical-values.pdf ↵
• Forciea, B. (2017, May 10). Acid-base balance: Bicarbonate ion buffer  [Video]. YouTube. All rights reserved. Video used with permission. https://youtu.be/5_S5wZks9v8 ↵
• RegisteredNurseRN. (2015, May 6). ABGs made easy for nurses w/ tic tac toe method for arterial blood gas interpretation  [Video]. YouTube. All rights reserved. Video used with permission. https://youtu.be/URCS4t9aM5o ↵
• Feller-Kopman, D. J., & Schwartzstein, R. M. (2020). The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure. UpToDate . https://www.uptodate.com/contents/the-evaluation-diagnosis-and-treatment-of-the-adult-patient-with-acute-hypercapnic-respiratory-failure ↵
• A.D.A.M. Medical Encyclopedia [Internet]. Atlanta (GA): A.D.A.M., Inc.; c1997-2021. Respiratory acidosis; [updated 2021, February 8]. https://medlineplus.gov/ency/article/000092.htm ↵
• Schwartzstein, R. M., Richards, J., Edlow, J. A., & Roy-Byrne, P. P. (2020). Hyperventilation syndrome in adults. UpToDate . https://www.uptodate.com/contents/hyperventilation-syndrome-in-adults ↵
• Emmett, M., & Szerlip, H. (2020). Approach to the adult with metabolic acidosis. UpToDate . https://www.uptodate.com/contents/approach-to-the-adult-with-metabolic-acidosis ↵
• A.D.A.M. Medical Encyclopedia [Internet]. Atlanta (GA): A.D.A.M., Inc.; c1997-2021. Metabolic acidosis; [updated 2021, February 8]. https://medlineplus.gov/ency/article/000335.htm ↵
• Emmett, M., & Szerlip, H. (2020). Causes of metabolic alkalosis. UpToDate . https://www.uptodate.com/contents/causes-of-metabolic-alkalosis ↵
• This work is a derivative of StatPearls by Brinkman and Sharma and is licensed under CC BY 4.0 ↵
• This work is a derivative of StatPearls by Castro and Keenaghan and is licensed under CC BY 4.0 ↵
• Woodruff, D. W. (2012). 6 easy steps to ABG analysis . Ed4Nurses, Inc. http://www.profcaseyscudmorern.org/uploads/4/5/0/4/45049193/abgebook.pdf ↵

Elevated level of carbon dioxide in the blood.

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26.4 Acid-Base Balance

Learning objectives.

By the end of this section, you will be able to:

• Identify the most powerful buffer system in the body
• Explain the way in which the respiratory system affects blood pH

Proper physiological functioning depends on a very tight balance between the concentrations of acids and bases in the blood. Acid-balance balance is measured using the pH scale, as shown in Figure 26.15 . A variety of buffering systems permits blood and other bodily fluids to maintain a narrow pH range, even in the face of perturbations. A buffer is a chemical system that prevents a radical change in fluid pH by dampening the change in hydrogen ion concentrations in the case of excess acid or base. Most commonly, the substance that absorbs the ions is either a weak acid, which takes up hydroxyl ions, or a weak base, which takes up hydrogen ions.

Buffer Systems in the Body

The buffer systems in the human body are extremely efficient, and different systems work at different rates. It takes only seconds for the chemical buffers in the blood to make adjustments to pH. The respiratory tract can adjust the blood pH upward in minutes by exhaling CO 2 from the body. The renal system can also adjust blood pH through the excretion of hydrogen ions (H + ) and the conservation of bicarbonate, but this process takes hours to days to have an effect.

The buffer systems functioning in blood plasma include plasma proteins, phosphate, and bicarbonate and carbonic acid buffers. The kidneys help control acid-base balance by excreting hydrogen ions and generating bicarbonate that helps maintain blood plasma pH within a normal range. Protein buffer systems work predominantly inside cells.

Protein Buffers in Blood Plasma and Cells

Nearly all proteins can function as buffers. Proteins are made up of amino acids, which contain positively charged amino groups and negatively charged carboxyl groups. The charged regions of these molecules can bind hydrogen and hydroxyl ions, and thus function as buffers. Buffering by proteins accounts for two-thirds of the buffering power of the blood and most of the buffering within cells.

