TRIPASS XR تري باس

11

Volume Regulation

Sodium resides almost exclusively in the ECF; the amount of total body sodium,

therefore, determines the extracellular volume.

2,11 Because daily sodium intake varies

from 100 to 250 mEq, the body must rely on adjustments in urinary sodium excretion

to maintain the extracellular volume and tissue perfusion.

2,11 The ability of the kidney

to retain sodium is so remarkable that a person can survive with a daily sodium

intake of as low as 20 to 30 mEq.

The afferent sensors for the changes in the effective circulating volume are the

intrathoracic volume receptors, the baroreceptors in the carotid sinus and aortic arch,

and the afferent arteriole in the glomerulus.

11

When the effective circulating volume is decreased, both the renin–angiotensin–

aldosterone and the sympathetic nervous systems are activated.

2,11 Angiotensin type 2

(AT2

) and norepinephrine enhance sodium reabsorption at the proximal convoluted

tubule. In addition, aldosterone stimulates sodium reabsorption at the collecting

tubule. The decrease in effective arterial volume also stimulates ADH release, which

enhances water reabsorption at the collecting duct. Conversely, after a salt load, the

increases in atrial pressure and renal perfusion pressure suppress the production of

renin and, subsequently, AT 2 and aldosterone. The release of atrial natriuretic

peptide secondary to increased atrial filling pressure and intrarenal production of

urodilators increase urinary excretion of the excess sodium.

12,13

Although the kidney can excrete a 20-mL/kg water load in 4 hours, only 50% of the

excess sodium is excreted in the first day.

3 Sodium excretion continues to increase

until a new steady state is reached after 3 to 4 days, when intake equals output.

3,12

It

is important to recognize that osmoregulation and volume regulation occur

independently of each other.

2,3 The two homeostatic systems regulate different

parameters and possess different sensors and effectors. Both systems can be

activated simultaneously, however.

DISORDERS IN VOLUME REGULATION

Sodium Depletion

CASE 27-2

QUESTION 1: A.B., a 17-year-old girl, presented to the emergency department (ED) with complaints of

anorexia, nausea, vomiting, and generalized weakness for the past 3 days. She denied other medical problems

and had not used any medications. On examination, her supine blood pressure (BP) was 105/70 mm Hg, with a

pulse of 80 beats/minute. Her standing BP was 85/60 mm Hg with a pulse of 100 beats/minute, and she

complained of feeling dizzy when she stood up. Her mucous membranes were dry, but her skin turgor was

normal. The jugular vein was flat, and peripheral or sacral edema was not present. Laboratory blood tests

showed the following:

Serum Na, 134 mEq/L

K, 3.5 mEq/L

Chloride (Cl), 95 mEq/L

Total CO2

content, 35 mEq/L

BUN, 18 mg/dL

Creatinine, 0.8 mg/dL

Glucose, 70 mg/dL

Random urinary sodium was 40 mEq/L, potassium was 40 mEq/L, and chloride was less than 15 mEq/L. The

hemoglobin was 14 g/dL, and white cell and platelet counts were normal. Based on the clinical and laboratory

data in A.B., what is the most probable explanation for her presentation?

The signs and symptoms in A.B. are consistent with volume depletion. The loss of

gastric fluid owing to vomiting and decreased oral intake secondary to anorexia led

to moderate-to-severe volume depletion. She exhibits orthostatic changes in both her

BP (a drop in systolic BP of 20 mm Hg) and pulse (an increase of 20 beats/minute).

The dry mucous membranes, the flat jugular vein, and the absence of edema support

volume depletion as well, and dizziness on standing indicates extracellular volume

depletion.

14 Her hypochloremic metabolic alkalosis was probably initiated by loss of

acidic gastric contents through vomiting. Her volume depletion increased renal

bicarbonate reabsorption, perpetuating the metabolic alkalosis. The decreased renal

perfusion brought about by volume depletion enhanced proximal

p. 572

p. 573

tubular reabsorption of urea, resulting in an increased BUN to creatinine ratio

(prerenal azotemia). When renal perfusion is decreased and the renin–angiotensin–

aldosterone system is activated, the proximal reabsorption of sodium and chloride is

increased. A.B.’s urinary sodium is, therefore, less than 10 mEq/L.

