Water, Electrolyte, Acid-Base, and Hemodynamic Disorders   107

c. In chronic renal failure (CRF), both concentration and dilution are lost. CRF: loss of
d. Syndrome of inappropriate ADH concentration and
(1) Epidemiology dilution
(a) SIADH accounts for ~50% of hyponatremia in hospitalized patients. SIADH: common cause
(b) Ectopic production of ADH is the most common cause of SIADH. of hyponatremia in
• Small cell carcinoma of the lung is the most common neoplasm ectopically hospitalized patient
producing ADH.
(c) Drugs that enhance ADH effect also produce SIADH and include: SIADH: MCC small cell
• Chlorpropamide, cyclophosphamide, vincristine, vinblastine, amitriptyline, carcinoma of lung
haloperidol, phenothiazines, and narcotics
(d) Other causes—hypothyroidism/hypocortisolism (thyroxine/cortisol normally SIADH: always
inhibit ADH) concentrating never
(2) Pathophysiology of electrolyte abnormalities diluting
(a) Urine is always being concentrated, never diluted, because ADH is always
present. SIADH: UOsm greater
• As expected, UOsm is greater than POsm. than POsm
(b) A hypotonic gain of water is producing a dilutional hyponatremia
SIADH: serum Na+
(TBNa+/↑↑TBW) and an increase PV. <120 mEq/L;
• Serum Na+ <120 mEq/L is diagnostic of SIADH TBNa+/↑↑TBW
(c) An increase in PV increases the peritubular capillary hydrostatic pressure (PH).
• Because PH is greater than PO, there is decreased proximal tubular cell UOsm and random
reabsorption of Na+ (refer to Box 5-1). UNa+ increased in
• Random urine Na+ >40 mEq/L is characteristic of SIADH. SIADH
(3) Clinical findings
• Mental status abnormalities, seizures, and coma commonly occur, because of
cerebral edema (H2O movement into ICF compartment).
(4) Treatment
• Mild SIADH is treated by restricting water. Rx SIADH: restrict water

Demeclocycline is often used when a patient has a small cell carcinoma of the lung. The drug
Demeclocycline: inhibits
inhibits the effect of ADH on the collecting tubules (acquired NDI), causing loss of fH2O in the ADH; produces NDI
urine. It is unnecessary to restrict water while the patient is taking the drug.

F. Potassium (K+) disorders

1. Functions of potassium include:
Hypokalemia inhibits
a. Regulation of neuromuscular excitability and muscle contraction insulin secretion
b. Regulation of insulin secretion
(1) Hypokalemia inhibits insulin secretion. Hyperkalemia stimulates
(2) Hyperkalemia stimulates insulin secretion. insulin secretion
2. Control of potassium
a. Aldosterone Aldosterone has primary
control of K+
(1) Aldosterone increases K+ excretion in Na+-K+ epithelial channels (see Fig. 5-7A).
(2) Aldosterone increases K+ reabsorption of K+ in H+/K+-ATPase pump (see Fig. 5-8). Alkalosis causes K+ to
b. Arterial pH move into cells;
(1) Alkalosis causes H+ to move out of cells and K+ into cells (Fig. 5-9A). potential for
• Potential for developing hypokalemia hypokalemia

Cell Cell

H+ H+ H+ H+
K+ K+ K+ K+

A Alkalosis B Acidosis
5-9:  Potassium (K+) shifts related to alkalosis (A) and acidosis (B). Note that in alkalosis, when the H+ ions are
decreased, H+ ions are available in cells for exchange with K+ to balance the charges. This may result in hypoka-
lemia. Similarly, in acidosis, when H+ ions are increased, cells can buffer the H+ ions in exchange for K+. This may
result in hyperkalemia. See the text for a full discussion of other factors that affect potassium levels.
 108   Rapid Review Pathology
TABLE 5-3  Causes of Hypokalemia
PATHOGENESIS
Decreased intake
Transcellular shift (intracellular)
Gastrointestinal loss
Renal loss
CAUSES
Occurs in elderly patients and those with eating disorders
Alkalosis (intracellular shift of K+): vomiting, loop/thiazide diuretics,
hyperventilation (respiratory alkalosis)
Drugs enhancing the Na+/K+-ATPase pump: insulin, β2-agonists (e.g., albuterol)
Diarrhea (~30 mEq/L in stool)
Laxatives
Vomiting (~5 mEq/L in gastric juice)
Loop and thiazide diuretics (most common cause): excessive exchange of Na+ for
K+ in late distal and collecting tubules
Osmotic diuresis: glucosuria
Mineralocorticoid excess: primary aldosteronism, 11-hydroxylase deficiency,
Cushing syndrome, glycyrrhizic acid (licorice, chewing tobacco), secondary
aldosteronism (cirrhosis, congestive heart failure, nephrotic syndrome;
decreased cardiac output decreases blood flow and activates renin-angiotensin-
aldosterone system)

5-10:  Electrocardiogram showing hypokalemia. A posi-

tive wave after the T wave is called a U wave (arrow).
U waves are a sign of hypokalemia. (From Goldman L, V2
Schafer AI: Cecil’s Medicine, 24th ed, Philadelphia, Saunders
Elsevier, 2012, p 737, Fig. 119-2A.)

