Acid/Base

Acid-Base Disorders

Introduction

  • Presentation by Jeremiah Duby, PharmD, BCPS, BCCCP, FCCM

  • Attribution: Man and machine. Nick Veasey.

    • Website: http://www.nickveasey.com (Accessed 03.13.11)

Affiliations and Contact Information

  • University of California, Davis Medical Center

    • Clinical Pharmacy Specialist, Critical Care

    • Critical Care Residency Program Director (PGY-2)

    • Associate Clinical Professor of Medicine

  • Touro University, College of Pharmacy

    • Associate Professor, Clinical Practice

  • U.C. San Francisco, College of Pharmacy

    • Associate Professor, Pharmacy Practice

Outline of Topics

  • Basic chemistry and physiology

  • Conventional clinical assessment

  • Physicochemical model (i.e., Stewartian methodology)

  • Clinical disorders

    • Metabolic acidosis

    • Metabolic alkalosis

    • Respiratory acidosis

    • Respiratory alkalosis

  • Cases

Objectives

  • Interpret blood gas results

    • Determine if pH indicates acidemia or alkalemia.

    • Assess contributions of pulmonary or renal dysfunction to acid-base disorder.

  • Describe acid-base disorders

    • Distinguish compensation from mixed disorder based on clinical presentation.

    • Calculate anion gap from chemistry results.

    • Identify possible causes of underlying disorders.

    • Explain how hyper- and hypochloremia may account for acidemia and alkalemia.

Basic Biochemistry

  • Carbohydrate Metabolism

    • CO2 is a byproduct of energy expenditure.

  • Formation of Carbonic Acid:

    • Reaction:

    • \text{CO}2 + \text{H}2\text{O} \rightleftharpoons \text{H}2\text{CO}3 \rightleftharpoons \text{H}^+ + \text{HCO}_3^-

  • Effect of Increased CO2 on pH:

    • Increased CO2 results in increased H+ concentration, causing decreased pH.

    • Critical threshold: pH < 7.2 leads to decreased blood pressure and decreased survival.

    • Critical hormones (e.g., epinephrine, norepinephrine) lose binding affinity for receptors.

  • Role of Bicarbonate (HCO3-):

    • Acts as the principal buffer in the blood.

pH Regulation by the Lungs (via CO2)

  • Role of Red Blood Cells (RBCs)

    • Essential in gas transport (CO2, O2) between tissues and lungs.

    • Carbonic anhydrase in RBCs catalyzes the conversion of carbonic acid:

    • \text{H}2\text{CO}3 \xrightarrow{\text{RBC-carbonic anhydrase}} \text{CO}2 \text{ (dissolved)} + \text{H}2\text{O}

  • CO2 States:

    • \text{CO}2 \text{ (dissolved)} \rightleftharpoons \text{CO}2 \text{ (gas)}

    • The measured state in blood is as PCO2.

    • CO2 rapidly diffuses from tissues to RBCs and to pulmonary alveoli for expiration.

  • Respiration and CO2 Elimination:

    • Controlled by respiratory rate and tidal volume (depth of breath).

pH Regulation by the Kidneys (via HCO3-)

  • Mechanism:

    • Regulates HCO3- via elimination and absorption.

    • The kidney reabsorbs approximately 95% of HCO3- (≈5,000 mEq/d).

  • Organic and Inorganic Acid Elimination:

    • Elimination can occur directly or combined with buffers (e.g., ammonia, NH3).

pH Determination: Henderson-Hasselbalch Equation

  • Equation:
    \text{pH} = pK - \log\left(\frac{\text{acid}}{\text{base}}\right)

  • Key Points:

    • Majority of acid in plasma is carbonic acid.

    • pK for carbonic acid is 6.1.

  • Estimating H2CO3:

    • \text{H}2\text{CO}2 = ext{(measured PCO}2) \times (\text{solubility constant, } k, \text{ of CO}2 \text{ in water of 0.03})

  • Specific Example Calculation:

    • Given values:

    • PCO2 = 40 mmHg

    • HCO3- = 24 mEq/L

    • Calculation:

      • 7.4 = 6.1 - \log\left(\frac{0.03 \times 40}{24}\right)

      • Resolving leads to verifying pH balance.

