Premed · Premed · Anatomy Physiology 2

Lecture 20: Fluid, Electrolyte, and Acid-Base Balance

Anatomy and Physiology II

Learning Objectives

By the end of this lecture, students will be able to:

1. Describe the distribution of body fluids across compartments and the factors governing fluid movement between them
2. Explain the regulation of water balance and the roles of ADH and thirst
3. Describe the regulation of major electrolytes (Na+, K+, Ca2+) and their clinical significance
4. Define acid, base, and pH and describe the body's buffer systems
5. Explain the roles of the respiratory and renal systems in maintaining acid-base balance
6. Interpret acid-base disorders: respiratory and metabolic acidosis and alkalosis

Lecture Content

I. Body Fluid Compartments

Total body water (TBW) constitutes approximately 60% of body weight in an average adult male and about 50% in females, who have a higher proportion of body fat. For a 70 kg male, TBW is approximately 42 liters.

Body water is distributed between two major compartments. The intracellular fluid (ICF) accounts for approximately two-thirds of TBW (about 28 liters) and represents the fluid inside cells. Its major cation is potassium, and its major anions are phosphate and proteins. The extracellular fluid (ECF) makes up approximately one-third of TBW (about 14 liters) and encompasses all fluid outside cells. Its major cation is sodium, and its major anions are chloride and bicarbonate. The ECF is further subdivided into plasma (intravascular fluid, approximately 3 liters) within the blood vessels, interstitial fluid (approximately 11 liters) between cells in the tissues, and transcellular fluid (a small volume of about 1 liter) including cerebrospinal fluid, synovial fluid, aqueous humor, and pleural, pericardial, and peritoneal fluids.

Fluid Movement Between Compartments

Movement between plasma and interstitial fluid is governed by Starling forces at the capillary level. Hydrostatic pressure pushes fluid out of the capillary while osmotic pressure pulls fluid in, producing net filtration at the arteriolar end and net reabsorption at the venular end. Excess interstitial fluid is returned to the circulation via the lymphatic system. Movement between ECF and ICF is governed by osmosis, with water moving freely across cell membranes via aquaporins driven by differences in osmolarity between the two compartments. Cells shrink (crenate) in hypertonic ECF and swell (lyse) in hypotonic ECF. Normal plasma osmolarity ranges from approximately 275 to 295 mOsm/L.

II. Water Balance

Daily water intake averages approximately 2,500 mL, derived from ingested liquids (about 1,500 mL), food moisture (about 750 mL), and metabolic water produced by cellular respiration (about 250 mL). Daily water output matches intake at approximately 2,500 mL, distributed among urine (about 1,500 mL, the regulated component), insensible losses from the skin and lungs (about 900 mL), sweat (variable, potentially several liters during exercise or heat exposure), and feces (about 100 mL).

Water balance is regulated by several mechanisms. ADH (antidiuretic hormone, or vasopressin) is released from the posterior pituitary when plasma osmolarity increases (detected by hypothalamic osmoreceptors) or when blood volume and pressure decrease (detected by baroreceptors). ADH increases water reabsorption in the collecting duct by inserting AQP2 channels, resulting in decreased urine output and concentrated urine. The thirst mechanism is driven by the hypothalamic thirst center, which is stimulated by increased plasma osmolarity, decreased blood volume or pressure, dry mouth, and angiotensin II. Aldosterone promotes sodium reabsorption, with water following osmotically, while ANP promotes sodium and water excretion.

<image>A multi-panel diagram of body fluid compartments and water balance. Panel A: A human body outline divided to show the fluid compartments as proportional boxes — ICF (2/3 of TBW, ~28 L) shown in one color with major ions (K+, HPO4 2-, proteins listed inside), and ECF (1/3 of TBW, ~14 L) subdivided into plasma (~3 L) and interstitial fluid (~11 L) in different shades with major ions (Na+, Cl-, HCO3-). Arrows between compartments indicate water movement by osmosis (ICF-ECF) and Starling forces (plasma-interstitial). Panel B: A balance scale showing daily water intake on one side (ingested liquids 1500 mL, food 750 mL, metabolic water 250 mL) and water output on the other (urine 1500 mL, insensible loss 900 mL, feces 100 mL). Panel C: A flowchart of the ADH response to dehydration — increased plasma osmolarity detected by hypothalamic osmoreceptors, stimulating ADH release from the posterior pituitary, leading to AQP2 insertion in collecting duct cells, increased water reabsorption, decreased urine volume, and restoration of normal osmolarity (negative feedback).</image>

III. Electrolyte Balance

Sodium (Na+)

Sodium is the most abundant ECF cation, with a normal plasma concentration of 135 to 145 mEq/L, and is the primary determinant of ECF osmolarity and volume. Its regulation involves several hormones. Aldosterone increases sodium reabsorption in the DCT and collecting duct, retaining sodium and water to increase ECF volume. ANP inhibits sodium reabsorption to promote natriuresis. Angiotensin II stimulates sodium reabsorption in the PCT and triggers aldosterone release.

