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Topf 8 Hypernatremia
8
8 Hypernatremia
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The Fluid, Electrolyte and Acid-Base Companion
always equals
Hypernatremia Hyperosmolality
sodium > 145 mEq/L osmolality > 300 mmol/L
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S. Faubel and J. Topf 8 Hypernatremia
sometimes equals
Hyperosmolality Hypernatremia
osmolality > 300 mmol/L sodium > 145 mEq/L
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The Fluid, Electrolyte and Acid-Base Companion
Generation Maintenance
Factors which Factors which
predispose to hypernatremia interfere with thirst
or or
sense thirst
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S. Faubel and J. Topf 8 Hypernatremia
The plasma sodium concentration is measured in mEq/L, and like all con-
centrations, it is the ratio of solute (sodium) to water. Thus, a change in the
sodium concentration can occur by either a change in the amount of sodium
or a change in the amount of water. An increase in sodium concentration
occurs through an increase in the relative amount of sodium or a decrease
in the relative amount of water.
Although hypernatremia can be due to either a gain of sodium or a loss of
water, it is most often due to the loss of water.
Medical Greek: iatrogenic is a term used to denote a response to medical or surgical treat-
ment. It is usually used for unfavorable outcomes. (Iatro = physician.)
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The Fluid, Electrolyte and Acid-Base Companion
Na+
H2O
Na+ Na +
+
Na Na+
Na+ +
Na+ Na
Na+
Na+
+
Na
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S. Faubel and J. Topf 8 Hypernatremia
ATP ATP
Na+ 3 Na+ 2 K+
3
AMPNa+
H+ H+ OH
CO2
AMP
+
HCO3
K
NE
K+
W
!
Na+ Cl– Na+ Cl– Na+ Cl–
K+ HCO3– K+ HCO3– K+ HCO3–
170
114
The disorders of excess mineralocorticoid activity cause mild hypernatre-
mia. The important causes of excess mineralocorticoid activity are:
• primary hyperaldosteronism • hyperreninism
• congenital adrenal hyperplasia • Cushing’s syndrome
Mineralocorticoids act at the collecting tubules to stimulate the resorption of
sodium and the excretion of both potassium and hydrogen. The most important
mineralocorticoid is aldosterone. Excessive aldosterone levels occur in primary
hyperaldosteronism and hyperreninism.
Cortisol can also have mineralocorticoid activity. At normal levels, the min-
eralocorticoid effect of cortisol is minimal because it is rapidly metabolized. In
Cushing’s syndrome, however, cortisol levels are high enough to overcome its
enzymatic break down so that it has significant mineralocorticoid activity. In
congenital adrenal hyperplasia the biochemical intermediates of cortisol are
overproduced and have significant mineralocorticoid activity.
The disorders of excess mineralocorticoid activity are characterized by
hypertension, hypokalemia and metabolic alkalosis. Due to the phenom-
enon of pressure natriuresis, hypernatremia is usually mild. Pressure natri-
uresis is the spontaneous excretion of sodium which occurs with increased
blood pressure.
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The Fluid, Electrolyte and Acid-Base Companion
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S. Faubel and J. Topf 8 Hypernatremia
Renal Extra-renal
Water loss is divided into renal and _________ water loss. extra-renal
For hypernatremia to occur, the fluid lost must contain a _________ lower
sodium concentration than the plasma sodium concentration.
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The Fluid, Electrolyte and Acid-Base Companion
Na+
H2O
Insensible fluid loss is water that is lost from the skin and respiratory
tract by evaporation. This loss is “insensible” because it occurs without aware-
ness. Insensible water loss is normally 800 to 1,000 mL each day. Insensible
fluid loss is increased by fevers and burns. Respiratory fluid loss is increased
by hyperventilation and low humidity.
Sensible fluid loss from the skin refers to sweat. It is sensible because
individuals can sense this water loss. An important distinction between sen-
sible and insensible fluid losses from the skin is that sweat, unlike insen-
sible water loss, has a significant electrolyte composition. The sodium con-
centration of sweat is about 30 mEq/L. Since the purpose of perspiration is
the dissipation of heat, sensible loss is increased by activity and high tem-
peratures.
Infections, particularly urinary and respiratory, are commonly associ-
ated with hypernatremia. Infections predispose to hypernatremia by increas-
ing skin and respiratory water loss through fever, sweating and hyperventi-
lation.
Insensible water loss is best estimated per calorie metabolized, just like maintenance fluids.
