---

---

PATHOPHYSIOLOGY - ALTERATIONS IN FLUIDS, ELECTROLYTES, AND ACID-BASE BALANCE

---

LEARNING OBJECTIVES

1. Etiology and pathogenesis of dehydration (diarrhea, vomiting)
2. Causes and mechanisms of edema + clinical application
3. Common electrolyte imbalances: Na+, K+, Ca2+
4. Mechanisms of respiratory and metabolic acid-base disturbances

---

PART 1: COMPOSITION AND COMPARTMENTAL DISTRIBUTION OF BODY FLUIDS

Role of Body Fluids

• Transport gases (O2, CO2), nutrients, metabolic wastes
• Generate electrical activity powering nerve impulses and muscle contractions
• Participate in energy metabolism (food → usable energy)

Total Body Water (TBW)

• Healthy adult = ~60% of body weight (~42 L in a 70 kg person)
• Homeostasis: volume and composition remain relatively constant - but disease and environmental stress disrupt regulatory mechanisms
• TBW varies: Infants ~75%; fat tissue is low in water, so obese and female individuals have lower TBW %

Fluid Compartments

ECF Subdivisions:

Electrolyte Composition

• ECF: Large Na+, Cl-; moderate HCO3-; small K+
• ICF: Large K+; small Na+, Cl-, HCO3-
• Clinically measured electrolytes (serum/blood) reflect ECF levels
• The Na+/K+/ATPase pump maintains this gradient: pumps 3 Na+ OUT, 2 K+ IN per cycle using ATP

Mechanisms of Fluid Movement

Osmotic Pressure

• Pressure needed to oppose water movement across a semipermeable membrane
• Water moves from low → high solute concentration
• Normal serum osmolality = 280-295 mOsm/kg

Tonicity (Effective Osmolality) - KEY

• Hypotonic environment → water enters cells → cellular swelling
• Hypertonic environment → water leaves cells → cellular dehydration/shrinkage
• Isotonic environment → no net water movement

Starling Forces (Capillary Exchange Diagram):

• Net filtration = (Pc - Pi) - (πc - πi)
• Arterial end: net filtration (fluid out); Venous end: net reabsorption; Excess via lymphatics

---

PART 2: SODIUM AND WATER BALANCE

Sodium Regulation (RAAS + ADH)

• Normal serum Na+ = 135-145 mEq/L
• Na+ = primary determinant of ECF volume and osmolality

RAAS Flowchart:

Low BP / Low Na+ / Sympathetic activation
→ Renin (from juxtaglomerular cells)
→ Angiotensinogen → Angiotensin I
→ Angiotensin II (via ACE in lungs)
→ Aldosterone (adrenal cortex) → Na+/H2O reabsorption
→ Vasoconstriction, ADH release, Thirst
→ Restored blood volume + pressure

ADH:

• Released from posterior pituitary when osmolality >290 mOsm/kg or volume drops
• Action: increases water reabsorption in collecting duct (aquaporins)

Dehydration

Diarrhea: Isotonic/hypotonic ECF depletion, loss of HCO3- → metabolic acidosis, loss of K+ → hypokalemia

Vomiting: Loss of HCl → metabolic alkalosis, volume depletion → RAAS activation → hypokalemia

Dehydration Pathogenesis Flowchart:

Fluid loss → ↓ ECF volume → ↓ BP + ↑ osmolality
→ Baroreceptors + RAAS + Osmoreceptors activated
→ ADH + Aldosterone + Thirst
→ Na+/H2O retention + Water intake
→ If adequate: restored; If inadequate: hypovolemic SHOCK

Severity:

Edema

4 Mechanisms:

1. ↑ Capillary Hydrostatic Pressure - CHF, venous obstruction, portal hypertension → pushes more fluid out
2. ↓ Oncotic Pressure - Cirrhosis (↓ albumin synthesis), Nephrotic syndrome (urinary albumin loss), Malnutrition/kwashiorkor → less pulling force
3. ↑ Capillary Permeability - Inflammation, burns, sepsis, anaphylaxis, ARDS → leaky walls
4. Lymphatic Obstruction - Tumor, post-mastectomy, filariasis → fluid not drained

