Acid-Base Balance – Anatomy, Mechanism, Functions

Acid-base balance is the homeostatic regulation of the pH of the body’s extracellular fluid (ECF).[1] The proper balance between the acids and bases (i.e. the pH) in the ECF is crucial for the normal physiology of the body—and for cellular metabolism.[1] The pH of the intracellular fluid and the extracellular fluid need to be maintained at a constant level.

The body’s balance between acidity and alkalinity is referred to as acid-base balance. The blood’s acid-base balance is precisely controlled because even a minor deviation from the normal range can severely affect many organs. The body uses different mechanisms to control the blood’s acid-base balance.

The three-dimensional structures of many extracellular proteins, such as the plasma proteins and membrane proteins of the body’s cells, are very sensitive to the extracellular pH.[rx][rx] Stringent mechanisms, therefore, exist to maintain the pH within very narrow limits. Outside the acceptable range of pH, proteins are denatured (i.e. their 3-D structure is disrupted), causing enzymes and ion channels (among others) to malfunction.

pH, Buffers, Acids, and Bases

Henderson–Hasselbalch equation

The Henderson–Hasselbalch equation when applied to the carbonic acid-bicarbonate buffer system in the extracellular fluids, states that:[rx]

{\displaystyle \mathrm {pH} =\mathrm {p} K_{\mathrm {a} ~\mathrm {H} _{2}\mathrm {CO} _{3}}+\log _{10}\left({\frac {[\mathrm {HCO} _{3}^{-}]}{[\mathrm {H} _{2}\mathrm {CO} _{3}]}}\right),}

where:

  • pH is the negative logarithm (or cologarithm) of molar concentration of hydrogen ions in the ECF.
  • pKa H2CO3 is the cologarithm of the acid dissociation constant of carbonic acid. It is equal to 6.1.
  • [HCO
    3]
     is the molar concentration of bicarbonate in the blood plasma
  • [H2CO3] is the molar concentration of carbonic acid in the ECF.

However, since the carbonic acid concentration is directly proportional to the partial pressure of carbon dioxide ({\displaystyle P_{{\mathrm {CO} }_{2}}}) in the extracellular fluid, the equation can be rewritten as follows:[rx][rx]{\displaystyle \mathrm {pH} =6.1+\log _{10}\left({\frac {[\mathrm {HCO} _{3}^{-}]}{0.0307\times P_{\mathrm {CO} _{2}}}}\right),}

where:

  • pH is the negative logarithm of molar concentration of hydrogen ions in the ECF.
  • [HCO
    3]
     is the molar concentration of bicarbonate in the plasma
  • PCO2 is the partial pressure of carbon dioxide in the blood plasma.

The pH of the extracellular fluids can thus be controlled by the regulation of PCO2 and other metabolic acids.

Acids dissociate into H+ and lower pH, while bases dissociate into OH and raise pH; buffers can absorb these excess ions to maintain pH.

Key Points

A basic solution will have a pH above 7.0, while an acidic solution will have a pH below 7.0.

Buffers are solutions that contain a weak acid and its a conjugate base; as such, they can absorb excess H+ ions or OH ions, thereby maintaining an overall steady pH in the solution.

pH is equal to the negative logarithm of the concentration of H+ ions in solution: pH = −log[H+].

Key Terms

  • alkaline: having a pH greater than 7; basic
  • acidic: having a pH less than 7
  • buffer: a solution composed of a weak acid and its conjugate base that can be used to stabilize the pH of a solution

Self-Ionization of Water

Hydrogen ions are spontaneously generated in pure water by the dissociation (ionization) of a small percentage of water molecules into equal numbers of hydrogen (H+) ions and hydroxide (OH) ions. The hydroxide ions remain in solution because of their hydrogen bonds with other water molecules; the hydrogen ions, consisting of naked protons, are immediately attracted to un-ionized water molecules and form hydronium ions (H30+). By convention, scientists refer to hydrogen ions and their concentration as if they were free in this state in liquid water.

