Understanding Acid-Base Balance and pH

• Acid-base balance is an important topic

What is pH?

• pH is a measure of the hydrogen ion concentration in a solution
• The normal blood pH is between 7.35 and 7.45
• pH = -log[H+]
• [H+] = 0.00004 mmol/L = 0.00004 mM = 0.00000004 M
• pH = 7.4 = -log[H+]
• The concentration of H+ in blood plasma is between 35-45 nanomoles/L
• For every unit change in pH, the concentration of H+ changes 10x

The Importance of H+

• H+ is highly reactive due to its large charge to size ratio, giving it a high affinity for negatively charged molecules like proteins

Sources of H+

• Acids donate protons (H+)
• Nonvolatile (fixed) acids do not leave the solution and must be excreted. E.g. sulphuric acid, phosphoric acid (from breakdown of amino and nucleic acids)
• Organic acids are metabolized rapidly so don't usually accumulate unless large amounts are produced
• Volatile acid (CO2 + H2O) can leave the solution and enter the atmosphere (i.e. lungs can breathe out carbon dioxide)

Acid Dissociation and Buffers

• Strong acids dissociate more readily than weak acids
• Weak acids are effective buffers because they can neutralize excess hydrogen ions (H+)
• They do this by binding excess hydrogen ions when pH decreases and releasing hydrogen ions as pH rises

H+ Regulation

• H+ is regulated by 3 main buffer systems: chemical, respiratory, and renal
• The bicarbonate buffer system involves the equation CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
• The sequential response to H+ load includes immediate extracellular buffering by HCO3-, respiratory buffering by decreasing CO2 (minutes to hours), intracellular buffering (two to four hours), and increased renal H+ excretion (hours to days)

Other Buffer Systems

• The phosphate buffer system operates nearly identically to the bicarbonate system
• It is composed of salts of dihydrogen phosphate (weak acid) or monohydrogen phosphate (weak base)
• It is present in relatively low concentrations in the plasma
• It is more important buffer in Intracellular Fluids (ICF) and urine

Protein Buffers

• Carboxyl groups (-COOH) can donate hydrogen ions (acting as acids)
• Amino groups (-NH2) can accept hydrogen ions, acting as bases
• Proteins are abundant in both ICF & ECF, providing a large capacity for buffering changes in pH
• Due to the diversity of amino acid side chains, proteins can act effectively across a wide range of pH values

Lungs and Kidneys

• The lungs and the kidneys are largely responsible for regulating acid-base balance, by controlling CO2 and HCO3
• CO2 production occurs during the oxidation of carbohydrates, fats, and most amino acids
• The lungs cannot handle non-volatile acids
• The kidneys can excrete acid and also reabsorb/generate bicarbonate

Bicarbonate Buffer System

• The bicarbonate buffer system is central to maintaining blood pH
• The system can resist changes in pH caused by other acids (not just CO2) and works with both the respiratory and renal systems
• Requires normal respiratory function to eliminate CO2
• Dependent on bicarbonate availability (alkaline reserve)
• Normally large alkaline reserve of NaHCO3 and HCO3 produced in kidneys

Respiratory Control

• The respiratory system controls alveolar ventilation (volume of fresh air that reaches the alveoli per minute)
• CO2 ultimately turns into H+ and breathing can provide SHORT term and IMMEDIATE control of blood pH
• When H+ decreases, CO2 accumulates through decreased ventilation (HYPOventilation)
• When H+ increases, CO2 is expelled through increased ventilation (HYPERventilation)
• Alveolar ventilation is controlled by chemoreceptors located centrally in the medulla and peripherally in the carotid body and aortic arch
• Low pH, high PCO2 and low PO2 are the main stimulators of chemoreceptors

Renal Control

• The kidneys can excrete acid load and maintain plasma HCO3 at around 24 mmol/L
• The renal system provides a LONG-TERM control of pH and can eliminate metabolic acids such as, phosphoric acid, uric acid, lactic acids, and ketones
• The most important renal mechanisms for regulating acid-base balance are reabsorption of filtered HCO3-, generation of new HCO3- by acid excretion, and formation of HCO3- by ammonium NH4+ excretion
• When the [H+] decreases in the blood, it leads to an increase in pH (alkalosis)
• The amount of free bicarbonate ions in the blood needs to reduce, as there are fewer hydrogen ions to neutralise
• When the [H+] increases in the blood, it leads to a decrease in pH (acidosis)
• To buffer this excess H+, bicarbonate ions need to be available to neutralise the hydrogen ions
• The kidneys can also excrete ammonium (NH4+)

Using Blood Values

• Blood values can determine the cause of acidosis and alkalosis
• Note the pH, where <7.35 is acidosis and >7.45 is alkalosis
• Check the pCO2 to see if there is a respiratory cause
• If respiratory acidosis is present, pCO2 >45mmHg
• If respiratory alkalosis is present, pCO2<35mmHg
• Due to rapid action of respo system, an excessively high or low pCO2 in same direction as pH = compensation
• Check the bicarbonate level if step 2 proves no resp. cause, then a metabolic condition
• If metabolic acidosis is present, <22mEq/L HCO3-
• If metabolic alkalosis is present, >26mEq/L HCO3-
• Also consider compensation. Compensation can return pH to near normal, so carefully scrutinise PCO2 or HCO3- for clues