Acid-Base Balance in Physiology

Water and Electrolytes

• Water, sodium, potassium, chloride are electrolytes crucial for bodily functions.
• Acid-base balance is vital for maintaining homeostasis.

Acid-Base Homeostasis

• Blood hydrogen ion concentration is tightly regulated.
• Normal levels are 35-45 nmol/L (pH 7.35-7.46) in extracellular fluid.
• Intracellular fluid has a slightly higher pH which is still tightly controlled.
• Normal pH for arterial blood is 7.4.
• Venous blood and interstitial fluid pH is 7.35.
• Intracellular fluid pH is 7.0.
• Alkalosis/alkalemia: arterial blood pH above 7.45.
• Acidosis/acidemia: arterial blood pH below 7.35 (physiological acidosis).

Sources of Hydrogen Ions

• Carbon dioxide transport as bicarbonate releases hydrogen ions.
• Breakdown of sulfur-containing proteins releases hydrogen ions into extracellular fluid (ECF).
• Incomplete oxidation of energy substrates (e.g., lactic acid from anaerobic respiration of glucose, organic acids and ketone bodies from fat metabolism).
• Temporary imbalances between the rates of production and consumption can occur (e.g., lactic acid accumulation during anaerobic exercise).
• Increased hydrogen ion production in disease contributes to acidosis.
• The total amount of hydrogen ions produced daily is 100,000 times greater than normal.

Hydrogen Ion Regulation

• Hydrogen ion concentration is regulated sequentially by chemical buffer systems, the respiratory center, and renal mechanisms.
• Chemical buffer systems act within seconds.
• The respiratory center (in the brain stem) acts within 1-3 minutes.
• Renal mechanisms require hours to days to effect pH changes.

Chemical Buffer Systems

• Three major chemical buffer systems: bicarbonate, phosphate, and protein buffer systems.
• These buffer systems resist any pH changes.

Buffering of Hydrogen Ions

• Buffers limit the rise in hydrogen ion concentration by combining with hydrogen ions.
• A buffer is a solution containing a weak acid or salt that can bind hydrogen ions.
• When hydrogen ions are added to a buffer, they combine with the conjugate base, forming the undissociated acid.

Buffer Solution Mechanism

• Buffers resist changes in pH when either a strong acid or base is added.
• When a strong acid is added, hydrogen ions combine with bicarbonate to form carbonic acid.
• When a strong base is added, it reacts with carbonic acid to from sodium bicarbonate.

Buffering of Hydrogen Ions (Continued)

• Buffers do not remove hydrogen ions, but temporarily neutralize excess hydrogen ions.
• Buffering is a short-term solution.
• Buffer efficiency is limited by concentration and equilibrium position.

Bicarbonate Reabsorption

• Virtually all filtered bicarbonate in kidneys is reabsorbed.
• Bicarbonate reabsorption is an indirect process that utilizes carbonic anhydrase.
• Carbon dioxide (CO2) and water (H2O) form carbonic acid (H2CO3); H2CO3 dissociates into bicarbonate and hydrogen ions (H+).
• Bicarbonate ions move from tubular cells into interstitial fluid.

Bicarbonate Reabsorption and Hydrogen Ion Excretion

• Excretion of hydrogen ions must be buffered.
• Bicarbonate reabsorption is indirect, occurring within the renal tubular cells.
• Carbonic acid forms from carbon dioxide and water, catalyzed by carbonic anhydrase.
• Bicarbonate moves into interstitial fluid with sodium ions.

Bicarbonate Buffer System (Continued)

• The capacity of the bicarbonate buffer system is limited and the bicarbonate must be regenerated.
• Excretion of hydrogen ions depends on the same reactions as bicarbonate reabsorption but is influenced by an appropriate urine buffer.

How is CO2 Exported?

• Most carbon dioxide is carried as bicarbonate.
• Dissolved carbon dioxide, carbonic acid, and carbamino compounds contribute a smaller amount to the total carbon dioxide.

Transport of Carbon Dioxide

• Aerobic metabolism produces carbon dioxide that diffuses out of cells and into Extracellular Fluid (ECF).
• A small amount combines with water to form carbonic acid.
• In red blood cells, carbon dioxide diffuses into red blood cells.
• Carbon dioxide is converted to bicarbonate inside red blood cells and is facilitated by carbonic anhydrase which enhances the conversion of carbon dioxide.
• Bicarbonate diffuses out of red blood cells in exchange for chloride ions.