2H2O⇋H3O++OH−

The concentration of hydrogen ions dissociating from pure water is 1 × 10−7 moles H+ ions per liter of water. The pH is calculated as the negative of the base 10 logarithm of this concentration:

pH = −log[H+]

The negative log of 1 × 10−7 is equal to 7.0, which is also known as neutral pH. Human cells and blood each maintain near-neutral pH.

pH Scale

The pH of a solution indicates its acidity or basicity (alkalinity). The pH scale is an inverse logarithm that ranges from 0 to 14: anything below 7.0 (ranging from 0.0 to 6.9) is acidic, and anything above 7.0 (from 7.1 to 14.0) is basic (or alkaline ). Extremes in pH in either direction from 7.0 are usually considered inhospitable to life. The pH in cells (6.8) and the blood (7.4) are both very close to neutral, whereas the environment in the stomach is highly acidic, with a pH of 1 to 2.

The pH scale: The pH scale measures the concentration of hydrogen ions (H+) in a solution.

Non-neutral pH readings result from dissolving acids or bases in water. Using the negative logarithm to generate positive integers, high concentrations of hydrogen ions yield a low pH, and low concentrations a high pH.

An acid is a substance that increases the concentration of hydrogen ions (H+) in a solution, usually by dissociating one of its hydrogen atoms. A base provides either hydroxide ions (OH) or other negatively-charged ions that react with hydrogen ions in solution, thereby reducing the concentration of H+ and raising the pH.

Strong Acids and Strong Bases

The stronger the acid, the more readily it donates H+. For example, hydrochloric acid (HCl) is highly acidic and completely dissociates into hydrogen and chloride ions, whereas the acids in tomato juice or vinegar do not completely dissociate and are considered weak acids; conversely, strong bases readily donate OH and/or react with hydrogen ions. Sodium hydroxide (NaOH) and many household cleaners are highly basic and give up OH rapidly when placed in water; the OH− ions react with H+ in solution, creating new water molecules and lowering the amount of free H+ in the system, thereby raising the overall pH. An example of a weak basic solution is seawater, which has a pH near 8.0, close enough to neutral that well-adapted marine organisms thrive in this alkaline environment.

Buffers

How can organisms whose bodies require a near-neutral pH ingest acidic and basic substances (a human drinking orange juice, for example) and survive? Buffers are the key. Buffers usually consist of a weak acid and its conjugate base; this enables them to readily absorb excess H+ or OH, keeping the system’s pH within a narrow range.

Maintaining a constant blood pH is critical to a person’s well-being. The buffer that maintains the pH of human blood involves carbonic acid (H2CO3), bicarbonate ion (HCO3), and carbon dioxide (CO2). When bicarbonate ions combine with free hydrogen ions and become carbonic acid, hydrogen ions are removed, moderating pH changes. Similarly, excess carbonic acid can be converted into carbon dioxide gas and exhaled through the lungs; this prevents too many free hydrogen ions from building up in the blood and dangerously reducing its pH; likewise, if too much OH is introduced into the system, carbonic acid will combine with it to create bicarbonate, lowering the pH. Without this buffer system, the body’s pH would fluctuate enough to jeopardize survival.

image

Buffers in the body: This diagram shows the body’s buffering of blood pH levels: the blue arrows show the process of raising pH as more CO2 is made; the purple arrows indicate the reverse process, lowering pH as more bicarbonate is created.

Antacids, which combat excess stomach acid, are another example of buffers. Many over-the-counter medications work similarly to blood buffers, often with at least one ion (usually carbonate) capable of absorbing hydrogen and moderating pH, bringing relief to those that suffer “heartburn” from stomach acid after eating.

Chemical Buffer Systems

Chemical buffers, such as bicarbonate and ammonia, help keep the blood’s pH in the narrow range that is compatible with life.

Key Points

The body’s acid-base balance is tightly regulated to keep the arterial blood pH between 7.38 and 7.42. Buffer solutions keep the pH constant in a wide variety of chemical actions.

A buffer solution is a mixture of a weak acid and its conjugate base, or a weak base and its conjugate acid.

The bicarbonate buffering system maintains optimal pH levels and regulates the carbon dioxide concentration that, in turn, shifts any acid-base imbalance.

