Chapter 25 – Fluid, Electrolytes & Acid-Base Balance

Body‐Fluid Distribution

• Total body water (TBW) ≈ 60\% of adult body mass (≈ 42\,\text{L} in a 70\,\text{kg} male)
  • Intracellular fluid (ICF) ≈ 2\/3 of TBW (≈ 28\,\text{L})
  • Extracellular fluid (ECF) ≈ 1\/3 of TBW (≈ 14\,\text{L})
  • Interstitial fluid (ISF) ≈ 75\% of ECF (≈ 10.5\,\text{L})
  • Plasma ≈ 25\% of ECF (≈ 3.5\,\text{L})

Factors influencing % body fluid

• Age: newborns \rightarrow 75\% TBW; elderly \rightarrow ↓ TBW (≈ 45\%) due to ↓ muscle, ↑ adipose
• Sex: males > females (testosterone maintains more skeletal muscle; estrogen promotes adipose)
• Body composition: skeletal muscle is \approx 75\% water; adipose is \approx 20\% water. ↑ adipose \rightarrow ↓ % TBW.
• Body size: larger surface area to volume (infants) \rightarrow greater insensible loss

Significance of % body‐fluid for fluid balance

• High TBW buffers rapid osmotic changes.
• Low TBW (elderly, obese) predisposes to dehydration, electrolyte shifts, drug toxicity.

Comparing ICF & ECF composition

• ICF dominant cations/anions
  • \text{K}^+ (≈ 140\,\text{mEq·L}^{-1})
  • \text{Mg}^{2+}, \text{PO}_4^{3-}, negatively charged proteins
• ECF dominant cations/anions
  • \text{Na}^+ (≈ 142\,\text{mEq·L}^{-1}), \text{Ca}^{2+}
  • \text{Cl}^-, \text{HCO}_3^-
• Osmolarities are equal (≈ 300\,\text{mOsm·kg}^{-1}); only the ionic makeup differs.

Fluid movement between compartments

• Governed by Starling forces & osmosis
  • \text{Hydrostatic}\;P pushes fluid out of plasma \rightarrow ISF.
  • \text{Colloid osmotic}\;P (proteins) pulls fluid into plasma.
  • Osmotic gradient produced by electrolyte or solute shifts drives water across cell membranes via aquaporins until equilibrium (iso‐osmotic state).

Effect of added adipose tissue

• ↑ adipose mass \rightarrow ↓ % TBW (decrease in denominator water portion); absolute water may stay constant but proportion falls.

Dehydration—net water shift

• Loss of hypotonic fluid from plasma raises ECF osmolarity \uparrow \rightarrow water moves from ICF to ECF (plasma) causing cell shrinkage.

Fluid Balance

Definition

• Fluid balance: dynamic equilibrium where fluid intake = fluid output, and water is properly distributed among compartments.

Fluid intake sources

• Preformed water (≈ 2300\,\text{mL·day}^{-1}) from beverages & food
• Metabolic water (≈ 200\,\text{mL·day}^{-1}) produced by cellular respiration: \text{C}6\text{H}{12}\text{O}6 + 6\text{O}2 \rightarrow 6\text{CO}2 + 6\text{H}2\text{O} + \text{ATP}

Water loss categories

• Sensible (measurable): urine, feces, sweat
• Insensible (unnoticed): evaporation via skin & lungs
• Obligatory: minimal urine (≈ 0.5\,\text{L}), fecal & insensible losses—independent of hydration status
• Facultative: variable urine output regulated by hormones (ADH, aldosterone, ANP)

Fluid output pathways

• Kidneys (urine) – ONLY route finely regulated
• Skin (sweat/evaporation)
• Lungs (humidified air)
• GI tract (feces)

Thirst center activation (hypothalamus)

• ↑ blood osmolarity (osmoreceptors shrink)
• ↓ blood pressure or volume (baroreceptors, RAAS \rightarrow angiotensin II)
• Dry mouth (↓ saliva)

Inhibition of thirst

• ↑ saliva, moist oral mucosa
• Stretch of stomach/SI (distension)
• ↓ osmolarity, ↑ BP/volume

Fluid Imbalances

Electrolyte Concepts

Nonelectrolyte vs Electrolyte

• Nonelectrolyte: covalent, do not dissociate (e.g., glucose, urea) \rightarrow no electrical charge.
• Electrolyte: dissociate into ions (e.g., \text{NaCl} \rightarrow \text{Na}^+ + \text{Cl}^-); conduct electricity; create osmotic gradients.