Assessing Acid-Base Status

• Acid-base status is assessed by measuring bicarbonate buffer system components (water, CO2, H2CO3, H+, HCO3- (bicarbonate)).
• Excess hydrogen ions are buffered. Carbon dioxide is lost in expired air.
• Hydrogen ion concentration is proportional to PCO2.

Assessing Acid-Base Status (Continued)

• Hydrogen ion concentration in blood varies with bicarbonate concentration and PCO2 changes.
• Adding hydrogen ions, or removing bicarbonate, or increasing PCO2 increases [H+].
• Removing hydrogen ions, or adding bicarbonate, or lowering PCO2 decreases [H+].
• Normal blood [H+] is 40 nmol/L controlled by respiration and kidney function.

Disorders of Hydrogen Ion Homeostasis

• "Metabolic" acid-base disorders directly affect bicarbonate concentration.
• Insulin deficiency, buildup of ketone bodies, or bicarbonate loss from ECF can cause metabolic disorders.
• "Respiratory" acid-base disorders affect PCO2, such as impaired respiration or hyperventilation which causes a decreased PCO2.

Non-Respiratory (Metabolic) Acidosis

• Increased production or decreased excretion of hydrogen ions can cause non-respiratory acidosis.
• Causes of non-respiratory acidosis include ketoacidosis, lactic acidosis, poisoning, acid ingestion, decreased H+ excretion, and loss of bicarbonate.

Causes of Non-Respiratory Acidosis (Continued)

• Ketoacidosis (often diabetic or alcoholic).
• Lactic acid.
• Poisoning (ethanol, methanol, ethylene glycol, salicylate).
• Acid ingestion (acid poisoning).
• Renal tubular acidosis.
• Generalized renal failure.
• Carbonate anhydrase inhibitors.
• Diarrhea, pancreatic, intestinal or biliary fistulae or drainage.

Metabolic Acidosis

• Acidosis develops when hydrogen ions accumulate or bicarbonate is lost.
• Respiratory compensation occurs quickly in response to an increase in hydrogen ions concentration or a reduction in bicarbonate.

Non-Respiratory Acidosis (Further Details)

• Characterized as high [H+], low pH, low PCO2, and low [HCO3-].
• Compensation via hyperventilation, increasing CO2 removal and lowering PCO2.
• Hyperventilation is stimulated by increased [H+].

Non-Respiratory Acidosis (Continued)

• In a healthy person, hyperventilation causes respiratory alkalosis.
• Excess hydrogen ions can be excreted by the kidneys when renal function is healthy.
• Complete correction requires reversing the primary cause (e.g., rehydration or insulin for diabetic ketoacidosis).
• Hyperkalemia is common in acidotic patients.

Clinical Effects of Acidosis

• Compensatory response to metabolic acidosis is hyperventilation.
• Increased [H+] leads to increased neuromuscular irritability.
• Arrhythmias may result, particularly with hyperkalemia.

Metabolic Alkalosis (Non-Respiratory Alkalosis)

• Characterized by a primary increase in ECF bicarbonate concentration and a consequent reduction in [H+].
• Normally, increased plasma bicarbonate causes incomplete bicarbonate reabsorption and excretion in urine.
• In non-respiratory alkalosis, high renal bicarbonate reabsorption occurs, contributing factors may include decreased ECF volume, mineralocorticoid excess, increased sodium and carbonate reabsorption, and potassium depletion.
• Ingestion of massive quantities of bicarbonate can produce sustained alkalosis.

Causes of Non-Respiratory Alkalosis

• Gastrointestinal causes (gastric aspiration, vomiting with pyloric stenosis, congenital chloride-losing diarrhoea).
• Renal causes (mineralocorticoid excess; Cushing's syndrome, Conn's syndrome; drugs with mineralocorticoid activity; diuretic therapy (but not K+ sparing drugs); rapid correction of chronically high PCO2, potassium depletion).
• Administration of alkali (inappropriate treatment of acidotic states, chronic alkali ingestion).

Metabolic Alkalosis (Continued)

• Loss of hydrogen ions in the gastric fluid during vomiting, especially when there is no parallel loss of bicarbonate.
• Ingestion of absorbable alkali (sodium bicarbonate) can create alkalosis.
• Severe potassium depletion can cause hydrogen ions to be retained in cells (to replace the missing potassium), resulting in more hydrogen being exchanged for sodium reabsorption (causing acidic urine).

Clinical Effects of Metabolic Alkalosis

• Hypoventilation, confusion, eventually coma.
• Muscle cramps, tetany, and paraesthesia associated with decreased unbound plasma calcium concentration.

Metabolic Alkalosis (Correction)

• Correction of non-respiratory alkalosis requires reversal of the primary cause and maintenance mechanisms.
• The expected compensatory response is an increase in PCO2. A low arterial [H+] will inhibit the respiratory center, triggering hypoventilation and increasing PCO2.