Renal physiology controls pH levels through several powerful mechanisms that excrete excess acid or base.

Key Terms

  • bicarbonate: An alkaline, vital component of the pH buffering system of the human body that maintains acid-base homeostasis.
  • buffer: A solution used to stabilize the pH (acidity) of a liquid.
  • pH: In chemistry, a measure of the activity of the hydrogen ion concentration.

EXAMPLES

Anything that adversely affects an individual’s bloodstream will have a negative impact on that individual’s health since the blood acts as a chemical buffer solution to keep all the body’s cells and tissues properly balanced.

Acid-Base Homeostasis

Acid-base homeostasis concerns the proper balance between acids and bases; it is also called body pH. The body is very sensitive to its pH level, so strong mechanisms exist to maintain it. Outside an acceptable range of pH, proteins are denatured and digested, enzymes lose their ability to function, and death may occur.

Buffer Solution

A buffer solution is an aqueous solution of a weak acid and its conjugate base, or a weak base and its conjugate acid. Its pH changes very little when a small amount of strong acid or base is added to it. Buffer solutions are used as a means of keeping pH at a nearly constant value in a wide variety of chemical applications.

Many life forms thrive only in a relatively small pH range, so they utilize a buffer solution to maintain a constant pH. One example of a buffer solution found in nature is blood. The body’s acid-base balance is normally tightly regulated, keeping the arterial blood pH between 7.38 and 7.42.

Several buffering agents that reversibly bind hydrogen ions and impede any change in pH exist. Extracellular buffers include bicarbonate and ammonia, whereas proteins and phosphates act as intracellular buffers.

The bicarbonate buffering system is especially key, as carbon dioxide (CO2) can be shifted through carbonic acid (H2CO3) to hydrogen ions and bicarbonate (HCO3−):

H2O+CO2⇋H2CO3⇋H++CO3−

Acid–base imbalances that overcome the buffer system can be compensated in the short term by changing the rate of ventilation. This alters the concentration of carbon dioxide in the blood and shifts the above reaction according to Le Chatelier’s principle, which in turn alters the pH.

Renal Physiology

The kidneys are slower to compensate, but renal physiology has several powerful mechanisms to control pH by the excretion of excess acid or base. In response to acidosis, the tubular cells reabsorb more bicarbonate from the tubular fluid, and the collecting duct cells secrete more hydrogen and generate more bicarbonate, and ammonia genesis leads to an increase of the NH3 buffer.

In its responses to alkalosis, the kidneys may excrete more bicarbonate by decreasing hydrogen ion secretion from the tubular epithelial cells, and lower the rates of glutamine metabolism and ammonium excretion.

This chart shows the pH range of a variety of common fluids. Buffering agents keep blood pH between 7.38 and 7.42. Sulfuric acid (batter acid) has the highest acidity on the chart; distilled water and saliva are neutral; and lye has the highest alkalinity on the chart.

pH range: Buffering agents keep blood pH between 7.38 and 7.42.

Regulation of H+ by the Lungs

Acid-base imbalances in the blood’s pH can be altered by changes in breathing to expel more COand raise pH back to normal.

Key Points

Hydrogen ions (H+) are carried in the blood along with oxygen and carbon dioxide.

Sixty percent of the carbon dioxide is carried as dissolved bicarbonate.

A small amount of carbon dioxide is carried on the hemoglobin as carbaminohemoglobin, which is transported to the lungs for removal.

Following Le Chatelier’s principle, an imbalance in pH is returned to normal by increasing the rate of ventilation in the lungs.

To compensate for acidemia, more CO2 is expelled, while the opposite occurs for alkalemia.

Key Terms

  • carbaminohemoglobin: A compound of hemoglobin and carbon dioxide. It is one of the forms in which carbon dioxide exists in the blood.
  • Le Chatelier’s principle: A principle that states that if a chemical system at equilibrium experiences a change in concentration, temperature, or total pressure, the equilibrium will shift in order to minimize that change.

EXAMPLES

Since maintaining normal pH is vital for life, and since the lungs play a critical role in maintaining normal pH, smokers have yet another reason to quit smoking.