Hyponatremia (sodium below 135 mEq/L) causes the ECF to become hypotonic, driving water into cells and producing cellular swelling that can lead to cerebral edema, confusion, and seizures. Causes include excessive water intake, SIADH, diuretic use, and severe vomiting or diarrhea. Hypernatremia (sodium above 145 mEq/L) causes the ECF to become hypertonic, pulling water out of cells and causing cellular shrinkage that manifests as thirst, confusion, and seizures. Causes include dehydration, diabetes insipidus, and excessive salt intake.

Potassium (K+)

Potassium is the major ICF cation, with a normal plasma concentration of 3.5 to 5.0 mEq/L. It is critical for the resting membrane potential, nerve impulse conduction, and muscle contraction, particularly of cardiac muscle. Approximately 98% of potassium is intracellular, maintained by the Na+/K+ ATPase. Aldosterone stimulates potassium secretion by principal cells in the collecting duct, and elevated plasma potassium directly stimulates aldosterone release from the adrenal cortex. Insulin and epinephrine shift potassium into cells by stimulating the Na+/K+ ATPase. Acid-base status also affects potassium distribution: acidosis causes potassium to shift out of cells (as hydrogen ions enter via H+/K+ exchange), producing hyperkalemia, while alkalosis has the opposite effect.

Hypokalemia (potassium below 3.5 mEq/L) produces muscle weakness, cardiac arrhythmias (flattened T wave, U wave), and paralytic ileus. Hyperkalemia (potassium above 5.0 mEq/L) produces cardiac arrhythmias (peaked T waves, widened QRS), potentially fatal ventricular fibrillation, and constitutes a medical emergency.

Calcium (Ca2+)

Normal plasma calcium concentration ranges from 8.5 to 10.5 mg/dL total, with approximately 50% in the ionized (active) form. Calcium is essential for muscle contraction, neurotransmitter release, blood clotting, and bone structure. Parathyroid hormone (PTH), released in response to low plasma calcium, increases bone resorption through osteoclast activity, increases calcium reabsorption in the DCT, and stimulates calcitriol production in the kidney to enhance intestinal calcium absorption. Calcitonin from thyroid C cells is released in response to high calcium and inhibits osteoclast activity, though it plays a minor role in adults. Calcitriol (1,25-dihydroxyvitamin D) increases intestinal calcium absorption.

Hypocalcemia increases neuromuscular excitability, causing muscle spasms, tetany, laryngospasm, and cardiac arrhythmias, and is assessed clinically by Trousseau sign and Chvostek sign. Hypercalcemia decreases neuromuscular excitability, producing muscle weakness, constipation, kidney stones, and cardiac arrhythmias, remembered clinically as "stones, bones, groans, and moans."

IV. Acid-Base Balance

Fundamentals

An acid is a proton (H+) donor and a base is a proton acceptor. pH equals the negative logarithm of the hydrogen ion concentration, and normal arterial blood pH ranges from 7.35 to 7.45. A pH below 7.35 constitutes acidemia (acidosis), while a pH above 7.45 constitutes alkalemia (alkalosis). Even small pH changes profoundly affect enzyme activity, protein structure, and cellular function. The body produces large amounts of acid daily in two forms: volatile acid in the form of CO2 from metabolism, which combines with water to form carbonic acid that dissociates into hydrogen ions and bicarbonate and is eliminated by the lungs, and non-volatile (fixed) acids including sulfuric acid, phosphoric acid, lactic acid, and ketoacids, which are eliminated by the kidneys.

Chemical Buffer Systems (Immediate Response — Seconds)

Chemical buffers resist pH changes by binding or releasing hydrogen ions. The bicarbonate buffer system is the most important in the ECF, operating through the reaction: CO2 + H2O reversibly forms H2CO3, which reversibly forms H+ + HCO3-. If hydrogen ion concentration rises, bicarbonate buffers it by forming carbonic acid, which breaks down to CO2 that is exhaled. If hydrogen ion concentration falls, carbonic acid dissociates to provide hydrogen ions. This system is particularly effective because both CO2 (regulated by the lungs) and bicarbonate (regulated by the kidneys) can be independently adjusted. The phosphate buffer system (HPO4 2- + H+ reversibly forms H2PO4-) is important in the ICF and renal tubular fluid. The protein buffer system is the most abundant intracellular buffer, with hemoglobin in red blood cells serving as a major blood protein buffer and amino acid side chains accepting or donating hydrogen ions.