Hemoglobin as a Buffer

Hemoglobin is the principal protein inside of red blood cells and accounts for one-third of the mass of the cell. During the conversion of CO 2 into bicarbonate, hydrogen ions liberated in the reaction are buffered by hemoglobin, which is reduced by the dissociation of oxygen. This buffering helps maintain normal pH. The process is reversed in the pulmonary capillaries to re-form CO 2 , which then can diffuse into the air sacs to be exhaled into the atmosphere. This process is discussed in detail in the chapter on the respiratory system.

Phosphate Buffer

Phosphates are found in the blood in two forms: sodium dihydrogen phosphate ( Na H 2 PO 4 Na H 2 PO 4 ), which is a weak acid, and sodium monohydrogen phosphate ( Na 2 HPO 4 Na 2 HPO 4 ), which is a weak base. When Na 2 HPO 4 Na 2 HPO 4 comes into contact with a strong acid, such as HCl, the base picks up a second hydrogen ion to form the weak acid Na H 2 PO 4 Na H 2 PO 4 and sodium chloride, NaCl. When Na HPO 4 Na HPO 4 (the weak acid) comes into contact with a strong base, such as sodium hydroxide (NaOH), the weak acid reverts back to the weak base and produces water. Acids and bases are still present, but they hold onto the ions.

Bicarbonate-Carbonic Acid Buffer

The bicarbonate-carbonic acid buffer works in a fashion similar to phosphate buffers. The bicarbonate is regulated in the blood by sodium, as are the phosphate ions. When sodium bicarbonate (NaHCO 3 ), comes into contact with a strong acid, such as HCl, carbonic acid (H 2 CO 3 ), 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.

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 ketone bodies, are acids. Carbonic acid levels in the blood are controlled by the expiration of CO 2 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, CO 2 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. However, the bicarbonate buffer is the primary buffering system of the IF 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 26.16 ). CO 2 in the blood readily reacts with water to form carbonic acid, and the levels of CO 2 and carbonic acid in the blood are in equilibrium. When the CO 2 level in the blood rises (as it does when you hold your breath), the excess CO 2 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 CO 2 . The loss of CO 2 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 CO 2 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.

The chemical reactions that regulate the levels of CO 2 and carbonic acid occur in the lungs when blood travels through the lung’s pulmonary capillaries. Minor adjustments in breathing are usually sufficient to adjust the pH of the blood by changing how much CO 2 is exhaled. In fact, doubling the respiratory rate for less than 1 minute, removing “extra” CO 2 , would increase the blood pH by 0.2. This situation is common if you are exercising strenuously over a period of time. To keep up the necessary energy production, you would produce excess CO 2 (and lactic acid if exercising beyond your aerobic threshold). In order to balance the increased acid production, the respiration rate goes up to remove the CO 2 . This helps to keep you from developing acidosis.

The body regulates the respiratory rate by the use of chemoreceptors, which primarily use CO 2 as a signal. 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 CO 2 levels rise or fall. Yet 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 CO 2 , 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 CO 2 , occurs with any cause of hyperventilation that drives off the CO 2 , such as salicylate toxicity, elevated room temperatures, fever, or hysteria.

Renal 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 CO 2 , the renal system controls the blood levels of bicarbonate. A decrease of 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 who have 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 filtrate and prevent its conservation.

Bicarbonate ions, HCO 3 - , found in the filtrate, are essential to the bicarbonate buffer system, yet the cells of the tubule are not permeable to bicarbonate ions. The steps involved in supplying bicarbonate ions to the system are seen in Figure 26.17 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.
• Step 2: The cells produce bicarbonate ions that can be shunted to peritubular capillaries.
• Step 3: When CO 2 is available, the reaction is driven to the formation of carbonic acid, which dissociates to form a bicarbonate ion and a hydrogen ion.
• Step 4: The bicarbonate ion passes into the peritubular capillaries and returns to the blood. The hydrogen ion is secreted into the filtrate, where it can become part of new water molecules and be reabsorbed as such, or removed in the urine.

It is also possible that salts in the filtrate, such as sulfates, phosphates, or ammonia, will capture hydrogen ions. If this occurs, the hydrogen ions will not be available to combine with bicarbonate ions and produce CO 2 . 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 CO 2 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 an increased reabsorption of bicarbonate by the renal system.

Disorders of the...

Acid-base balance: ketoacidosis.