Acid-base imbalance occurs when a significant insult causes the blood pH to shift out of its normal range (7.35 to 7.45). An excess of acid in the blood is called acidemia and an excess of base is called alkalemia.

The process that causes the imbalance is classified based on the etiology of the disturbance (respiratory or metabolic) and the direction of change in pH ( acidosis or alkalosis). There are four basic processes and one or a combination may occur at any given time.

  • Metabolic acidosis
  • Respiratory acidosis
  • Metabolic alkalosis
  • Respiratory alkalosis

Blood carries oxygen, carbon dioxide, and hydrogen ions (H+) between tissues and the lungs. The majority of CO2 transported in the blood is dissolved in plasma (60% is dissolved bicarbonate).

This is a diagram of expiration that shows a person exhaling. When blood pH drops too low, the body compensates by increasing breathing to expel more carbon dioxide.

Expiration: When blood pH drops too low, the body compensates by increasing breathing to expel more carbon dioxide.

A smaller fraction is transported in the red blood cells that combine with the globin portion of hemoglobin as carbaminohemoglobin. This is the chemical portion of the red blood cell that aids in the transport of oxygen and nutrients around the body, but, this time, it is carbon dioxide that is transported back to the lung.

Acid-base imbalances that overcome the buffer system can be compensated in the short term by changing the rate of ventilation. This alters the concentration of carbon dioxide in the blood, shifting the above reaction according to Le Chatelier’s principle, which in turn alters the pH. The basic reaction governed by this principle is as follows:

H2O+CO2⇋H2CO3⇋H++CO3−

When the blood pH drops too low (acidemia), the body compensates by increasing breathing to expel more CO2; this shifts the above reaction to the left such that less hydrogen ions are free; thus, the pH will rise back to normal. For alkalemia, the opposite occurs.

The Role of the Kidneys in Acid-Base Balance

The kidneys help maintain the acid–base balance by excreting hydrogen ions into the urine and reabsorbing bicarbonate from the urine.

Key Points

The kidneys maintain homeostasis through the excretion of waste products.

Acidosis causes more bicarbonate to be reabsorbed from the tubular fluid, while the collecting ducts secrete more hydrogen to generate more bicarbonate, and more NH3 buffer is formed.

Alkalosis causes the kidney to excrete more bicarbonate as there is reduced secretion of hydrogen ions and more ammonium is excreted.

Key Terms

  • base: Any of a class of generally water-soluble compounds, that have a bitter taste, turn red litmus paper blue, and react with acids to form salts.
  • renal: Pertaining to the kidneys.

EXAMPLES

Urine testing is important because it can detect acid-base imbalances. For instance, uncontrolled diabetes results in highly acidic urine. If diabetes remains uncontrolled, the kidneys could become over-stressed and malfunction, which could lead to coma or death.

Within the human body, fluids such as blood must be maintained within the narrow range of 7.35 to 7.45, making it slightly alkaline. Outside that range, pH becomes incompatible with life; proteins are denatured and digested, enzymes lose their ability to function, and the body is unable to sustain itself.

To maintain this narrow range of pH the body has a powerful buffering system. Acid-base imbalances that overcome this system are compensated in the short term by changing the rate of ventilation.

Kidneys and Acid-Base Balance

The kidneys have two very important roles in maintaining the acid-base balance:

  1. They reabsorb bicarbonate from urine.
  2. They excrete hydrogen ions into urine.

The kidneys are slower to compensate than the lungs, but renal physiology has several powerful mechanisms to control pH by the excretion of excess acid or base. The major, homeostatic control point for maintaining a stable pH balance is renal excretion.

Bicarbonate (HCO3−) does not have a transporter, so its reabsorption involves a series of reactions in the tubule lumen and tubular epithelium. In response to acidosis, the tubular cells reabsorb more bicarbonate from the tubular fluid, and the collecting duct cells secrete more hydrogen and generate more bicarbonate, and ammonia genesis leads to an increase in the formation of the NH3 buffer.

In response to alkalosis, the kidneys may excrete more bicarbonate by decreasing hydrogen ion secretion from the tubular epithelial cells, and lowering the rates of glutamine metabolism and ammonium excretion.