Chemoreceptors and Their Role

  • Activation:

    • Stimulates respiratory responses by modulating ventilation rates and depth.

  • Peripheral Chemoreceptors:

    • Located in carotid sinus and aortic arch; triggered by:

    • Arterial acidosis (↓ pH) and alkalosis (↑ pH).

    • Hypercapnia (↑ PCO2) and hypocapnia (↓ PCO2).

    • Hypoxia (↓ PO2).

  • Central Chemoreceptors:

    • Located in brain stem; triggered by CSF acidosis.

    • Increased CO2 in CSF decreases pH and increases respiratory rate.

Compensation Mechanisms

  • Definition:

    • Expected physiological responses in one organ due to dysfunction in another organ.

  • Time Frame for Compensation:

    • Respiratory compensation: seconds to hours.

    • Metabolic compensation: days to weeks.

  • Nature of Compensation:

    • Compensation is partial: pH is not perfectly corrected.

    • Requires clinical correlation to distinguish compensation from mixed disorders in blood gas interpretation.

  • Equations:

    • Can be utilized to characterize compensation and assess the extent of compensation.

    • Helps distinguish between acute versus chronic issues.

Compensation Assessment

  • To assess compensation, clinical correlation is necessary to rule out secondary acid-base disorders in other systems:

    • Primary Disorder and Expected Compensation:

    • Respiratory Acidosis:

      • Cause: ↑ CO2 (hypercapnia)

      • Compensation: ↑ HCO3- (kidneys reabsorb more HCO3-).

    • Respiratory Alkalosis:

      • Cause: ↓ CO2 (hypocapnia)

      • Compensation: ↓ HCO3- (kidneys reabsorb less HCO3-).

    • Metabolic Acidosis:

      • Cause: ↑ organic acids → ↓ HCO3-

      • Compensation: ↑ respiratory rate, increasing CO2 elimination.

    • Metabolic Alkalosis:

      • Cause: ↓ Cl- → ↑ HCO3-

      • Compensation: ↓ respiratory rate, reducing CO2 levels.

Quick Summary of Acid-Base Regulation

  • Overall Metabolism:

    • Carbon metabolism leads to increased CO2 and subsequent decrease in pH.

  • Regulation:

    • Lungs manage PCO2 via respiratory rate and depth.

    • Kidneys manage HCO3- through reabsorption and elimination of organic acids.

  • Compensatory Responses:

    • Observed physiological responses indicate dysfunction in other organs needing clinical assessment to rule out mixed disorders.

Stewartian Methodology

  • Definition:

    • Known as strong ion or physicochemical model, this methodology explains the effects of ions on acid-base balance.

  • Strong Ions:

    • Strong ions dissociate completely at physiological pH.

    • Examples of strong cations: Na+, K+, Ca++, Mg++.

    • Examples of strong anions: Cl-, organic acids (e.g., lactate, sulfates).

  • Strong Ion Difference (SID):

    • Represents physiological cation-anion imbalances in plasma:

    • \text{SID} = (\text{Na}^+ + \text{K}^+ + \text{Ca}^{++} + \text{Mg}^{++}) - (\text{Cl}^- + \text{lactate}^-)

    • Normal value: +40 mEq/L, indicating more strong cations than strong anions.

Effective SID (SIDe)

  • Definition:

    • Represents the counter-balancing concentration of anions, indicating the charge balance in a solution.

  • Laws of Electro-neutrality:

    • This principle states that concentrations of cations must equal those of anions within permeable membranes, leading to electrical potential if imbalanced.

  • Calculation:

    • \text{SIDe} = \text{sum of weak acids}: primarily albumin (78%), phosphate (20%), with a normal ATOT of -40 mEq/L.

    • Clinical note: If SID = SIDe → pH = 7.4.

Practical Application of Acid-Base Concepts

  • Understanding Plasma Composition:

    • Plasma is the liquid component of blood, excluding red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs).