Acidosis causes K+ to
move out of cells; (2) Acidosis causes H+ to move into cells (for buffering) and K+ out of cells
potential for (see Fig. 5-9B).
hyperkalemia • Potential for developing hyperkalemia
(3) Insulin and β2-agonists (e.g., albuterol) enhance Na+/K+-ATPase pump → K+ shift
Insulin, β2-agonists into cells → potential for hypokalemia.
enhance Na+/K+-ATPase (4) Digitalis, β-blockers, and succinylcholine inhibit Na+/K+-ATPase pump → K+ shift
pump: K+ moves into
cell; hypokalemia
out of cells → potential for hyperkalemia.
3. Hypokalemia (serum K+ <3.5 mEq/L)
Digitalis, β-blockers, a. Causes (Table 5-3)
succinylcholine inhibit b. Clinical and laboratory findings
Na+/K+-ATPase pump: K+ (1) Muscle weakness and fatigue are the most common complaints.
moves out of cell; • Muscle weakness is due to changes in intracellular/extracellular K+ membrane
hyperkalemia
potential.
Loop/thiazide diuretics: (2) Electrocardiogram (ECG) shows U waves (Fig. 5-10).
MCC hypokalemia (3) Polyuria
• In severe hypokalemia, collecting tubule cells become distended with fluid
Hypokalemia: muscle (vacuolar nephropathy), rendering them refractory to ADH (i.e., NDI).
weakness; ECG shows U (4) Rhabdomyolysis
wave • Hypokalemia inhibits insulin → ↓muscle glycogenesis → rhabdomyolysis (rupture
Hypokalemia: polyuria; of muscle) due to lack of ATP
NDI due to vacuolar c. Treatment
nephropathy (1) Oral/parenteral replacement of potassium
(2) ACE inhibitors (inhibit aldosterone, which reduces renal K+ losses)
Hypokalemia: (3) Potassium-sparing diuretics, angiotensin II receptor blockers
rhabdomyolysis 4. Hyperkalemia (serum K+ >5 mEq/L)
Hyperkalemia: ECG a. Causes (Table 5-4)
shows peaked T waves; b. Clinical findings
heart can stop in (1) Ventricular arrhythmias
diastole • Severe hyperkalemia (e.g., 7−8 mEq/L) causes the heart to stop in diastole.

TABLE 5-4  Causes of Hyperkalemia
PATHOGENESIS
Tissue breakdown
Increased intake
Transcellular shift (extracellular)
Decreased renal excretion
RTA, Renal tubular acidosis.
    Water, Electrolyte, Acid-Base, and Hemodynamic Disorders   109
CAUSES
Pseudohyperkalemia (e.g., hemolysis of RBCs due to traumatic venipuncture,
thrombocytosis, leukocytosis)
Rhabdomyolysis (rupture of muscle)
Increased intake of salt substitute
Infusion of old blood
K+-containing antibiotics
Acidosis
Drugs inhibiting the Na+/K+-ATPase pump: β-blocker (e.g., propranolol),
digitalis toxicity, succinylcholine
Renal disease: renal failure (most common cause), interstitial nephritis
(legionnaires disease, lead poisoning, sickle cell nephropathy, analgesic
nephropathy, obstructive uropathy)
Mineralocorticoid deficiency: Addison disease, 21-hydroxylase deficiency,
hyporeninemic hypoaldosteronism (destruction of juxtaglomerular
apparatus; type IV RTA)
Drugs: spironolactone (inhibits aldosterone); triamterene, amiloride (inhibit Na+
channels)

LEAD V3 5-11:  Electrocardiogram (lead V3) showing hyperkale-

mia. Arrows show peaked T waves, which are a sign of
hyperkalemia. (From Goldman L, Schafer AI: Cecil’s Medi-
cine, 24th ed, Philadelphia, Saunders Elsevier, 2012, p 738,
Fig. 119-3A.)

(2) ECG shows peaked T waves (Fig. 5-11).

• Due to accelerated repolarization of cardiac muscle
(3) Muscle weakness and depressed/absent deep tendon reflexes
• Hyperkalemia partially depolarizes the cell membrane, which interferes with
membrane excitability.
c. Treatment
(1) Low-potassium diet
(2) β-Adrenergic agonists (shifts K+ into cells) Calcium gluconate
(3) Calcium gluconate (cardioprotective by stabilizing cardiac cell membranes against cardioprotective in
depolarization) hyperkalemia
(4) Intravenous insulin with glucose (shifts K+ into cells), loop diuretics (lose K+ in
urine), cation exchange resins (exchange Na+ for K+ in colon) No compensation:
II. Acid-Base Disorders expected compensation
remains in normal range

Compensation refers to respiratory and renal mechanisms that bring the arterial pH close to but Partial compensation:
expected compensation
not into the normal pH range (7.35−7.45). In primary respiratory acidosis and alkalosis,
outside normal range;
compensation is metabolic alkalosis and metabolic acidosis, respectively. In primary metabolic pH outside normal
acidosis and alkalosis, compensation is respiratory alkalosis and respiratory acidosis, respectively. range
When the expected compensation remains in the normal range, an uncompensated disorder is
present. If compensation moves outside the normal range but does not bring pH into the normal Full compensation:
range, a partially compensated disorder is present. When compensation brings the pH into the compensation brings pH
normal range, full compensation is present, which rarely occurs with the exception of chronic into normal range;
respiratory alkalosis, particularly at high altitude. The pH defines the primary acid-base disorder. rarely occurs
For example, if there is a metabolic acidosis (↓HCO3−), a respiratory alkalosis (↓PaCO2), and an
acid pH (↓pH), the primary disorder is metabolic acidosis, and respiratory alkalosis is pH defines the primary
compensation. disorder versus the
compensation