Water, Electrolytes,
Acid-Base Balance
inadequate Na+ intake, excessive fluid loss from vom-
iting or diarrhea, diuretic abuse, and adrenal insufficiency.
Hyponatremia can decrease extracellular fluid volume,
diabetes, cirrhosis, nephrosis, and inappropriate ADH
results from loss of hypoosmotic fluid
(e.g., in bums, fevers, high environmental temperature,
exercise, kidney disease, diabetes insipidus) or increased
Na+ intake (e.g., administration of hypertonic NaCl solu-
tions, ingestion ofNaHC03).
The average K+ content of the human body is 40 mEq/kg.
K+ occurs mainly in intracellular space. It is required for
carbohydrate metabolism, and increased cellular uptake of
K+ occurs during glucose catabolism. K+ is widely dis-
tributed in plant and animal foods, the human requirement
being about 4 g/day. Insulin and catecholamines promote
a shift of K+ into the cells. Excess K+ is excreted in the
urine, a process regulated by aldosterone.
Plasma K+ plays a role in the irritability of excitable
tissue. A high concentration of plasma K+ leads to elec-
trocardiographic (ECG) abnormalities and possibly to car-
diac arrhythmia, which may be due to lowering of the
membrane potential. Low concentration of plasma K+ in-
creases the membrane potential, decreases irritability, and
produces other ECG abnormalities and muscle paralysis.
may occur in renal disease and adrenal
insufficiency owing to impairment of normal secretory
mechanisms. Metabolic acidosis, in particular diabetic aci-
dosis, and catabolism of cellular protein in starvation or
fever cause K+ release from cells. Treatment consists of
correction of the acidosis and promotion of cellular up-
take of K+ by administration of insulin, which enhances
glucose intake. In severe cases, ion exchange resins given
orally bind K+ in intestinal secretions.
may occur from loss of gastrointestinal
secretions (which contain significant amounts of K+) and
from excessive loss in the urine because of increased al-
dosterone secretion or diuretic therapy. Hypokalemia is
usually associated with alkalosis.
Chloride is the major extracellular anion. About 70% is
in the extracellular fluid. The average Cl~ content of the
human body is 35 mEq/kg. Chloride in food is almost com-
pletely absorbed. Plasma levels of Na+ and C l- in gen-
eral undergo parallel alterations. However, in metabolic
alkalosis, chloride concentration increases.
39.5 Acid-Base Balance
Normal blood pH is 7.35-7.45 (corresponding to 35-
45 nmol of H+ per liter). Values below 6.80 (160 nmol
of H+ per liter) or above 7.70 (20 nmol of H+per liter)
are seldom compatible with life. A large amount of acid
produced is a byproduct of metabolism. The lungs remove
14,000 mEq of CO
per day. From a diet that supplies 1 -2 g
of protein per kilogram per day, the kidneys remove
40-70 mEq of acid per day as sulfate (from oxidation
of sulfur-containing amino acids), phosphate (from phos-
pholipid, phosphoprotein, and nucleic acid catabolism),
and organic acids (e.g., lactic, /3-hydroxybutyric, and ace-
toacetic). These organic acids are produced by incomplete
oxidation of carbohydrate and fats, and in some conditions
(e.g., ketosis; see Chapter 18) considerable amounts may
be produced.
The most important extracellular buffer is the carbonic
acid-bicarbonate system:
+ H20 <=►
+ H+
As discussed in Chapter 1, at a blood pH of 7.4, the ratio
of [HCOj"] to [H
] is 20:1 and the system’s buffering
capacity can neutralize a large amount of acid. The sys-
tem is independently regulated by the kidneys, which con-
trol the plasma HCOj" level, and by the respiratory rate,
which regulates the Pco2- Protein and phosphate buffer
systems also operate in plasma and erythrocytes. Proteins
are especially important buffers in the intracellular fluid.
The hydroxyapatite of bone also acts as a buffer.
The medullary respiratory center senses and responds to
the pH of blood perfusing it and is the source of pulmonary
control. PCo
and perhaps Po
also influence the center,
together with nervous impulses from higher centers of the
brain. A decrease in pH results in an increased respiratory
rate and deeper breathing with a consequent increase in
the respiratory exchange of gases and lowering of Pco
which elevates the pH. Similarly, a decrease in respiratory
rate leads to accumulation of CO
, increase in Pco2, and
decrease in pH. Pulmonary responses to fluctuations in
blood pH are rapid, while renal compensatory mechanisms
are relatively slower.
The kidneys actively secrete H+ ions through three
1. Na+/H+ exchange,
2. Reclamation of bicarbonate, and
3. Production of ammonia and excretion of NH
The proximal tubule is responsible for reclamation
of most of the 4500 mEq of HCOj" filtered through
the glomeruli each day. H+ secreted into the tubules
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