Diabetic acidosis, or ketoacidosis, occurs most frequently in people with poorly controlled diabetes mellitus. When certain tissues in the body cannot get adequate amounts of glucose, they depend on the breakdown of fatty acids for energy. When acetyl groups break off the fatty acid chains, the acetyl groups then non-enzymatically combine to form ketone bodies, acetoacetic acid, beta-hydroxybutyric acid, and acetone, all of which increase the acidity of the blood. In this condition, the brain isn’t supplied with enough of its fuel—glucose—to produce all of the ATP it requires to function.

Ketoacidosis can be severe and, if not detected and treated properly, can lead to diabetic coma, which can be fatal. A common early symptom of ketoacidosis is deep, rapid breathing as the body attempts to drive off CO 2 and compensate for the acidosis. Another common symptom is fruity-smelling breath, due to the exhalation of acetone. Other symptoms include dry skin and mouth, a flushed face, nausea, vomiting, and stomach pain. Treatment for diabetic coma is ingestion or injection of sugar; its prevention is the proper daily administration of insulin.

A person who is diabetic and uses insulin can initiate ketoacidosis if a dose of insulin is missed. Among people with type 2 diabetes, those of Hispanic and African-American descent are more likely to go into ketoacidosis than those of other ethnic backgrounds, although the reason for this is unknown.

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Module 10: Fluid, Electrolyte, and Acid-Base Balance

Acid-base balance, learning objectives.

By the end of this section, you will be able to:

• Identify the most powerful buffer system in the body
• Explain the way in which the respiratory system affects blood pH

Proper physiological functioning depends on a very tight balance between the concentrations of acids and bases in the blood. Acid-balance balance is measured using the pH scale, as shown in. A variety of buffering systems permits blood and other bodily fluids to maintain a narrow pH range, even in the face of perturbations. A buffer is a chemical system that prevents a radical change in fluid pH by dampening the change in hydrogen ion concentrations in the case of excess acid or base. Most commonly, the substance that absorbs the ions is either a weak acid, which takes up hydroxyl ions, or a weak base, which takes up hydrogen ions.

Buffer Systems in the Body

The buffer systems in the human body are extremely efficient, and different systems work at different rates. It takes only seconds for the chemical buffers in the blood to make adjustments to pH. The respiratory tract can adjust the blood pH upward in minutes by exhaling CO 2 from the body. The renal system can also adjust blood pH through the excretion of hydrogen ions (H + ) and the conservation of bicarbonate, but this process takes hours to days to have an effect.

The buffer systems functioning in blood plasma include plasma proteins, phosphate, and bicarbonate and carbonic acid buffers. The kidneys help control acid-base balance by excreting hydrogen ions and generating bicarbonate that helps maintain blood plasma pH within a normal range. Protein buffer systems work predominantly inside cells.

Protein Buffers in Blood Plasma and Cells

Nearly all proteins can function as buffers. Proteins are made up of amino acids, which contain positively charged amino groups and negatively charged carboxyl groups. The charged regions of these molecules can bind hydrogen and hydroxyl ions, and thus function as buffers. Buffering by proteins accounts for two-thirds of the buffering power of the blood and most of the buffering within cells.

Hemoglobin as a Buffer

Hemoglobin is the principal protein inside of red blood cells and accounts for one-third of the mass of the cell. During the conversion of CO 2 into bicarbonate, hydrogen ions liberated in the reaction are buffered by hemoglobin, which is reduced by the dissociation of oxygen. This buffering helps maintain normal pH. The process is reversed in the pulmonary capillaries to re-form CO 2 , which then can diffuse into the air sacs to be exhaled into the atmosphere. This process is discussed in detail in the chapter on the respiratory system.

Phosphate Buffer

Phosphates are found in the blood in two forms: sodium dihydrogen phosphate ( [latex]{\text{Na}}_{2}{\text{H}}_{2}{\text{PO}}_{4}{}^{-}[/latex] ), which is a weak acid, and sodium monohydrogen phosphate ( [latex]{\text{Na}}_{\text{2}}{\text{HPO}}_{\text{4}}^{\text{2-}}[/latex] ), which is a weak base. When [latex]{\text{Na}}_{\text{2}}{\text{HPO}}_{\text{4}}^{\text{2-}}[/latex] comes into contact with a strong acid, such as HCl, the base picks up a second hydrogen ion to form the weak acid [latex]{\text{Na}}_{2}{\text{H}}_{\text{2}}{\text{PO}}_{\text{4}}{}^{-}[/latex] and sodium chloride, NaCl. When [latex]{\text{Na}}_{2}{\text{HPO}}_{\text{4}}^{2}{}^{-}[/latex] (the weak acid) comes into contact with a strong base, such as sodium hydroxide (NaOH), the weak acid reverts back to the weak base and produces water. Acids and bases are still present, but they hold onto the ions.