Roles in fluid balance

• Maintain osmolarity & electrical neutrality.
• Facilitate secondary active transport, neuromuscular excitability, secretion, acid–base buffering.

Six major electrolytes (besides \text{H}^+, \text{HCO}_3^-)

1. \text{Na}^+
2. \text{K}^+
3. \text{Cl}^-
4. \text{Ca}^{2+}
5. \text{PO}4^{3-} (as \text{HPO}4^{2-}, \text{H2PO}4^-)
6. \text{Mg}^{2+}

Sodium (Na$^+$)

• Primary ECF cation; chief determinant of ECF osmolarity & volume.
• Functions: neuromuscular excitability, cotransport (glucose/aa), acid–base (Na/H exchanger).
• Regulation: RAAS & ANP (renal reabsorption/excretion); ADH (water follows Na$^+$).

Potassium (K$^+$)

• Primary ICF cation; crucial for resting membrane potential.
• Distribution influenced by
  • Insulin & epinephrine (stimulate Na/K ATPase \rightarrow K$^+$ into cells)
  • Aldosterone (increases secretion into filtrate)
  • pH: ↓ pH (acidosis) \rightarrow H$^+$ moves into cells, K$^+$ moves out (hyperkalemia)

Net K$^+$ movement when pH ↓

• Direction: out of cells into ECF to buffer excess H$^+$.
• Why: exchange on H$^+$–K$^+$ antiporters maintains electroneutrality.

Chloride (Cl$^-$)

• Major ECF anion; forms HCl in stomach; follows Na$^+$.

Calcium (Ca$^{2+}$)

• 99\% in bone/teeth (hydroxyapatite); ECF \approx 2.2–2.6\,\text{mM}.
• Functions: muscle contraction, NT release, blood clotting.
• Regulation: PTH ↑ Ca$^{2+}$, calcitriol ↑ absorption, calcitonin ↓.

Phosphate (PO$^{3-}_4$)

• ICF anion; bone mineral; ATP, nucleic acids.
• Buffer in urine & ICF.
• Regulation: PTH ↑ excretion (internalization from bone); calcitriol ↑ absorption.

Magnesium (Mg$^{2+}$)

• ICF cation; cofactor >300 enzymes, stabilizes ATP.
• Regulation: renal reabsorption (loop of Henle) altered by PTH, calcitonin.

Hormonal Control of Fluid & Electrolytes

Renin–Angiotensin–Aldosterone System (RAAS)

Triggering angiotensin II formation

• ↓ BP (granular cells \rightarrow renin)
• ↓ NaCl sensed by macula densa
• Sympathetic stimulation (β$_1$ on JG cells)
  \text{Angiotensinogen} \xrightarrow[\text{renin}]{} \text{Angiotensin I} \xrightarrow[\text{ACE}]{} \text{Angiotensin II}

Four primary effects of Ang II

1. Systemic vasoconstriction (↑ TPR, ↑ BP)
2. Stimulate thirst center & ADH release
3. Stimulate aldosterone secretion (zona glomerulosa)
4. Constrict efferent arterioles (↑ GFR maintenance)

Antidiuretic Hormone (ADH / Vasopressin)

Release stimuli

• ↑ ECF osmolarity (osmoreceptors)
• ↓ BP/volume via Ang II

Three actions

1. Insert aquaporin‐2 in collecting ducts (↑ water reabsorption)
2. ↑ systemic vasoconstriction (at high [ ])
3. Stimulate thirst center

Aldosterone

Stimuli (three key)

1. ↑ K$^+$ in plasma
2. Ang II
3. ↓ Na$^+$ or ↓ BP

Renal effects

• Up‐regulates ENaC & Na/K ATPase in late DCT & CD \rightarrow Na$^+$, water reabsorption; K$^+$ & H$^+$ secretion.

Atrial Natriuretic Peptide (ANP)

• Original stimulus: atrial stretch from ↑ venous return / BP.
• Actions (3)
  1. Dilate afferent arteriole (↑ GFR) & inhibit renin
  2. Inhibit aldosterone & ADH release
  3. Increase Na$^+$ & water excretion (natriuresis/diuresis)
• Opposes effects of Ang II, ADH, aldosterone.

Comparison: ADH vs Ang II

• Both ↑ BP & thirst.
• ADH affects water only (↑ osmolarity ↓); Ang II affects both Na$^+$ and water plus potent vasoconstriction.