(See page 44.) ave. mL/100cal range
insensible loss from the lungs............... 15 mL/100cal 10-60 mL/100cal
insensible loss from the skin
.................. 30 mL/100cal 20-100 mL/100cal
Insensible water loss is the __________ of water from the skin evaporation
and _____________ tract. respiratory
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S. Faubel and J. Topf 8 Hypernatremia
Cystic fibrosis (CF) is the most common le- Infertility in males is due to obstruction of
thal inherited disease affecting Caucasians. the vas deferens. Up to 98% of males with
About 5% of Caucasians carry the CF gene, CF are infertile. Because hormone function
resulting in one affected child for every is intact, these patients mature normally
2,000 live births. The incidence is much through puberty. Fertility in females is also
lower in African Americans (one in 17,000) reduced. However, with increasing survival
and people of East Asian descent (one in and better treatments, more women with
90,000). Over 300 genetic mutations have CF are successfully giving birth.
been identified which cause cystic fibrosis; Cystic fibrosis is diagnosed by measuring
the most common is the 6F508 which is the chloride content of sweat. Normal val-
present in 570% of Caucasian Americans ues are less than 30 mEq/L. In CF, it is al-
who have CF. ways above 60 mEq/L and usually above
Cystic fibrosis is characterized by three dis- 80 mEq/L. The test is done by stimulating
tinct clinical abnormalities: sweat production through use of electrodes
1. Elevated concentrations of sodium and or pilocarpine. Fifty to one hundred millili-
chloride in sweat. ters of sweat are collected for measurement.
The test is difficult to accurately perform
2. Increased viscosity of secretions from on children less than 2 months old.
mucous-secreting glands.
Other causes of elevated sweat chloride:
3. Increased susceptibility to chronic endo-
bronchial colonization by specific types adrenal insufficiency
of bacteria. glycogen storage disease type I
The morbidity and mortality associated fucosidosis
with cystic fibrosis is due to the increased hypothyroidism
viscosity of secretions which can cause ob- nephrogenic diabetes insipidus
struction and loss of function of the organ ectodermal dysplasia
involved. The primary areas affected are malnutrition
the lungs, GI tract and vas deferens. mucopolysaccharidosis
panhypopituitarism
The major pulmonary complications are
pneumonia, mucous plugging, bronchiecta- The use of the sweat chloride test has al-
sis, hemoptysis and pneumothorax. Respi- lowed the precise diagnosis of CF early in
ratory complications are the most frequent the disease when patients have only mini-
cause of death in CF. mal symptoms.
GI complications are due to the obstruction The sweat chloride test is a better screen-
of the pancreatic duct which causes pan- ing test than molecular techniques because
creatic insufficiency. Pancreatic insuffi- the numerous mutations make genetic di-
ciency is characterized by malabsorption, agnosis difficult. Probes are available for
malnutrition and fat-soluble vitamin defi- the twenty-five most common mutations,
ciencies. Pancreatic dysfunction can also allowing molecular confirmation in about
cause pancreatitis and diabetes mellitus. 85% of cases.
In infants, the increased viscosity of the
gastrointestinal secretions can cause meco-
nium ileus.
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The Fluid, Electrolyte and Acid-Base Companion
Fluid lost from either the upper GI tract or secreto- Fluid lost from osmotic di-
ry diarrhea does not predispose to hypernatremia. arrhea predisposes to hy-
pernatremia.
Fluid from the GI tract may be lost from the upper GI tract (stomach) or
the lower GI tract. Fluid lost from either of these sites may cause hypov-
olemia, but only certain kinds of fluid loss from the GI tract predispose to
hypernatremia.
Fluid loss from the stomach occurs with vomiting and nasogastric suc-
tion. The sodium concentration of gastric secretions is around 140 mEq/L,
similar to that of plasma. Because it does not cause the loss of water in
excess of sodium, gastric fluid loss does not predispose to hypernatremia.
Fluid loss from the lower GI tract is most commonly due to diarrhea. Of
the two major types of diarrhea, secretory and osmotic, only osmotic diar-
rhea predisposes to hypernatremia. Secretory and osmotic diarrhea are dis-
cussed further on the following pages.
Fluid loss from the upper GI tract can be due to _________ or vomiting
nasogastric ___________ and does not cause hypernatremia. suction
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The Fluid, Electrolyte and Acid-Base Companion
Etiology!Generation!Loss of water!Extra-renal!Secretory
diarrhea does not predispose to hypernatremia.
sodium + potas
lality sium
os mo
Infectious cholera causes severe secretory diarrhea and can cause the loss
Salmonella Yersinia
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S. Faubel and J. Topf 8 Hypernatremia
Etiology!Generation!Loss of water!Extra-renal!Osmotic
diarrhea does predispose to hypernatremia.
sodium + pota
lit+y
olaNa ssiu
m
os m
Na+
Na+
te
lu
so
te
so
te
lu lu
As always, things are not as simple as they may appear. Infectious diarrhea is typically
secretory, but often the mucosal surface is damaged, preventing the absorption of lactose
or other particles.This acquired malabsorption causes a secondary osmotic diarrhea in
addition to the primary secretory diarrhea.
