Page 1: Sodium and Water Composition of Body Fluids

Total Body Water

• Water Composition: Comprises ~50% of body weight in women and ~60% in men.

• Water Distribution:

  • Intracellular Fluid (ICF): 55–75% of total body water.

  • Extracellular Fluid (ECF): 25–45%, further subdivided into:

    • Intravascular (Plasma Water)

    • Extravascular (Interstitial Space)

  • The distribution ratio of intravascular to extravascular space is approximately 1:3.

Fluid Movement and Starling Forces

• Fluid Exchange: Movement occurs across the capillary wall, determined by:

  • Capillary Hydraulic Pressure

  • Colloid Osmotic Pressure

• Fluid Dynamics:

  • Transcapillary hydraulic pressure gradient favors the ultrafiltration of plasma into the extravascular space.

  • Return of fluid to the intravascular compartment happens via lymphatic flow.

Osmolality and Cell Membranes

• Osmolality Defined: The concentration of solutes in a fluid, expressed in mOsm/kg of water.

• Diffusion Across Membranes: Water diffuses easily across most cell membranes to achieve osmotic equilibrium (ECF osmolality = ICF osmolality).

• Major Solutes:

  • ECF: Predominantly Na+, Cl−, and HCO3−.

  • ICF: Predominantly K+ and organic phosphates (ATP, creatine phosphate).

• Tonicity: Determined by solutes that restrict movement across compartments; ineffective osmoles like urea do not lead to water shifts.

Water Balance Regulation

• Maintaining Osmolality: Vasopressin (AVP) secretion, water intake, and renal water transport are critical to maintaining osmolality (280–295 mOsm/kg).

• Vasopressin Production:

  • Synthesized in the hypothalamus and released from the posterior pituitary.

  • Activation of central osmoreceptor neurons allows sensing of circulating osmolality.

• Osmotic Threshold for AVP Release:

  • Stimulated at ~285 mOsm/kg; thirst sensation activated simultaneously.

  • AVP secretion modulated by blood volume and blood pressure changes.

Clinical Relevance of ECF Volume

• ECF Volume Modulation: ECF volume affects the relationship between osmolality and AVP release.

  • Hypovolemia: Decreases the osmotic threshold and increases the slope of the response curve.

  • Hypervolemia: Increases the osmotic threshold and decreases the slope.

• Half-life of AVP: 10–20 minutes in circulation, ensuring rapid adjustments to body fluid homeostasis.

Page 2: Vasopressin Mechanisms and Renal Function

Figure 53-1: AVP Levels

• AVP Response to Osmolality: Detectable in healthy individuals at ~285 mOsm/kg; linearly correlated above this level.

• Factors Affecting AVP Levels: Volume status significantly modulates this relationship; hypovolemia reduces the osmotic threshold.

Renal Role in Water Balance

• Excretion and Retention of Water: Controlled by circulating AVP.

• V2-Receptor Activation: AVP acts on renal V2-type receptors, enhancing water reabsorption via:

  • Increased intracellular cAMP levels.

  • Activation of protein kinase A-dependent phosphorylation of transport proteins.

Countercurrent Mechanism

• Thick Ascending Limb of Henle: Key part of renal concentrating mechanism; increases medullary osmolality promoting water absorption.

• Renal Urea Transport: Crucial for generating the medullary osmotic gradient enabling solute-free water excretion.

Water Reabsorption Within the Kidney

• Aquaporin Channels: AVP-induced insertion of AQP2 channels increases water permeability.

• Urine Concentration:

  • Under antidiuretic conditions, kidneys can excrete concentrated urine (up to 1200 mOsm/kg).

  • Absence of AVP leads to dilute urine (30–50 mOsm/kg).

  • Disorders affecting this mechanism include diabetes insipidus, affecting aquaporin insertion.

Page 3: Renal Transport Mechanisms and Na+ Regulation

Sodium and Water Transport

• Role of Sodium: Actively pumped by Na+/K+-ATPase; most Na+ is extracellular, affecting ECF volume.

• Renal Functions: Filtration at glomeruli followed by sequential reabsorption by renal tubules.

Sodium Reabsorption Mechanics

• Reabsorption Sites:

  • Proximal Tubule: Reabsorbs ~66% of filtered Na+.

  • Thick Ascending Limb: Reabsorbs 25–30% via Na+–K+–2Cl− cotransporter.

• Distal Nephron: Fine-tunes Na+–Cl− excretion, involving thiazide-sensitive and aldosterone-sensitive mechanisms.

  • Principal cells utilize ENaC channels for Na+ reabsorption.

Sodium Transport Diagram

• Transport Mechanisms: Shows principal and intercalated cell functioning alongside Na+ and K+ channels involved in sodium and potassium transport processes.

Page 4: Sodium Homeostasis and Extracellular Volume

Maintenance of Circulatory Integrity

• Renal Na+ Management: Key to arterial perfusion and overall circulatory integrity.

• Neurohumoral Responses: Activated under "underfilling" conditions lead to Na+ retention, increasing vascular resistance.

Hypovolemia: Definition and Causes

• Hyponatremia: True volume depletion combining salt and water loss, categorized into renal and nonrenal origins.

• Renal Causes: Include osmotic diuresis due to solute load, mineralocorticoid deficiency, and acute tubular injury.

Page 5: Nonrenal Causes of Hypovolemia and Diagnostic Suggestions

Nonrenal Causes of Hypovolemia

• Fluid Loss Mechanisms:

  • Gastrointestinal (vomiting, diarrhea)

  • Insensible skin and respiratory loss.

  • Third spacing due to capillary permeability changes.

Diagnostic Evaluation Focus

• History and Physical Exam: Key to identify liquid losses and ensuing symptoms.

• Laboratory Analysis: Chemistry tests to assess urea, creatinine, electrolytes for volume assessment and underlying pathologies.

• Signs of Hypovolemia: Include decreased JVP, tachycardia, hypotension, etc.

Page 6: Clinical Evaluation and Management Strategies

Management of Hypovolemia

• Restoration Goals: Aim for normovolemia and managing ongoing losses.

• Initial Treatment: Mild cases can be managed with oral fluids; more severe requires IV therapy.

Sodium Disorders Overview

• Volume Status Interaction: Alters serum Na+ concentration and water homeostasis fundamentally alters blood pressure profiles.

• Hyponatremia Classification:

  • Hypovolemic: Loss of fluids from multiple sources.

  • Euvolemic: Isolated water retention without ECF contraction.

  • Hypervolemic: High total body Na+ but with excessive dilute body fluids.

Page 7: Hyponatremia Mechanisms and Assessment

Hyponatremia Groups by Underlying Mechanisms

• Neurohumoral Activation Effects:

  • Increased AVP level leads to kidney retention of water, lowering sodium.

• Clinical Approach to Hyponatremia: History of water intake, fluid loss conditions, and additional clinical signs.

Urine Examination in Hyponatremia

• Urine Na+ and Osmolality Measurements: Critical for elucidating causes and underlying pathological states.

• Diagnostic Strategies: follow established guidelines to discern volume status and underlying abnormal physiology.

Page 8: Chronic and Acute Hyponatremia Management

Management of Chronic Hyponatremia

• Therapeutic Approaches: address the underlying cause is key; usual treatment involves careful fluid management and dietary adjustments.

• Caution with Correction: Particularly with chronic cases, rapid changes in Na+ levels can provoke ODS or other complications.

Long-Term Considerations in Hyponatremia Management

• Monitoring: Continuous reassessment required for safe sodium correction; presence of symptoms dictates alterations in treatment plans.