Acid-Base Balance During Exercise – Chapter 11

Acids, Bases, and pH

• Definition of an acid
  • Molecule that can liberate H^+
  • Raises the [H^+] in solution, therefore lowers pH
  • Examples
  • Lactic acid (strong acid) \text{pH} = 3.51
  • Hydrochloric acid (very strong) \text{pH} = 1.1
• Definition of a base
  • Molecule capable of combining with H^+
  • Lowers [H^+], therefore raises pH
  • Example: Bicarbonate (\text{HCO}_3^-), a strong base with \text{pH} = 8.3
• pH concept
  • Expresses [H^+] in solution on a logarithmic scale
  • \text{pH} = -\log_{10}[H^+]
  • Pure water: [H^+] = 1 \times 10^{-7}\,\text{M} \Rightarrow \text{pH} = 7.0 (neutral)
  • Each pH unit represents a 10-fold change in [H^+]
• pH scale reference points (selected examples)
  • Hydrochloric acid ≈ 1
  • Lemon juice / gastric juice ≈ 2–3
  • Wine ≈ 2.4–3.5
  • Tomato juice ≈ 4.7
  • Urine ≈ 6
  • Human blood ≈ 7.4 (slightly alkaline)
  • Seawater ≈ 8
  • Household ammonia ≈ 10.5–11
  • Sodium hydroxide ≈ 14

Physiological pH Values & Terminology

• Normal arterial blood: \text{pH} = 7.40 \pm 0.05
• Normal skeletal muscle (rest): \text{pH} = 7.04\text{–}7.17
• Survival range for arterial blood: 7.0 \le \text{pH} \le 7.8
• Acidosis: \text{pH} < 7.4
• Alkalosis: \text{pH} > 7.4
• Typical [H^+] and pH across body fluids (selected)
  • Arterial blood: 4.0 \times 10^{-5}\,\text{mEq·L}^{-1} \rightarrow \text{pH} = 7.40
  • Venous blood / interstitial fluid: 7.35
  • Intracellular fluid: \text{pH} = 6.0\text{–}7.4 (depends on metabolic state)
  • Urine: \text{pH} = 4.5\text{–}8.0
  • Gastric HCl: \text{pH} \approx 0.8

Conditions Leading to Systemic Acid–Base Disorders

• Metabolic acidosis
  • High-intensity exercise (rapid, transient)
  • Long-term starvation → production of keto-acids from fat metabolism
  • Uncontrolled diabetes → diabetic ketoacidosis
• Metabolic alkalosis
  • Severe vomiting (loss of gastric acid)
  • Certain kidney diseases (excessive acid loss or bicarbonate retention)

Hydrogen-Ion Production During Exercise

• Three primary biochemical sources of H^+
  1. CO$_2$ formation during oxidative metabolism of carbohydrate, fat & protein
  • \text{CO}2 + \text{H}2O \leftrightarrow \text{H}2CO3 \leftrightarrow H^+ + \text{HCO}_3^-
  1. Lactic acid / lactate production from anaerobic glycolysis
  2. ATP hydrolysis
  • \text{ATP} + \text{H}2O \rightarrow \text{ADP} + \text{HPO}4^{2-} + H^+
• Distribution of buffering capacity at rest: ≈ 60–70 % of total chemical buffering is intracellular, mainly via cellular proteins

Sport-Specific Risk of Acid–Base Disturbance

• Events lasting ≥ 45 s accumulate significant H^+
• Highest risk sports (high anaerobic load)
  • 100 m swim, 400 m & 800 m run
• Moderate-high risk: 1,500 m run, 5,000 m run
• Low risk: baseball, football, marathon, weightlifting (low-rep), volleyball, etc.
• Competitive strategy matters: maximal final sprint or playing “all-out” exponentially increases risk regardless of sport

Performance Consequences of Acidosis

• Elevated [H^+] inhibits key metabolic enzymes of glycolysis and oxidative phosphorylation → reduced ATP production
• H^+ competes with Ca^{2+} on troponin binding sites → impaired cross-bridge cycling and weaker muscle contraction
• Net effect: earlier fatigue, diminished power, lower endurance

Acid–Base Buffer Systems

• General buffer principle
  • If pH is high (alkaline): buffer donates H^+
  • If pH is low (acidic): buffer accepts H^+
• Intracellular buffers
  • Proteins (especially those with histidine residues)
  • Phosphate groups (e.g., \text{HPO}4^{2-} / \text{H}2PO_4^-)
  • Bicarbonate
• Extracellular buffers
  • Bicarbonate
  • Hemoglobin (H^+ + \text{Hb} \leftrightarrow \text{HHb})
  • Plasma proteins
• Bicarbonate–carbonic acid system
  • Central chemical buffer in plasma and interstitial fluid
  • Enzyme carbonic anhydrase catalyzes \text{CO}_2 hydration in RBCs & muscle
  • Henderson–Hasselbalch equation
    \text{pH} = pKa + \log{10}\left( \dfrac{[\text{HCO}3^-]}{[\text{H}2\text{CO}_3]} \right)
• Additional chemical buffers (Table view)
  • Phosphate buffer converts strong acids into weaker acids
  • Protein buffers accept H^+ via histidine imidazole ring (pK_a ≈ 6.1)
  • Histidine-dipeptides (mainly carnosine) serve as rapid intracellular buffers