Types:

• Pitting edema - CHF, renal disease
• Non-pitting edema - Lymphedema, myxedema
• Pulmonary edema - Left heart failure, ARDS (most dangerous)
• Cerebral edema - Trauma, hyponatremia → ↑ICP
• Ascites - Liver cirrhosis
• Anasarca - Generalized (CHF, nephrotic, malnutrition)

Hyponatremia (Na+ < 135 mEq/L)

• Brain cells swell (water shifts in)
• Causes: SIADH, dilution (excess water), Na+ loss (diuretics, diarrhea), edematous states (CHF, cirrhosis, nephrotic)
• Symptoms: nausea → confusion → seizures, coma
• Warning: Correct SLOWLY - rapid correction → Central Pontine Myelinolysis (irreversible brain damage)

Hypernatremia (Na+ > 145 mEq/L)

• Brain cells shrink → tearing of bridging veins → intracranial hemorrhage
• Causes: Diabetes insipidus, fever/sweating, inadequate water intake
• Central DI: no ADH produced; Nephrogenic DI: kidneys don't respond to ADH

---

PART 3: POTASSIUM BALANCE

K+ Overview

• Normal serum K+ = 3.5-5.0 mEq/L
• 98% intracellular - dominant intracellular cation
• K+ determines the resting membrane potential (RMP) of cells
• Small changes = major effects on cardiac rhythm and neuromuscular function → lethal dysrhythmias

Hypokalemia (K+ < 3.5 mEq/L)

• Pathophysiology: hyperpolarization → cells less excitable → slower repolarization
• EKG: Flat T waves → U waves → prolonged QT → Ventricular Fibrillation / Torsades de Pointes
• Also: muscle weakness, cramps, paralysis, ileus, polyuria, metabolic alkalosis

Hyperkalemia (K+ > 5.0 mEq/L)

• Pathophysiology: partial depolarization → initially excitable → then INEXCITABLE
• EKG Progression: Peaked T waves → prolonged PR → wide QRS → loss of P wave → sine wave → cardiac arrest
• Treatment: 1) Ca gluconate (membrane stabilization) → 2) Insulin + dextrose (shift K+ in) → 3) Dialysis (remove K+)

---

PART 4: CALCIUM AND MAGNESIUM BALANCE

Calcium Overview

• Normal total Ca2+ = 8.5-10.5 mg/dL; Ionized Ca2+ = 4.5-5.3 mg/dL
• 99% in bone and teeth; ~1% ECF
• Ionized (free) Ca2+ = physiologically active form
• In blood: 40% albumin-bound, 10% anion-bound, 50% ionized

3 Regulatory Hormones (Diagram):

PTH (PRIMARY Regulator):

• Released when Ca2+ ↓
• Bone: osteoclast activation → Ca2+ and PO4 released from bone
• Kidney: ↑ Ca2+ reabsorption, ↓ PO4 reabsorption, activates Vitamin D
• Net: ↑ Ca2+, ↓ Phosphate

Vitamin D (Calcitriol):

• Activated by PTH in kidney (1-alpha hydroxylase)
• Gut: ↑ Ca2+ and PO4 absorption (primary action)
• Net: ↑ both Ca2+ and Phosphate

Calcitonin:

• Released from thyroid C-cells when Ca2+ ↑
• Opposes PTH: inhibits osteoclasts, ↑ urinary Ca2+ excretion
• Net: ↓ Ca2+

Calcium-Phosphate Reciprocal Rule:

Hypocalcemia (Ca2+ < 8.5)

• Chvostek sign: tap facial nerve → facial twitching
• Trousseau sign: BP cuff inflated → carpal spasm

Hypercalcemia (Ca2+ > 10.5)