[latex]{\text{HCl + Na}}_{\text{2}}{\text{HPO}}_{\text{4}}\to {\text{NaH}}_{\text{2}}{\text{PO}}_{\text{4}}\text{ + NaCl}[/latex] [latex]\text{(strong acid) + (weak base) }\to \text{ (weak acid) + (salt)}[/latex] [latex]{\text{NaOH + NaH}}_{\text{2}}{\text{PO}}_{\text{4}}\to {\text{Na}}_{\text{2}}{\text{HPO}}_{\text{4}}{\text{ + H}}_{\text{2}}\text{O}[/latex] [latex]\text{(strong base) + (weak acid) }\to \text{ (weak base) + (water)}[/latex]

Bicarbonate-Carbonic Acid Buffer

The bicarbonate-carbonic acid buffer works in a fashion similar to phosphate buffers. The bicarbonate is regulated in the blood by sodium, as are the phosphate ions. When sodium bicarbonate (NaHCO 3 ), comes into contact with a strong acid, such as HCl, carbonic acid (H 2 CO 3 ), 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.

[latex]{\text{NaHCO}}_{\text{3}}\text{ + HCl }\to {\text{ H}}_{\text{2}}{\text{CO}}_{\text{3}}\text{+NaCl}[/latex] [latex]\text{(sodium bicarbonate) + (strong acid) }\to \text{ (weak acid) + (salt)}[/latex] [latex]{\text{H}}_{\text{2}}{\text{CO}}_{\text{3}}\text{ + NaOH}\to {\text{HCO}}_{\text{3-}}{\text{ + H}}_{\text{2}}\text{O}[/latex] [latex]\text{(weak acid) + (strong base)}\to \text{(bicarbonate) + (water)}[/latex]

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 CO 2 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, CO 2 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. However, the bicarbonate buffer is the primary buffering system of the IF surrounding the cells in tissues throughout the body.

Respiratory Regulation of Acid-Base Balance

Figure 1. The respiratory system can reduce blood pH by removing CO 2 from the blood.

The respiratory system contributes to the balance of acids and bases in the body by regulating the blood levels of carbonic acid. CO 2 in the blood readily reacts with water to form carbonic acid, and the levels of CO 2 and carbonic acid in the blood are in equilibrium. When the CO 2 level in the blood rises (as it does when you hold your breath), the excess CO 2 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 CO 2 . The loss of CO 2 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 CO 2 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.

The chemical reactions that regulate the levels of CO 2 and carbonic acid occur in the lungs when blood travels through the lung’s pulmonary capillaries. Minor adjustments in breathing are usually sufficient to adjust the pH of the blood by changing how much CO 2 is exhaled. In fact, doubling the respiratory rate for less than 1 minute, removing “extra” CO 2 , would increase the blood pH by 0.2. This situation is common if you are exercising strenuously over a period of time. To keep up the necessary energy production, you would produce excess CO 2 (and lactic acid if exercising beyond your aerobic threshold). In order to balance the increased acid production, the respiration rate goes up to remove the CO 2 . This helps to keep you from developing acidosis.

The body regulates the respiratory rate by the use of chemoreceptors, which primarily use CO 2 as a signal. 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 CO 2 levels rise or fall. Yet 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 CO 2 , 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 CO 2 , occurs with any cause of hyperventilation that drives off the CO 2 , such as salicylate toxicity, elevated room temperatures, fever, or hysteria.

Renal 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 CO 2 , the renal system controls the blood levels of bicarbonate. A decrease of 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 who have 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 filtrate and prevent its conservation.

