Diuretics Table 511 XI Integrative Examples

A. Hypoaldosteronism

1. Case study

- A woman has a history of weakness, weight loss, orthostatic hypotension, increased pulse rate, and increased skin pigmentation. She has decreased serum [Na*], decreased serum osmolarity, increased serum [K*], and arterial blood gases consistent with metabolic acidosis.

2. Explanation of hypoaldosteronism a. The lack of aldosterone has three direct effects on the kidney: decreased Na* reabsorption, decreased K* secretion, and decreased H' secretion. As a result, there is ECF volume contraction (caused by decreased Na" reabsorption), hyperkalemia (caused by decreased K* secretion), and metabolic acidosis (caused by decreased H' secretion).

b. The ECF volume contraction is responsible for this woman's orthostatic hypotension. The decreased arterial pressure produces an increased pulse rate via the baroreceptor mechanism.

Table 5-11. Effects of Diuretics on the Nephron

Class of Diuretic

Carbonic anhydrase inhibitors (acetazolamide)

Loop diuretics (furosemide, ethacrynic acid, bumetanide)

Site of Action


Proximal tubule

Thick ascending limb of the loop of Henle

Thiazide diuretics (chlorothiazide, hydrochlorothiazide)

Early distal tubule (cortical diluting segment)

K+-sparing diuretics (spironolactone, triamterene, amiloride)

Late distal tubule and collecting duct

Inhibition of carbonic anhydrase

Inhibition of Na+-K+-2C1" cotransport

Inhibition of NaCl reabsorption

Inhibition of Na+ reabsorption Inhibition of K+ secretion (Note: spironolactone is an aldosterone antagonist; the others act directly)

Mayor Effects

î HCO3" excretion

T NaCl excretion T K+ excretion (because of T distal tubule flow rate) T Ca2+ excretion (treat hypercalcemia) -I ability to concentrate urine (because of 4-corticopapillary gradient) I ability to dilute urine (because of inhibition of diluting segment)

T NaCl excretion T K+ excretion (because of t distal tubule flow rate) •l Ca2+ excretion (opposite effect of other diuretics) I ability to dilute urine (because of inhibition of cortical diluting segment) No effect on ability to concentrate urine

T Na+ excretion (small effect)

■I K+ excretion ■I H* excretion c. ECF volume contraction also stimulates ADH secretion from the posterior pituitary via volume receptors. ADH causes increased water reabsorption from the collecting ducts, which results in decreased serum [Na+] (hyponatremia) and decreased serum osmolarity. Thus, ADH released by a volume mechanism is "inappropriate" for the serum osmolarity in this case.

d. Hyperpigmentation is caused by adrenal insufficiency. Decreased levels of Cortisol produce increased secretion of adrenocorticotropic hormone (ACTH) by negative feedback. ACTH has pigmenting effects similar to those of melanocyte-stimulating hormone.

B. Vomiting

1. Case study

- A man is admitted to the hospital for evaluation of severe epigastric pain. He has had persistent nausea and vomiting for 4 days. Upper gastrointestinal (GI) endoscopy shows a pyloric ulcer with partial gastric outlet obstruction. He has orthostatic hypotension, decreased serum [K+], decreased serum [CI-], arterial blood gases consistent with metabolic alkalosis, and decreased ventilation rate.

2. Responses to vomiting (Figure 5-23)

a. Loss of H+ from the stomach by vomiting causes increased blood [HC03~] and metabolic alkalosis. Because CI" is lost from the stomach along with H+, hypochloremia and ECF volume contraction occur.

b. The decreased ventilation rate is the respiratory compensation for metabolic alkalosis.

c. ECF volume contraction is associated with decreased blood volume and decreased renal perfusion pressure. As a result, renin secretion is increased, production of angiotensin II is increased, and secretion of aldosterone is increased. Thus, the ECF volume contraction worsens the metabolic alkalosis because angiotensin II increases H CO,, reab-sorption in the proximal tubule (contraction alkalosis).

d. The increased levels of aldosterone (secondary to ECF volume contraction) cause increased distal K+ secretion and hypokalemia. Increased aldosterone also causes increased distal H+ secretion, further worsening the metabolic alkalosis.

Vomiting i

Loss of gastric HCI

Loss of fixed H+

ECF volume contraction

I Renal perfusion pressure

t Aldosterone

t Angiotensin II

t Na+-H+ exchange t HCO3- reabsorption t H+ secretion T K+ secretion

Metabolic alkalosis (generation)

Metabolic alkalosis (maintenance)

Figure 5-23. Metabolic alkalosis caused by vomiting. ECF = extracellular fluid.

e. Treatment consists of NaCl infusion to correct ECF volume contraction (which is maintaining the metabolic alkalosis and causing hypokalemia) and administration of K+ to replace K+ lost in the urine.

C. Diarrhea

1. Case study

- A man returns from a trip abroad with "traveler's diarrhea." He has weakness, weight loss, orthostatic hypotension, increased pulse rate, increased breathing rate, pale skin, a serum [Na+] of 132 mEq/L, a serum [CI-] of 111 mEq/L, and a serum [K+] of 2.3 mEq/L. His arterial blood gases are: pH, 7.25; Pco2, 24 mm Hg; HC03", 10.2 mEq/L.

2. Explanation of responses to diarrhea a. Loss of HC03" from the GI tract causes a decrease in the blood [HC03~] and, according to the Henderson-Hasselbalch equation, a decrease in blood pH. Thus, this man has metabolic acidosis.

b. To maintain electroneutrality, the HC03~ lost from the body is replaced by Cl", a measured anion; thus, there is a normal anion gap. The serum anion gap = [Na+] - ([CI"] + [HCOg-]) = 132 - (111 + 10.2) = 10.8 mEq/L.

c. The increased breathing rate (hyperventilation) is the respiratory compensation for metabolic acidosis.

d. As a result of his diarrhea, this man has ECF volume contraction, which leads to decreases in blood volume and arterial pressure. The decrease in arterial pressure activates the baroreceptor reflex, resulting in increased sympathetic outflow to the heart and blood vessels. The increased pulse rate is a consequence of increased sympathetic activity in the sinoatrial (SA) node, and the pale skin is the result of cutaneous vasoconstriction.

e. ECF volume contraction also activates the renin-angiotensin-aldosterone system. Increased levels of aldosterone lead to increased distal K+ secretion and hypokalemia. Loss of K+ in diarrhea fluid also contributes to hypokalemia.

f. Treatment consists of replacing all fluid and electrolytes lost in diarrhea fluid and urine, including Na+, HC03~, and K+.

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