• Bones: bone pain, fractures
• Stones: kidney stones, polyuria
• Groans: constipation, nausea, vomiting
• Psychic Moans: confusion, depression, coma
• Cardiac: shortened QT, bradycardia

Magnesium

• Normal = 1.5-2.5 mEq/L; 60% in bone; 39% intracellular
• Cofactor for >300 enzymes; required for PTH secretion and action
• Hypomagnesemia: Alcoholism (most common), diuretics, malabsorption
  • Causes refractory hypokalemia (fix Mg first!) and hypocalcemia
  • Torsades de Pointes, tremors, seizures
• Hypermagnesemia: Renal failure, antacid abuse
  • Loss of DTRs (first sign) → respiratory depression → cardiac arrest
  • Treat with IV calcium gluconate

---

PART 5: ACID-BASE BALANCE

Fundamentals

• Normal blood pH = 7.35-7.45
• pH < 7.35 = Acidosis; pH > 7.45 = Alkalosis

Henderson-Hasselbalch:

pH = 6.1 + log [HCO3-] / (0.03 x pCO2)
Normal: HCO3- = 24, pCO2 = 40, Ratio = 20:1

• Lungs = rapid compensation (minutes)
• Kidneys = definitive regulation (hours to days)

Buffer Systems

1. Bicarbonate-Carbonic Acid (most important ECF buffer): CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-
2. Protein buffers (most important ICF buffer): hemoglobin, plasma proteins
3. Phosphate buffer: important in ICF and urine

Four Primary Disorders Summary:

Metabolic Acidosis (pH < 7.35, HCO3- < 22)

• Compensation: Kussmaul breathing (deep rapid), Winter's formula: pCO2 = 1.5 x [HCO3-] + 8 ± 2
• Effects: ACIDOSIS DEPRESSES CNS and membrane excitability → confusion → coma; hyperkalemia (K+ exits cells)

Metabolic Alkalosis (pH > 7.45, HCO3- > 26)

• Compensation: hypoventilation; Expected pCO2 = 0.7 x [HCO3-] + 21 ± 2
• Effects: ALKALOSIS INDUCES HYPEREXCITABILITY AND TETANY (↓ ionized Ca2+); hypokalemia

Respiratory Acidosis (pH < 7.35, pCO2 > 45)

• Compensation: Acute - HCO3- rises 1 per 10 ↑ pCO2; Chronic - HCO3- rises 3.5 per 10 ↑ pCO2
• Features: headache, confusion, CO2 narcosis, flushing, cyanosis

Respiratory Alkalosis (pH > 7.45, pCO2 < 35)

• Compensation: Acute - HCO3- falls 2 per 10 ↓ pCO2; Chronic - HCO3- falls 5 per 10 ↓ pCO2
• Features: light-headedness, perioral tingling, carpopedal spasm/tetany, palpitations

ABG Interpretation Steps:

1. pH → Acidosis or Alkalosis?
2. Match pCO2 or HCO3- to determine if respiratory or metabolic
3. Check for compensation (never fully normalizes pH)
4. If metabolic acidosis: calculate Anion Gap

---

TAKE-HOME MESSAGES

1. TBW = 60%: ICF 40% (2/3), ECF 20% (1/3)
2. Na+ = primary ECF cation; K+ = dominant ICF cation - maintained by Na+/K+/ATPase
3. Edema = ↑hydrostatic pressure OR ↓oncotic pressure OR ↑permeability OR lymphatic obstruction
4. Tonicity dictates cell volume: Hypotonic → swelling; Hypertonic → dehydration
5. K+ determines RMP - hypo/hyperkalemia → lethal dysrhythmias
6. Ca2+ and PO4 reciprocally regulated; PTH is the primary regulator
7. 20:1 ratio maintains pH - lungs (fast) + kidneys (definitive)
8. Acidosis depresses CNS; Alkalosis → hyperexcitability + tetany

---