Metabolic Alkalosis (Further Details)

• While increased PCO2 is a powerful respiratory stimulus, compensation in acute non-respiratory alkalosis may self-limit.
• In chronic disorders, significant compensation may occur because the respiratory center becomes less sensitive to carbon dioxide.
• Hypoventilation causing further hypoxemia can provide a powerful stimulus to respiratory compensation.

Management

• Management of non-respiratory alkalosis depends on the severity and cause.
• Hypovolemia is corrected simultaneously by isotonic saline infusion.
• Rapid pH correction (e.g., ammonium chloride) is only rarely necessary.
• Mild potassium depletion may require correction.

Respiratory Acidosis

• Primary disorder is an increased PCO2(CO2 retention).
• For each hydrogen ion produced, a bicarbonate ion is generated.
• The primary effect of adding hydrogen ion to a concentration of 40 nmol/l is much greater than adding one bicarbonate molecule to 26 mmol/l.
• Majority of hydrogen ions are buffered by intracellular buffers (e.g., hemoglobin).

Respiratory Acidosis (Continued)

• Renal compensation occurs slowly as the mechanisms to adjust bicarbonate reabsorption take 48-72 hours.

Respiratory Acidosis (Acute conditions)

• Acute conditions occur within minutes or hours.
• Alveolar hypoventilation leads to increased PCO2 in the blood, causing a quick rise in [H+].

Respiratory Acidosis (Further Details)

• Low PO2 and high PCO2 can cause coma.
• Examples include acute airway obstruction, choking, bronchopneumonia, acute asthma exacerbation, and depression of respiratory centers (anesthetics or sedatives).

Chronic Respiratory Acidosis

• Results from chronic obstructive airway disease and is usually a long-standing condition accompanied by maximum renal compensation.
• Primary problem in chronic respiratory acidosis is impaired alveolar oxygen ventilation.
• The kidney increases hydrogen ion excretion and ECF bicarbonate levels rise, causing a trend towards normal [H+].

Management of Acidosis

• Aim when treating respiratory acidosis is to improve alveolar ventilation and lower PCO2.
• In acute alveolar hypoventilation, hypoxia is the main threat.
• Treatment of chronic respiratory acidosis focuses on addressing the underlying cause and maximizing alveolar ventilation (physiotherapy, bronchodilators, antibiotics).

Respiratory Alkalosis

• Respiratory alkalosis is less common than acidosis but can occur from stimulated respiration.
• Acute conditions are usually present with little or no renal compensation.
• Renal compensation occurs slowly.
• Treatment is focused on inhibiting hyperventilation, which restores acid-base balance to normal levels.

Causes of Respiratory Alkalosis

• Hysterical hyperventilation.
• Mechanical overventilation of an intensive care patient.
• Raised intracranial pressure.
• Hypoxia (which stimulates the respiratory center).

Mixed Acid-Base Disorders

• Patients can have more than one acid-base disorder.
• Examples include chronic bronchitis with renal impairment (resulting in increased PCO2 and decreased bicarbonate).
• Prolonged nasogastric suction causes hyperventilation, leading to respiratory alkalosis and metabolic alkalosis.

Mixed Acid-Base Disorders (Continued)

• Two acid-base conditions can be antagonistic in affecting [H+], a metabolic acidosis with a co-existing respiratory alkalosis.
• Examples include patients with chronic obstructive airway disease with thiazide-induced potassium depletion or patients with salicylate poisoning.

Interpretation of Acid-Base Data

• A comprehensive understanding of acid-base homeostasis is essential.
• The starting point is the hydrogen ion concentration (or pH).
• A normal value does not exclude an acid-base disorder (e.g., a compensated disturbance or two primary disturbances cancelling each other out).

Interpretation of Acid-Base Data (Continued)

• Abnormal PCO2 indicates a respiratory component to the disturbance (high PCO2 in acidosis suggests respiratory acidosis; low PCO2 in acidosis suggests a non-respiratory component).
• A similar rationale applies to alkalotic states.

Case Studies (Examples)

• Provided case studies include patient history, blood gas results, and questions about acid-base disorders and assessment.
• Demonstrates application of knowledge to interpret acid-base disorders and appropriate clinical reasoning.

This quiz explores key concepts related to acid-base balance in the human body, focusing on mechanisms involving hydrogen ions, carbon dioxide, and bicarbonate. Test your knowledge on the physiological changes, enzyme functions, and disorders that influence acid-base equilibrium within the blood and lungs.