Skeletal-Muscle–Specific Buffering & Transport

• Intracellular buffering contributions during exercise
  • ≈ 60 % proteins, 20–30 % bicarbonate, 10–20 % phosphates
• Transporters that move acid equivalents to the extracellular space
  • NHE (Na$^+$/H$^+$ exchanger): exports H^+ in exchange for Na^+
  • MCT (monocarboxylate transporter): co-transports lactate and H^+ out of the fiber

Influence of Fiber Type & Training on Buffering

• Fast-twitch (Type II) fibers naturally possess higher buffering capacity than slow-twitch (Type I) fibers
• High-intensity interval or sprint training increases
  • Intramuscular carnosine content
  • Density/activity of H^+ transporters (NHE, MCT)
  • Overall capacity to resist exercise-induced pH decline in both trained & previously untrained individuals

Ergogenic Strategies: Sodium & Nutritional Buffers

• Sodium bicarbonate / sodium citrate ("alkaline salts")
  • Elevate extracellular bicarbonate → greater gradient for H^+ efflux
  • Documented to extend time to exhaustion at 80–120 % \dot V!O_2\,\text{max} in some studies; others show no effect (individual variability)
  • Side-effects: gastrointestinal distress (nausea, vomiting), risk of metabolic alkalosis, potential prohibition by governing bodies
• Beta-alanine supplementation
  • \beta-alanine + histidine → carnosine synthesis in muscle
  • Carnosine (β-alanyl-L-histidine) concentrations typically 5–8 mmol·L$^{-1}$ (wet) or 20–30 mmol·kg$^{-1}$ (dry)
  • Comparable to ATP, carnitine; higher in Type II fibers (e.g., gastrocnemius > soleus)
  • Boosts intracellular buffering and performance in events of 1–4 min duration
  • Major side-effect: paresthesia (tingling), dose-dependent and benign
• Sodium citrate
  • Similar to bicarbonate in effect and limitations; optimal for 2–4 min events

Carnosine: Detailed Biochemistry & Significance

• Dipeptide discovered by Vladimir Gulevich (1900); name derives from Latin "carnis" (meat)
• Effective pK_a of histidine imidazole ring (≈ 6.1) matches physiological intracellular pH (6.5–7.1), making it an ideal dynamic buffer during exercise-induced acidosis
• Constitutes a major portion of the total intramyocellular buffering system together with proteins, phosphates, ammonia, bicarbonate
• Factors influencing muscle carnosine content
  • Muscle fiber type (Type II > Type I)
  • Training status
  • Sex, age, vegetarian vs omnivore diet
  • β-alanine supplementation (strongest acute modulator)

Respiratory Regulation of pH

• Rapid second-line defense mechanism
• When arterial pH decreases (↑[H^+]), reaction shifts left as lungs "blow off" CO2, thereby reducing H^+ and raising pH \text{CO}2 + \text{H}2O \leftrightarrow \text{H}2\text{CO}3 \leftrightarrow H^+ + \text{HCO}3^-
• Hyperventilation during intense exercise constitutes "respiratory compensation" for metabolic acidosis

Renal Regulation of Acid–Base Balance

• Kidneys are crucial for long-term pH homeostasis (hours–days)
  • Reclaim or excrete bicarbonate to adjust blood buffer pool
  • ↓ blood pH → ↓ bicarbonate excretion (retain base)
  • ↑ blood pH → ↑ bicarbonate excretion (lose base)
• Minimal contribution during short-term exercise due to slow response time

Acid–Base Dynamics During Graded Exercise

• Determinants of H^+ load: intensity, muscle mass recruited, duration
• Observed trends with increasing % \dot V!O_2\,\text{max}
  • Muscle pH falls sooner & more steeply than arterial blood pH (muscle has lower buffer capacity)
  • Arterial blood bicarbonate concentration declines in parallel with rising blood lactate
• Representative data
  • At \approx 75\% \dot V!O_2max: arterial pH may reach ~7.20; muscle pH may approach ~6.6

Integrated Lines of Defense Against Exercise-Induced pH Shifts

1. First-line (within muscle fibers)
   • Cellular buffers: proteins, phosphates, bicarbonate, carnosine
   • Immediate chemical neutralization of H^+
2. First-line (in blood)
   • Extracellular buffers: bicarbonate predominant; hemoglobin & plasma proteins auxiliary
3. Second-line
   • Continued blood buffering as H^+ leaves muscle via NHE & MCT
   • Respiratory compensation: increased ventilation removes CO_2

Practical / Ethical Considerations

• Buffer supplementation must balance potential ergogenic benefits against side-effects, individual variability, and governing-body regulations
• Over-alkalosis can impair performance, highlighting the importance of controlled dosing and athlete monitoring
• Understanding fiber-type differences & training interventions allows tailored strategies to enhance natural buffering (e.g., HIIT for middle-distance runners, β-alanine for sprinters)
• Clinical relevance: insights into acid-base handling guide treatment of metabolic acidosis in diabetes, renal disease, and critical care settings