Respiratory Regulation (Minutes to Hours)

The respiratory system regulates blood pH by controlling CO2 elimination through the relationship: CO2 + H2O reversibly forms H2CO3, which reversibly forms H+ + HCO3-. In acidosis (low pH), central and peripheral chemoreceptors are stimulated, increasing ventilation rate and depth (hyperventilation) so that more CO2 is blown off, hydrogen ion concentration decreases, and pH rises. In alkalosis (high pH), ventilation decreases (hypoventilation), CO2 is retained, hydrogen ion concentration increases, and pH falls. Respiratory compensation can correct pH by approximately 75% within minutes but cannot correct respiratory acid-base disorders since the lungs themselves are the problem.

Renal Regulation (Hours to Days — Slowest but Most Powerful)

The kidneys regulate pH through three mechanisms. First, they excrete hydrogen ions through type A intercalated cells (via H+ ATPase and H+/K+ ATPase) and PCT cells (via the Na+/H+ exchanger). Second, they reabsorb bicarbonate: virtually all filtered bicarbonate is reclaimed, mainly in the PCT, through a process in which secreted hydrogen ions combine with filtered bicarbonate in the lumen to form carbonic acid, which is converted to CO2 and water by brush border carbonic anhydrase. The CO2 diffuses into the cell and is used to regenerate bicarbonate intracellularly, which is then transported to the blood. Third, the kidneys generate new bicarbonate when hydrogen ions are excreted bound to urinary buffers such as phosphate or ammonia. In the ammonium excretion pathway, glutamine is metabolized in PCT cells to produce ammonium and bicarbonate; the ammonium is excreted in urine while the new bicarbonate is added to the blood. In acidosis, the kidneys increase hydrogen ion secretion, ammonium production, and bicarbonate reabsorption. In alkalosis, the kidneys decrease hydrogen ion secretion and excrete more bicarbonate.

<image>A comprehensive diagram of acid-base regulation. Panel A: The three lines of defense shown as a timeline — chemical buffers (seconds), respiratory compensation (minutes to hours), and renal compensation (hours to days). Panel B: The bicarbonate buffer system equation (CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-) with arrows showing that the lungs regulate the CO2 side and the kidneys regulate the HCO3- side. A see-saw balance is depicted with H+ concentration on the fulcrum, CO2 on one side and HCO3- on the other; the normal 20:1 ratio of HCO3-:CO2 that maintains pH 7.4 is shown. Panel C: A nephron cell diagram showing renal H+ secretion and HCO3- reabsorption in the PCT — luminal H+ secretion via Na+/H+ exchanger, combination of H+ with filtered HCO3- to form CO2 + H2O (catalyzed by brush border carbonic anhydrase), CO2 diffusing into the cell, intracellular carbonic anhydrase regenerating HCO3- which exits basolaterally into the blood. Panel D: Ammonium excretion pathway — glutamine entering the PCT cell, being metabolized to NH4+ and HCO3-, NH4+ secreted into the tubular lumen, and new HCO3- added to the peritubular blood.</image>

V. Acid-Base Disorders

Interpreting Arterial Blood Gases (ABGs)

Normal values are pH 7.35 to 7.45, pCO2 35 to 45 mmHg, and HCO3- 22 to 26 mEq/L. Interpretation follows three steps: first, determine whether the pH indicates acidosis or alkalosis; second, determine whether the primary cause is respiratory (abnormal pCO2) or metabolic (abnormal HCO3-); third, look for compensation, in which the other value moves in the same direction as the pH change. The anion gap, calculated as Na+ minus (Cl- + HCO3-), is normally 8 to 12 mEq/L. An elevated anion gap metabolic acidosis indicates the presence of unmeasured acids such as ketoacids, lactic acid, uremic toxins, or toxic ingestions (remembered by the MUDPILES mnemonic). A normal anion gap metabolic acidosis indicates bicarbonate loss, as seen in diarrhea or renal tubular acidosis.

VI. Clinical Correlations

Dehydration occurs when water loss exceeds water intake, increasing osmolarity and triggering ADH release and thirst, which produce concentrated urine. Edema is excess interstitial fluid caused by increased capillary hydrostatic pressure (heart failure), decreased albumin and oncotic pressure (liver disease), or sodium retention (renal failure). Diabetic ketoacidosis (DKA) results from a lack of insulin leading to uncontrolled lipolysis, excess ketone body production, and high anion gap metabolic acidosis, with Kussmaul breathing (deep, rapid respirations) serving as respiratory compensation. Renal tubular acidosis involves defects in renal hydrogen ion secretion or bicarbonate reabsorption, producing normal anion gap metabolic acidosis. Respiratory failure is the inability to maintain adequate ventilation, causing CO2 retention and respiratory acidosis.

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