Normal Saline (NS, NaCl 0.9%) Concerns

  • Snapshot of Plasma:

    • Pre-infusion [Na+] = 140 mEq/L, [Cl-] = 100 mEq/L.

    • Post-infusion [Na+] = 154 mEq/L, [Cl-] = 154 mEq/L.

  • Misbalance:

    • Net effect leads to hyperchloremia and metabolic acidosis due to significant increases in Cl- and consequential H+ shifts leading to decreased pH.

Hyperchloremic Metabolic Acidosis

  • Cause:

    • Resulting from the administration of chloride-rich solutions (e.g., normal saline).

  • Mechanism:

    • High Cl- levels lead to shifts in cation concentration (H+ and K+), resultant acidemia, and hyperkalemia through the reduction of strong ion difference leading to augmented net negative charges (SIDe).

Metabolic Acidosis: Etiology and Causes

  • Mechanism:

    • Involves increased organic acids leading to a decrease in HCO3- and decreased pH.

    • Increased organic acid leads to an increase in H+ and HCO3- influencing H2CO2 levels.

  • Causes:

    • Loss of HCO3- via GI (e.g., diarrhea, fistulas).

    • Kidney dysfunction (impaired HCO3- reabsorption and H+ elimination).

    • Increased endogenous organic acid production or decreased elimination (lactic acidosis, diabetic ketoacidosis).

    • Iatrogenic exposure to toxic substances (e.g., alcohols, propylene glycol).

Anion Gap (AG) Role

  • Purpose:

    • Used for rapid identification of potential toxins (organic acids/toxins) causing elevated unmeasured anions (e.g., methanol, salicylates).

  • Definition:

    • AG represents the difference of unmeasured cations and anions in the plasma adhering to electro-neutrality.

    • The AG comprises unmeasured anions (e.g., albumin, organic acids, phosphate, sulfate).

Anion Gap Calculation

  • Formula:

    • \text{AG} = \text{Na}^+ - (\text{Cl}^- + \text{HCO}_3^-)

    • Note: K+ is usually omitted from calculations as its levels vary with acid-base disorders.

  • Correction for Hypoalbuminemia:

    • AG must be adjusted using:

    • \text{AG} + 2.5(\text{normal ALB} - \text{measured ALB})

  • Normal Range:

    • Typical AG values are between 6 – 12 mEq/L; AG greater than 12 mEq/L indicates an elevated anion gap situation.

Elevated AG Metabolic Acidosis Causes

  • Mechanism:

    • Guided by increased organic acids which leads to HCO3- buffer depletion.

  • Primary Causes:

    • Renal failure (accumulation of organic acids).

    • Lactic acidosis (commonly occurring in shock situations).

    • Diabetic ketoacidosis.

    • Drug intoxications (e.g., ethylene glycol, methanol, salicylates).

MUDPILES Identifying Elevated AG Metabolic Acidosis Causes

  • M: Methanol

  • U: Uremia (renal failure)

  • D: Diabetic ketoacidosis, alcoholic ketoacidosis, starvation ketoacidosis.

  • P: Propylene glycol, propofol exposure.

  • I: Isoniazid, iron overdose.

  • L: Lactic acid in shock scenarios.

  • E: Ethylene glycol, ethanol exposure.

  • S: Salicylates (aspirin).

Normal AG Metabolic Acidosis Causes

  • Mechanism:

    • Caused largely by hyperchloremia affecting the acid-base balance due to chloride-rich fluid resuscitation.

    • Reduced HCO3- level leads to a higher Cl- to HCO3- ratio.

  • Specific Causes:

    • Decreased HCO3- via lower GI losses (e.g., diarrhea, fistula output).

    • Renal tubular acidosis.

    • Use of carbonic anhydrase inhibitors (e.g., acetazolamide) causing water balance issues.

Metabolic Acidosis Treatment

  • Objective:

    • Correct underlying causes.

  • Actions for Specific Conditions:

    • For hyperchloremia: Change fluids from NaCl to balanced electrolyte solutions.