Osmotically active solutes in the bowel draw _______ into the gut. water
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SICK INFANT
DIARRHEA
HYPERNATREMIA HYPERGLYCEMIA
HYPEROSMOLALITY
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S. Faubel and J. Topf 8 Hypernatremia
central
resorbed solutes
nonresorbed solutes
urea
glucose H
mannitol AD
nephrogenic
Although the loop and thiazide diuretics cause the loss of water in excess of sodium, they
are uncommon causes of hypernatremia. As explained in Chapter 6,Hyponatremia: The
Pathophysiology, these diuretics are more likely to cause hyponatremia.
There are two general causes of ________ fluid loss which predis- renal
pose to hypernatremia: osmotic diuresis and _______ insipidus. diabetes
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The Fluid, Electrolyte and Acid-Base Companion
Water flows into the medullary interstitium un- Less water flows into the medullary interstitium
til the concentration in the tubule equals the before the concentration in the tubule equals
concentration in the medullary interstitium. the concentration in the medullary interstitium.
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S. Faubel and J. Topf 8 Hypernatremia
glucosuria
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The Fluid, Electrolyte and Acid-Base Companion
so
lu
te
ouch! Ahhh!
Excess plasma urea may occur as a result of _______-rich tube feed- protein
ings, steroid-induced catabolism, GI bleeding or _______ failure. renal
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S. Faubel and J. Topf 8 Hypernatremia
H H
AD AD
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The Fluid, Electrolyte and Acid-Base Companion
Generation Maintenance
Gain of sodium
or
Loss of water
Although there are many factors which can generate hypernatremia, the
maintenance of hypernatremia is always due to the failure of the patient to
ingest sufficient quantities of water.
The factors which interfere with the appropriate ingestion of water are
reviewed on the following pages.
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S. Faubel and J. Topf 8 Hypernatremia
-or-
The addition of sodium or loss of The increase in osmolality caus- Thirst causes the ingestion of wa-
water causes a transient increase es the hypothalamus to stimulate ter which returns plasma osmo-
in plasma osmolality. thirst. lality to normal.
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Diagnosis!A complete explanation for hypernatremia requires
determining the cause of both generation and maintenance.
Question Question
What predisposed Why isn’t the patient
to hypernatremia? drinking water?
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S. Faubel and J. Topf 8 Hypernatremia
or
The two most important factors which help determine what generated
hypernatremia are the history and volume status. The conditions which led
to hypernatremia are usually apparent from the history. However, altered
mental status often accompanies hypernatremia (as either the cause or a
symptom), and a clear history may be unobtainable.
Hypervolemia points to excess sodium as the etiology. A hypervolemic
hypernatremic adult in the hospital is most likely the victim of iatrogenic
hypernatremia from hypertonic saline or bicarbonate infusion. An infant
with hypervolemic hypernatremia may be the victim of salt ingestion as
part of intentional child abuse.
Hypovolemia points to the loss of hypotonic fluid as the cause. History
and physical exam should attempt to uncover the source of the fluid loss.
The following pages elaborate on how to establish the cause of hypovolemic
hypernatremia.
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The Fluid, Electrolyte and Acid-Base Companion
H
AD
The best way to differentiate between extra-renal and renal water loss is
to look at a patient's urine. Renal loss of water causing hypernatremia is
either due to osmotic diuresis or diabetes insipidus.
In all three causes of water loss (extra-renal, osmotic diuresis and diabe-
tes insipidus), hypovolemia stimulates the renin-angiotensin II-aldosterone
system which causes the retention of sodium. Therefore, in all three cases,
the urine sodium concentration is low.
If the source of the fluid loss is extra-renal, then properly functioning
kidneys retain water and produce a small volume of highly concentrated
urine. In all causes of extra-renal fluid loss leading to hypernatremia, the
urine osmolality is increased and the urine volume is low.
In osmotic diuresis, the ADH axis is intact. Thus urine is able to be concen-
trated and the urine specific gravity is high (osmolality is high). In diabetes
insipidus, however, the ADH axis is disrupted and the ability to concentrate
urine is lost. This results in a dilute urine with a low specific gravity (low osmo-
lality). Differentiating central from nephrogenic diabetes insipidus requires the
water deprivation test. (See Chapter 9, Polyuria, Polydipsia.)