Bicarbonate ions, HCO 3 − , found in the filtrate, are essential to the bicarbonate buffer system, yet the cells of the tubule are not permeable to bicarbonate ions. The steps involved in supplying bicarbonate ions to the system are seen in previous diagram 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.
• Step 2: The cells produce bicarbonate ions that can be shunted to peritubular capillaries.
• Step 3: When CO 2 is available, the reaction is driven to the formation of carbonic acid, which dissociates to form a bicarbonate ion and a hydrogen ion.
• Step 4: The bicarbonate ion passes into the peritubular capillaries and returns to the blood. The hydrogen ion is secreted into the filtrate, where it can become part of new water molecules and be reabsorbed as such, or removed in the urine.

Figure 2. Tubular cells are not permeable to bicarbonate; thus, bicarbonate is conserved rather than reabsorbed. Steps 1 and 2 of bicarbonate conservation are indicated.

It is also possible that salts in the filtrate, such as sulfates, phosphates, or ammonia, will capture hydrogen ions. If this occurs, the hydrogen ions will not be available to combine with bicarbonate ions and produce CO 2 . 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 CO 2 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 an increased reabsorption of bicarbonate by the renal system.

Disorders of the Acid-Base Balance: Ketoacidosis

Diabetic acidosis, or ketoacidosis, occurs most frequently in people with poorly controlled diabetes mellitus. When certain tissues in the body cannot get adequate amounts of glucose, they depend on the breakdown of fatty acids for energy. When acetyl groups break off the fatty acid chains, the acetyl groups then non-enzymatically combine to form ketone bodies, acetoacetic acid, beta-hydroxybutyric acid, and acetone, all of which increase the acidity of the blood. In this condition, the brain isn’t supplied with enough of its fuel—glucose—to produce all of the ATP it requires to function.

Ketoacidosis can be severe and, if not detected and treated properly, can lead to diabetic coma, which can be fatal. A common early symptom of ketoacidosis is deep, rapid breathing as the body attempts to drive off CO 2 and compensate for the acidosis. Another common symptom is fruity-smelling breath, due to the exhalation of acetone. Other symptoms include dry skin and mouth, a flushed face, nausea, vomiting, and stomach pain. Treatment for diabetic coma is ingestion or injection of sugar; its prevention is the proper daily administration of insulin.

A person who is diabetic and uses insulin can initiate ketoacidosis if a dose of insulin is missed. Among people with type 2 diabetes, those of Hispanic and African-American descent are more likely to go into ketoacidosis than those of other ethnic backgrounds, although the reason for this is unknown.

Chapter Review

A variety of buffering systems exist in the body that helps maintain the pH of the blood and other fluids within a narrow range—between pH 7.35 and 7.45. A buffer is a substance that prevents a radical change in fluid pH by absorbing excess hydrogen or hydroxyl ions. Most commonly, the substance that absorbs the ion is either a weak acid, which takes up a hydroxyl ion (OH – ), or a weak base, which takes up a hydrogen ion (H + ). Several substances serve as buffers in the body, including cell and plasma proteins, hemoglobin, phosphates, bicarbonate ions, and carbonic acid. The bicarbonate buffer is the primary buffering system of the IF surrounding the cells in tissues throughout the body. The respiratory and renal systems also play major roles in acid-base homeostasis by removing CO 2 and hydrogen ions, respectively, from the body.

Critical Thinking Questions

• Describe the conservation of bicarbonate ions in the renal system.
• Describe the control of blood carbonic acid levels through the respiratory system.
• Bicarbonate ions are freely filtered through the glomerulus. They cannot pass freely into the renal tubular cells and must be converted into CO 2 in the filtrate, which can pass through the cell membrane. Sodium ions are reabsorbed at the membrane, and hydrogen ions are expelled into the filtrate. The hydrogen ions combine with bicarbonate, forming carbonic acid, which dissociates into CO 2 gas and water. The gas diffuses into the renal cells where carbonic anhydrase catalyzes its conversion back into a bicarbonate ion, which enters the blood.
• Carbonic acid blood levels are controlled through the respiratory system by the expulsion of CO 2 from the lungs. The formula for the production of bicarbonate ions is reversible if the concentration of CO 2 decreases. As this happens in the lungs, carbonic acid is converted into a gas, and the concentration of the acid decreases. The rate of respiration determines the amount of CO 2 exhaled. If the rate increases, less acid is in the blood; if the rate decreases, the blood can become more acidic.

hypercapnia: abnormally elevated blood levels of CO 2

hypocapnia: abnormally low blood levels of CO 2

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