    • Dialysis may be indicated to clear toxics from the blood, primarily during acidosis or intoxications.

  • HCO3- Administration:

    • Should be considered controversial as a temporizing measure (e.g., during cardiac arrest).

    • Common treatment in chronic conditions like renal failure or diabetic ketoacidosis.

  • Compensatory Actions:

    • Increased respiratory rate to eliminate CO2 and mitigate acidosis by “breathing out” excess acid.

    • Mechanical ventilation may be warranted in acute situations.

Metabolic Alkalosis Situations

  • Saline-responsive:

    • Etiology includes hypochloremia leading to renal sparing of Cl-.

    • Common causes are GI losses (vomiting, nasogastric suctioning), diuretic use, and excessive HCO3- in resuscitation.

    • Known as “contraction alkalosis” resulting from renal excretion of Na+, Cl-, and H2O leading to decreased Cl- and increased HCO3- ratio.

  • Saline-resistant:

    • Rare occurrences are noted with normotensive hypokalemia or hypertension linked to hyperaldosteronism.

Metabolic Alkalosis Treatment

  • Correction Methods:

    • Gradually restore Cl- and fluid deficits using chloride-rich solutions (e.g., sodium chloride).

    • Caution against rapid correction, which may lead to rapid pH shifts impacting potassium balance and atrial dysrhythmias.

  • Carbonic Anhydrase Inhibitors:

    • Used for inducing HCO3- wasting by simultaneously increasing Cl- to HCO3- ratios.

    • Example: Acetazolamide promotes bicarbonate elimination and enhances Na+ and Cl- reabsorption.

  • Hydrochloric Acid (HCl):

    • Limited clinical use and only indicated for rapid correction under extreme caution.

    • Must be administered through a central venous catheter to mitigate phlebitis.

    • ABG monitoring is critical, especially for HCO3- concentrations.

Key Points - Metabolic Acid-Base Disorders

  • Metabolic Acidosis:

    • Elevated organic acids leading to decreased HCO3- and lowered pH. Causes include elevated AG conditions summarized by MUDPILES.

  • Anion Gap:

    • Important for rapid identification of potential toxins. AG is calculated as: \text{AG} = \text{Na}^+ - (\text{Cl}^- + \text{HCO}_3^-) with normal values between 6 – 12 mEq/L.

  • Hyperchloremia:

    • Causes normal AG metabolic acidosis, increasing H+ and K+ levels which lead to decreased pH leading to metabolic acidosis, accompanied by hyperkalemia.

  • Hypochloremia:

    • Causes primary metabolic alkalosis linked with decreased plasma and urine chloride levels.

  • Treatment Approaches:

    • Dialysis options for organic acid management in cases of uremia and toxic substance exposure.

    • Suitable electrolyte solutions for hyperchloremia and chloride-rich fluids for hypochloremic metabolic alkalosis.

Respiratory Acidosis

  • Etiology:

    • Caused by hypoventilation leading to increased PCO2 (hypercapnia), resulting in a decrease in pH due to:

    • \text{CO}2 + \text{H}2\text{O} \rightarrow \text{H}2\text{CO}3 \rightarrow H^+ + HCO3^-

  • Common Causes:

    • Respiratory conditions: COPD, asthmas, aspiration pneumonia.

    • Cardiopulmonary issues: ARDS, pulmonary edema, pulmonary embolism, cardiac arrest.

    • Central Nervous System (CNS) related causes: cerebrovascular accidents, obstructive sleep apnea, CNS depressant medications (opioids).

Respiratory Acidosis Treatment

  • Action Steps:

    • Target underlying causes through mechanical ventilation in cases of respiratory failure.

    • Utilize bronchodilators to alleviate obstructions (e.g., albuterol, ipratropium).

  • IV HCO3-:

    • Considered a temporary measure that does not resolve the underlying problem yet may enhance vasopressor affinity due to increased intracellular H+ binding.

Respiratory Alkalosis

  • Etiology:

    • Occurs due to increased respiratory drive leading to increased respiratory rate (hyperventilation), causing decreased PCO2 and elevated pH.