In extra-renal water losses, the urine sodium is _____ and the low
specific gravity is ____. high
In osmotic diuresis, the urine sodium is ____ and the specific low
gravity is ____. high
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S. Faubel and J. Topf 8 Hypernatremia
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ouch!
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S. Faubel and J. Topf 8 Hypernatremia
Na+
Na+
ouch! ahhh!
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The Fluid, Electrolyte and Acid-Base Companion
D5W
ouch!
D5W
D5W
D5W
Overaggressive treatment
INTRACELLULAR EXTRACELLULAR with D5W rapidly reduces INTRACELLULAR EXTRACELLULAR
COMPARTMENT COMPARTMENT the plasma osmolality. COMPARTMENT COMPARTMENT
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S. Faubel and J. Topf 8 Hypernatremia
.9%
or NaCl IV fluids .2%
NaCl
to D5W
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The Fluid, Electrolyte and Acid-Base Companion
50% 40%
WATER DEFICIT
IDEAL TOTAL BODY WATER CURRENT TOTAL BODY WATER
+ current
[Na ] TBW weight 50%; 40%
(kg)
60%
140
It must be emphasized that the calculation of fluid deficit is only an estimate based on
several assumptions. When treating a patient with hypernatremia, it is important to fre-
quently assess plasma sodium to assure that the rate of correction is proceeding as planned.
The water deficit is the ______ TBW minus the ________ TBW. ideal; current
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S. Faubel and J. Topf 8 Hypernatremia
kg
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ideal TBW
ideal sodium
Ideal TBW can then be solved for by dividing both sides of the equa-
tion by ideal Na+, 140 mEq/L.
What is the water deficit in a 6 kg infant 165 mEq/L × 3.6 L ÷ 140 mEq/L = 4 L
with a plasma Na+ of 165 mEq/L? water deficit = 4 L – 3.6 L = 0.4 L
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to
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The Fluid, Electrolyte and Acid-Base Companion
.9% or and
D5W D5W
NaCl
oral tap water diuretics
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S. Faubel and J. Topf 8 Hypernatremia
Treatment!Sample calculation.
= 62 Kg x 0.5
= 31 liters
= 38 liters – 31 liters
= 7 liters
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The Fluid, Electrolyte and Acid-Base Companion
In the previous example, free water was given over 64 hours to ac-
commodate the speed limit of 0.5 mEq/L. Many experts believe that
this can be done more quickly. An alternative treatment is to give half
of the deficit in the first 24 hours and remainder of the deficit over the
next one to two days.
Additionally, the equations on the previous page were explained in
order to provide a logical approach to the calculation of the fluid deficit.
If the logic is understood, the calculations can be derived without hav-
ing to look them up. The equation below is the commonly cited formula
to calculate the water deficit. Both approaches (the derivations described
and the formula below) will produce the correct answer for the water
deficit.
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S. Faubel and J. Topf 8 Hypernatremia
Summary!Hypernatremia.
Hypernatremia is defined as a sodium concentration over 145 mEq/L.
The development of hypernatremia is a two-step process: generation and
maintenance. Generation is due to the addition of sodium or the loss of wa-
ter. Maintenance is always due to inadequate ingestion of water.
GENERATION MAINTENANCE
CALCULATE THE WATER DEFICIT 0.5 mEq/L per hour for chron- 0.9% NaCl is given to hypov-
ic or asymptomatic hyper- olemic patients until euvolemia
[Na]
kg × 0.5 × 140 – 1 natremia. is restored; then, oral tap wa-
ter or D5W are given to specif-
In hypovolemia, the 0.5 is an es- 1.5 to 2.0 mEq/L per hour for ically correct hypernatremia.
timate of the % body water in acute, symptomatic hyper-
men. Use 0.4 for women and natremia. Diuretics and dextrose IV solu-
0.6 for infants. tions are used for hypervolem-
ic hypernatremia.
The subject of diabetes insipidus was introduced in this chapter. The next
chapter, Polydipsia, Polyuria, will cover the mechanism, pathophysiology
and diagnosis of diabetes insipidus.
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Summary!Clinical review.
Hypervolemic / euvolemic
! bicarbonate
Evaluate clinical situation and consider excess mineralocorticoid activity,
! potassium
mild hypernatremia
! blood pressure
metabolic alkalosis Excess
hypokalemia mineralocorticoid activity
hypertension
!plasma renin
!history and physical exam
If unremarkable, con-
sider clinical situation
!urine sodium
Hypovolemic
UNa > 20 mEq/L
+ Other diuretics
• loop
• thiazide
UNa < 20 mEq/L
+
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