Acid–Base Physiology

Acid categories

1. Volatile acid: \text{H}2\text{CO}3 derived from \text{CO}_2 (excreted via lungs).
2. Fixed (non‐volatile) acids: produced by metabolism (lactic, keto, phosphoric, sulfuric) \rightarrow excreted by kidneys.

Sources of fixed acid

• Lactic acid (anaerobic respiration)
• Ketoacids (β‐oxidation, diabetes, starvation)
• Phosphoric & sulfuric acids (protein catabolism)
• Uric acid (purine breakdown)

Renal handling of H$^+$ & HCO$_3^-$

Excess H$^+$ (acidosis)

• Secrete H$^+$ (via H$^+$‐ATPase, H/K antiporter)
• Reclaim filtered HCO$_3^-$
• Generate new HCO$3^-$ via glutamine \rightarrow \text{NH}4^+ buffering.

Decreased H$^+$ (alkalosis)

• Decrease H$^+$ secretion
• Excrete excess HCO$_3^-$.

Respiratory influence on pH

• \text{CO}2 + \text{H}2\text{O} \leftrightarrow \text{H}2\text{CO}3 \leftrightarrow \text{H}^+ + \text{HCO}_3^-
• ↑ ventilation \rightarrow ↓ \text{CO}_2 ↓ H$^+$ ↑ pH.
• ↓ ventilation \rightarrow ↑ \text{CO}_2 ↑ H$^+$ ↓ pH.

Chemical Buffer Systems (first line)

1. Protein buffer (ICF & blood): side chains of amino acids
   • Acidic pH: \text{NH}2 binds H$^+$ \rightarrow \text{NH}3^+
   • Basic pH: \text{COOH} \rightarrow \text{COO}^- + \text{H}^+
2. Phosphate buffer (ICF & urine):
   \text{H}2\text{PO}4^- \leftrightarrow \text{HPO}_4^{2-} + \text{H}^+
3. Bicarbonate buffer (ECF):
   \text{HCO}3^- + \text{H}^+ \leftrightarrow \text{H}2\text{CO}3 \leftrightarrow \text{CO}2 + \text{H}_2\text{O}

Acid–Base Disturbances

Terminology

• Disturbance: initial shift in pH (respiratory or metabolic).
• Compensation: physiological response opposing disturbance (respiratory ↔ renal).
• Imbalance: persists despite max compensation.

Respiratory Disturbances

• Respiratory acidosis: ↑ \text{CO}_2 (hypoventilation, airway obstruction, COPD, opiates, brainstem injury). Infants predisposed due to narrow airways, weak muscles.
• Respiratory alkalosis: ↓ \text{CO}_2 (hyperventilation: anxiety, high altitude, fever, aspirin early).

Metabolic Disturbances

• Metabolic acidosis: ↓ HCO$_3^-$ or ↑ fixed acids (diabetic ketoacidosis, lactic acidosis, diarrhea, renal failure).
• Metabolic alkalosis: ↑ HCO$_3^-$ or ↓ H$^+$ (vomiting, diuretics, antacid overdose).

Compensation pathways

• Respiratory compensation (minutes): adjust ventilation to alter \text{CO}_2.
• Renal compensation (hours–days): adjust H$^+$ secretion & HCO$_3^-$ reabsorption.

Hyperventilation effects

• ↓ blood \text{CO}_2
• ↓ H$^+$ (alkalemia)
• ↑ pH

Compensated vs Uncompensated

• Compensated: pH normalized, but both variables (HCO$3^-$ & \text{CO}2) are deviant.
• Uncompensated: pH abnormal, no secondary change.

Key clinical Q&A

• CO$2$‐derived acid: carbonic acid (\text{H}2\text{CO}_3).
• Airway obstruction \rightarrow respiratory acidosis.
• Vomiting \rightarrow metabolic alkalosis.

Summary of Key Numbers & Equations

• Normal arterial pH: 7.35–7.45
• pKa (HCO$3^-$/CO$2$) \approx 6.1
• Henderson–Hasselbalch: \text{pH} = 6.1 + \log \frac{[\text{HCO}3^-]}{0.03\times P{\text{CO}_2}}
• Normal plasma [Na$^+$]: 135–145\,\text{mEq·L}^{-1}; [K$^+$]: 3.5–5.0\,\text{mEq·L}^{-1}; Osmolarity: 275–295\,\text{mOsm·kg}^{-1}

These notes encompass all listed learning objectives, integrating definitions, mechanisms, numerical values, and clinical correlations necessary for mastering fluid, electrolyte, and acid–base physiology.