  • Causes:

    • CNS impacts such as anxiety, agitation, stimulation, and conditions like meningitis or traumatic brain injuries.

    • Pulmonary concerns like pneumonia and pulmonary edema.

    • Environmental factors including high altitude sickness.

  • General Note:

    • Respiratory alkalosis tends to be mild and transient; may frequently coexist within mixed acid-base disorders.

Respiratory Alkalosis Treatment

  • Targets:

    • Look to correct the underlying cause, i.e., infections with antibiotics or sedation for anxiety.

    • Techniques to rebreathe expired air (paper bag, rebreather mask) can stabilize CO2 levels.

    • In high altitude sickness, treatment may involve acclimatization strategies or oxygen therapy.

Key Points - Respiratory Acid-Base Disorders

  • Respiratory Acidosis:

    • Manifested through hypoventilation, leading to increased CO2 and decreased pH.

    • Common causes include chronic obstructive pulmonary disease (COPD), asthma, and CNS depressant effects. Treatment may necessitate mechanical ventilation.

  • Respiratory Alkalosis:

    • Results from hyperventilation; causes deviations such as anxiety, traumatic brain injury, and environmental factors at high altitudes. Treatment usually involves correction of the underlying anxiety or physical causes.

Step-wise Evaluation of Acid-Base Status

To diagnose and manage acid-base disorders, follow these steps:

  1. Identify blood gas results: pH, PCO2, PaO2, HCO3-.

  2. Recognize the primary disorder based on pH values:

    • Alkalemia indicated by pH > 7.4,

    • Acidemia indicated by pH < 7.4.

  3. Assess CO2 contribution:

    • Evaluate if CO2 is ↑ (indicating respiratory acidosis) or ↓ (indicating respiratory alkalosis).

  4. Assess HCO3- contribution:

    • Determine if HCO3- is ↑ (metabolic alkalosis) or ↓ (metabolic acidosis).

  5. Evaluate possible compensation, confirming clinical correlations needed to rule out secondary acid-base disorder in other systems.

  6. Formulate a clinical assessment incorporating the primary disorder, aetiology, and expected compensation.

Summary of Normal Values for Arterial Blood Gas (ABG)

  • ABG composition: pH/aCO2/PaO2/HCO3-

  • pH Range: 7.35 – 7.45

  • PCO2 Range: 35 – 45 mmHg

    • High PCO2 indicates hypercapnia leading to lowered pH.

    • Low PCO2 results in an increased pH.

  • PO2 Range: 90 – 100 mmHg

    • Oxygen inerts do not affect pH directly; lack of PO2 denotes hypoxemia.

  • HCO3- Range: 22 – 26 mEq/L

    • Elevated HCO3- leads to an increase in pH, while reduced HCO3- causes a decrease in pH.

Further Step-wise Assessment of Blood Gases

  • Based on blood gas results, the evaluation process involves identifying primary acid-base disorders, analyzing potential contributions by PCO2 and HCO3-, and assessing compensatory mechanisms.

  1. Assessing PCO2 and HCO3- Independently: Analyze whether CO2 is contributing positively or negatively to the primary pH abnormality as indicated by expected ratios.

  2. Compensation: Requires correllating whether compensation indicates a secondary disorder.

    • Report any mismatched clinical symptomatology alongside acid-base assessment findings.

Final Considerations

  • Understand CO2 Influence: CO2 serves as a substrate for acid formation:

    • Formation of carbonic acid via:

    • \text{CO}2 + \text{H}2\text{O} \rightleftharpoons \text{H}2\text{CO}3 \rightleftharpoons H^+ + HCO3^-

    • Importance of the pH regulating mechanism across the respiratory and metabolic spectrum to maintain homeostasis in physiological state.

  • Role of Bicarbonate (HCO3-): Identified as the principal buffer leading to shifted pH states depending on level variations, demonstrating its significant influence on acid-base homeostasis.

  • Final Note on pH as an Indicator: Overall reflects the net function and balance of both respiratory and metabolic activities highlighting the PCO2 to HCO3- ratio's impact on biological systems.