15 Excretion of the

poorly permeable bicarbonate ions, however, results in obligatory urinary sodium

loss to maintain luminal electroneutrality. A.B.’s urinary sodium was therefore

elevated (40 mEq/L). In this situation, the urinary chloride remained low, and this is

a better index of volume status.

15 Both urinary sodium and chloride are elevated,

however, in patients using diuretics, in those undergoing osmotic diuresis, and in

those with underlying renal disease or hypoaldosteronism, even in the face of volume

depletion. Physical examination should therefore be conducted as part of the volume

status assessment. A.B.’s volume depletion increased the concentration of red blood

cells, which could explain her slightly elevated hemoglobin concentration of 14 g/dL.

CASE 27-2, QUESTION 2: How should A.B.’s volume depletion be managed?

The etiology of A.B.’s vomiting should be sought and the cause removed. Because

the patient is neither hypernatremic nor hyponatremic, normal saline should be

administered intravenously to replenish the extracellular volume and improve tissue

perfusion.

2,14

If the patient is hypernatremic (having a greater deficit of water than

solute), half-isotonic saline or dextrose solution, which contains more free water,

should be administered. In contrast, hyponatremic hypovolemic patients have a

greater deficit of solute than water; isotonic or hypertonic saline should then be

given. The amount of volume deficit is often difficult to ascertain. Because A.B. was

severely orthostatic, 1 or 2 L of fluid can be given over the course of 2 to 4 hours.

The subsequent rate of infusion will depend on A.B.’s response and the prevailing

symptoms. The clinician should monitor her body weight, skin turgor, supine and

upright BP, jugular venous pressure, urine output, and urine chloride concentration to

assess the adequacy of volume repletion. Because the treatment goal is to achieve a

positive fluid balance, the infusion rate should be 50 or 100 mL/hour in excess of the

sum of urine output, insensible losses, and other losses, such as emesis and diarrhea.

2

Sodium Excess

CASE 27-3

QUESTION 1: L.J., a 45-year-old man, presented to the clinic with complaints of swollen legs and puffy

eyelids. He also noticed that his urine had been foamy recently. On examination, his BP was 180/100 mm Hg

and his pulse was 80 beats/minute. Bilateral periorbital edema and 2+ bilateral pitting edema up to the thigh

were noted. On auscultation, his heart was normal and his lungs had bilateral crackles. His jugular venous

pressure was elevated at 10 cm H2O. Laboratory tests revealed the following:

Serum Na, 132 mEq/L

K, 3.8 mEq/L

Cl, 100 mEq/L

Bicarbonate, 26 mEq/L

BUN, 40 mg/dL

Creatinine, 2.5 mg/dL

Glucose, 120 mg/dL

Albumin, 2 g/dL

Serum cholesterol, 280 mg/dL,

Triglycerides, 300 mg/dL

The serum transaminases, alkaline phosphatase, and bilirubin were within normal limits. Urinalysis showed

the following:

Specific gravity, 1.015

pH, 7.0

Protein, >300 mg/dL

24-hour urinary protein excretion, 6 g

Creatinine clearance (CrCl), 40 mL/minute

Urinalysis also showed oval fat bodies and fatty casts. L.J. was taking no medications and he denied illicit

drug use. Hepatitis B serology and human immunodeficiency virus (HIV) antibody were negative. The

impression was anasarca (total body edema) secondary to nephrotic syndrome. What is nephrotic syndrome?

What could be the cause of L.J.’s sodium excess state?

Nephrotic syndrome is characterized by hypoalbuminemia, urine protein excretion

greater than 3.5 g/day, hyperlipidemia, lipiduria, and edema.

16,17 The heavy

proteinuria is a result of damage to the selective barrier of the glomerulus. The

causes of nephrotic syndrome are multiple and diverse.

16 The causes can be

idiopathic (primary glomerular disease) or secondary to chronic systemic diseases

(e.g., diabetes mellitus, amyloidosis, sickle cell anemia,

18

lupus), cancer (e.g.,

multiple myeloma, Hodgkin disease), infections (e.g., HIV,

19 hepatitis B, syphilis,

malaria), intravenous (IV) drug abuse, and medications (e.g., gold, penicillamine,

captopril, nonsteroidal anti-inflammatory drugs [NSAIDs]

20

).