L13 physiology

Electrolyte and Body Fluid Regulation

• Body water content varies by sex and age
  • Females have ~55% body water
  • Males have ~60% body water
  • Children have ~65% body water
  • Infants have ~75% body water
• Total body water (TBW) is ~40 liters in healthy males
• TBW in healthy females is ~35-40 liters
• Intracellular fluid (ICF) is ~25 liters (~40% of TBW)
• Extracellular fluid (ECF) is ~15 liters (~20% of TBW)

Body Fluid Compartments

• ICF: Holds ~2/3 of TBW
• Interstitial fluid: ~80% of ECF (~12 liters)
• Plasma: 20% of ECF (~3 liters)
• Transcellular fluid
  • Cerebrospinal fluid (CSF)
  • Aqueous humor of the eye
  • Synovial fluid
  • GI secretions

Distribution of Electrolytes

• ECF:
  • Major cation: Na+
  • Major anion: Cl-
• ICF:
  • Major cation: K+
  • Major anion: PO4-

Water Balance

• Water gain = Water loss
• Water gain percentages:
  • Beverages: ~60%
  • Foods: ~30%
  • Metabolism: ~10%
• Water loss percentages:
  • Urine: ~60%
  • Insensible losses (skin, lungs): ~28%
  • Feces: ~4%
  • Sweat: ~8%

Kidney Regulation of Water Loss

• ECF sodium (Na+) concentration ([Na+]) determines TBW distribution
• Water and Na+ balance are intertwined
• Kidneys regulate water through diuresis (increased urine volume)
• Kidneys regulate water through natriuresis (increased Na+ secretion)

Kidney Regulation of Water Loss Mechanisms

• Vasopressin (ADH)
• Autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR)
• Glomerulotubular Balance
• Intrinsic pressure-volume control system
• Tubular concentrating ability
• Renin-angiotensin-aldosterone system
• Natriuretic peptides

Intrinsic Pressure-Volume Control System

• A local renal mechanism
• Minimizes the effects of GFR changes on sodium and water excretion.
• Maintains a constant blood volume through pressure diuresis and pressure natriuresis
• Kidneys excrete more water and sodium when blood pressure is elevated, to maintain blood pressure and volume

Disorders of Kidney Affecting Water Balance: Diabetes Insipidus

• Central Diabetes Insipidus: Due to ADH deficiency
• Nephrogenic Diabetes Insipidus: DCT, CD unresponsive to ADH, usually due to genetic mutations affecting receptor or aquaporin 2 channel protein.

Water Gain Sensors

• Osmoreceptors (hypothalamus)
• Thirst center (hypothalamus)
• Volume receptors (atria)
• High pressure baroreceptors (carotid sinus & aortic arch)

Factors Affecting Thirst

• Plasma volume
• Plasma osmolarity
• Dry mouth/throat
• Metering of water intake by the GI tract
• Baroreceptors
• Osmoreceptors
• Angiotensin II

Disorders of Water Balance

• Dehydration
• Over-hydration

Dehydration

• Excessive loss of body water
• Mild Symptoms:
  • Thirst
  • Dry skin
  • Headache
  • Blurred vision
  • Mouth sores
  • Exhaustion
  • Irritability
  • Dizziness
  • Dark yellow urine
• Serious Symptoms:
  • Shortness of breath
  • Increased heart rate
  • Low blood pressure
• Fatal Symptoms:
  • Seizures
  • Muscle cramps
  • Kidney damage
  • Pain in joints

Dehydration Compensatory Mechanisms:

• Stimulation of thirst - ↑ Water intake
• Secretion of ADH - ↓ urine volume
• Inhibition of high pressure baroreceptors - ↑ Sympathetic tone - ↓ GFR & RBF - ↓ Urine output
• Stimulation of renin-angiotensin → ↑ Na+ reabsorption, thirst, vasoconstriction
• Secretion of aldosterone - ↑ Na+ reabsorption

Overhydration

• Too much fluid entering the body, with inadequate removal
• Neurologic: changes in level of consciousness (LOC), confusion, headache, seizures
• Respiratory: pulmonary congestion
• Cardiovascular: bounding pulse, ↑ Blood Pressure (BP), ↑ Jugular Venous Distention (JVD), presence of S3 heart sound, tachycardia
• Gastrointestinal: anorexia, nausea
• Edema: generalized swelling (dependent pitting edema)

Overhydration Compensatory Mechanisms

• Inhibition of thirst - ↓ Water intake
• Stimulation of high pressure baroreceptors - ↓ sympathetic tone - ↑ RBF & GFR - ↑ Urine output
• Inhibition of ADH, renin-angiotensin, aldosterone secretion - ↑ Urine output
• Stimulation of ANP - Natriuresis (↑ Na+ excretion in urine)

Regulating Na⁺ Balance

• Normal Na⁺ level: 135-145 mmol/L
• Hypernatremia (excess Na⁺) / Hyponatremia (low Na⁺)
• Aldosterone
• Stimulated → ↑ Na⁺ reabsorption
• Inhibited → ↓ Na⁺ reabsorption
• Renin-angiotensin mechanism
  • JG apparatus releases renin → stimulates aldosterone release.
• Atrial natriuretic peptide (ANP)
• Atrial stretch stimulates ANP release → Reduces BP and blood volume.
• Inhibits Na⁺ H₂O retention, and vasoconstriction.
• Other hormones:
  • Estrogens and Progesterone: affect Na⁺ and water balance
• Glucocorticoids: affect Na⁺ reabsorption, GFR, and edema

Regulating K⁺ Balance

• High ECF K⁺ (hyperkalemia) → increased secretion
• Stimulates aldosterone release from the adrenal cortex
  • High ECF K⁺ stimulates adrenal cortex to release aldosterone
• Aldosterone enhances K⁺ secretion.
• Renin-angiotensin mechanism is also part of K⁺ regulation

Regulating Ca²⁺ and PO₄²⁻ Balance

• Parathyroid hormone (PTH) – ↑ blood calcium level, ↑ phosphate excretion
• Calcitonin – ↓ blood calcium level

Learning Resources

• Vander's Human Physiology, 13th Edition
• Guyton and Hall: Textbook of Medical Physiology
• Moodle power-point presentations