Organ Systems Involved

Every organ system of the human body relies on pH balance; however, the renal system and the pulmonary system are the two 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 combining with water, the amount of carbon dioxide expired can cause pH to increase or decrease. When the respiratory system is utilized to compensate 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.

Function

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 of the partial pressure of oxygen to 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 that there is 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 makeup 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:

  • H20 + CO2 <-> H2CO3<-> H+ + HCO3-

The Le Chatelier Principle states that when the variables of concentration, pressure, or temperature are changed, a system in equilibrium will react accordingly to restore a new steady state. The reaction above, states that if more hydrogen ions are produced, the equation will shift 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 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 CO2 to restore equilibrium.[rx]

What’s normal?

A normal range for arterial pH is 7.35 to 7.45. Acidosis is a pH less than 7.35; alkalosis is a pH greater than 7.45. Because pH is measured in terms of hydrogen (H+) ion concentration, an increase in H+ ion concentration decreases pH and vice versa. Changes in H+ ion concentration can be stabilized through several buffering systems: bicarbonate-carbonic acid, proteins, hemoglobin, and phosphates.

Acidosis, therefore, can be described as a physiologic condition caused by the body’s inability to buffer excess H+ ions. At the other end, alkalosis results from a deficiency in H+ ion concentration. Acidemia and alkalemia refer to the process of acidosis or alkalosis, respectively, occurring in arterial blood.

Body acids are formed as end products of cellular metabolism. Under normal physiologic conditions, a person generates 50 to 100 mEq/day of acid from the metabolism of carbohydrates, proteins, and fats. In addition, the body loses base in the stool. In order to maintain acid-base homeostasis, acid production must balance the neutralization or excretion. The lungs and kidneys are the main regulators of acid-base homeostasis. The lungs release CO2, an end product of carbonic acid (H2CO3). The renal tubules, with the regulation of bicarbonate (HCO3), excrete other acids produced from the metabolism of proteins, carbohydrates, and fats.

Reference values for arterial blood

Women Men
cH+P 36.3–41.7 nmol l−1 (pH: 7.38–7.44) 37.2–42.7 nmol l−1 (pH: 7.37–7.43)
ctH+Ecf −2.3–+2.7 mmol l−1 −3.2–+1.8 mmol l−1
pCO2 4.59–5.76 kPa (33.8–42.4 mmHg) 4.91–6.16 kPa (36.8–46.2 mmHg)
cHCO3P 21.2–27.0 mmol l−1 22.2–28.3 mmol l−1

cH+P: conc. of (free) hydrogen ion in plasma; ctH+Ecf: conc. of titratable hydrogen ion in extracellular fluid (also called standard base deficit, SBD); pCO2: tension of carbon dioxide; cHCO3P: conc. of bicarbonate in plasma.

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 pH, pC02, pO2, HCO3, oxygen saturation, and more. This allows the physician to understand the status of the patient better. ABGs are especially important in 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
  • pCO2 = 35 to 45 mmHg
  • pO2 = 75 to 100 mmHg
  • HCO3- = 22 to 26 mEq/L
  • O2 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
  • PaCO2 level determines respiratory contribution; a high level means the respiratory system is lowering the pH and vice versa.
  • HCO3- level denotes metabolic/kidney effect. An elevated HCO3- is raising the pH and vice versa.
  • If the pH is acidotic, look for the number that corresponds with a lower pH. If it is a respiratory acidosis, the CO2 should be high. If the patient is compensating metabolically, the HCO3- should be high as well. Metabolic acidosis will be depicted with an HCO3- that is low.
  • If the pH is alkalotic, again, determine which value is causing this. A respiratory alkalosis will mean the CO2 is low; a metabolic alkalosis should lend an HCO3- that is high. Compensation with either system will be reflected oppositely; for a respiratory alkalosis the metabolic response should be a low HCO3- and for metabolic alkalosis, the respiratory response should be a high CO2.
  • If the pH level is in the physiological range but the PaCO2 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 the information that can be used to determine the exact mechanism of the acid-base imbalance as well as the factors contributing to the disorders.[rx][rx]

References