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14
14 Metabolic Alkalosis
367
The Fluid, Electrolyte and Acid-Base Companion
HCO3– HCO3–
pH | pH |
CO2 CO2
HCO3– HCO3–
pH | pH |
CO2 CO2
368
S. Faubel and J. Topf 14 Metabolic Alkalosis
Generation Maintenance
HCO
3
HCO3
HC
O
3
HCO3
HCO3
1 5 HCO3
HCO
HCO3
2
3
6 HCO3
HC
O3
HC
O3
3
HCO3
7
3
4
O
H+
HC
O3
HC H+
H+
369
The Fluid, Electrolyte and Acid-Base Companion
130 109
4 28 TPN
++
Ca 3
Lactated Ringer’s contains Packed red blood cells con- Total parenteral nutrition
lactate, which is converted tain citrate, which is converted (TPN) contains acetate, which
into bicarbonate. into bicarbonate. is converted into bicarbonate.
370
S. Faubel and J. Topf 14 Metabolic Alkalosis
py
ruvate •
ruvate •
liver cells
all cells
py py
ruv
mitochondria mitochondria
acetyl acetyl
CoA CoA
a
a
Lactate production Lactate consumption
When mitochondrial function is impaired, the body When mitochondrial function is restored, lactate
relies on anaerobic glycolysis to produce ATP. This is converted back into pyruvate in the liver. The
+ +
reaction requires NAD which is produced by the production of pyruvate uses the lactate and H
conversion of pyruvate into lactic acid (lactate and created from the breakdown of pyruvate. The con-
H+), causing lactic acidosis. sumption of H+ reverses the acidosis.
371
The Fluid, Electrolyte and Acid-Base Companion
l a c t a t e– H+
lactate– H+
l a c t a t e– H+
H+ HCO3
HCO
3
va
+
– H
py
lac tate
losis.
pyru
pyruv
a te
372
S. Faubel and J. Topf 14 Metabolic Alkalosis
3
1
2
HC
3
O
HC
O3
3
HCO
HCO3
5
4 1 5
HCO HCO
HCO3
2
3 3
6 6
HC
O3
HC
HCO3
O3
7 3
HCO3
O3 Cl
7
HC
3
4
O
HC
O3
HCO3 HC
Before the loss of chlo- After the loss of fluid, the amount
ride-rich (bicarbonate- of bicarbonate does not increase
poor) fluid. but its concentration does.
Loss of fluid generates metabolic alkalosis when the fluid lost has a low
concentration of bicarbonate. This kind of fluid loss decreases plasma water
while the amount of bicarbonate remains the same. Thus, the bicarbonate
concentration increases. This is known as a contraction alkalosis.
Because all bodily fluids are electrically neutral (equal number of anions
and cations), fluids which contain a small amount of bicarbonate tend to be
rich in chloride. Fluid losses that are high in chloride and low in bicarbon-
ate which can generate metabolic alkalosis include:
• vomiting and nasogastric suctioning
• diuretic use (thiazide or loop)
• sweating (only in patients with cystic fibrosis)
Metabolic alkalosis caused by vomiting, nasogastric suctioning and diuretic use is gener-
ated by more than one factor. In these disorders, metabolic alkalosis is generated by con-
traction alkalosisand hydrogen ion loss (discussed on the following pages).
Bodily fluids that are rich in _______ tend to be low in bicarbonate. chloride
373
The Fluid, Electrolyte and Acid-Base Companion
H+ H+
H+
H+
H+
H+
H+
into two categories: extra-renal and renal. Extra-renal hydrogen loss is ei-
ther from the GI tract or a shift into cells. Regardless of the source, loss of
hydrogen ion generates metabolic alkalosis because for every hydrogen ion
lost, one bicarbonate is added to the plasma.
GI loss. The loss of gastric secretions by vomiting or nasogastric suction
generates metabolic alkalosis. The pH of gastric juice is 1.0, representing a
hydrogen concentration that is one million times the hydrogen concentra-
tion of blood. Of all the causes of metabolic alkalosis, vomiting can result in
the most dramatic rise in pH. Normal gastric physiology and the effects of
vomiting are described in detail on the following page.
Intracellular loss. Intracellular loss of hydrogen ion can occur in severe
hypokalemia. When plasma potassium is low, potassium is released from cells
in exchange for hydrogen. Refeeding carbohydrates after a fast can also gener-
ate metabolic alkalosis, in part due to the shift of hydrogen into cells.
The rare and the random:Two other causes of GI hydrogen loss which can generate metabolic
alkalosis include congenital chloride diarrhea and colonic villous adenoma.
These are rare disor-
ders characterized by diarrhea that is rich in chloride and hydrogen.
Although diarrhea normally
causes an acidosis, diarrhea in these disorders can cause metabolic alkalosis.
374
S. Faubel and J. Topf 14 Metabolic Alkalosis
375
The Fluid, Electrolyte and Acid-Base Companion
NE
H+
H+
W
For every hydrogen ion excreted, one
!
HCO3 HCO3 bicarbonate ion is resorbed. There-
fore, excess hydrogen excretion
NE
H+ causes excess bicarbonate resorption,
W
!
generating metabolic alkalosis.
HCO3
NE
+
H
W
!
H+
H+
Loss of hydrogen ion in the urine in excess of the daily acid load aaa
can generate metabolic ___________. alkalosis
376
S. Faubel and J. Topf 14 Metabolic Alkalosis
ATP
H+ H+ OH
HCO3
H+ AMP CO2
NE
H+ HCO3
W EW EW!
!
N
HCO3
H+ intercalated cell
!
N
Mineralocorticoids are hormones which act at the collecting tubules to
stimulate the resorption of sodium and the excretion of both hydrogen and
potassium. Aldosterone is the most important mineralocorticoid.
The effect of mineralocorticoids on hydrogen ion excretion is important in
the generation of metabolic alkalosis. Mineralocorticoids act at the H+-
ATPase pump of the intercalated cells to increase hydrogen secretion (bi-
carbonate production). In the disorders of excess mineralocorticoid activity,
excess hydrogen excretion increases the resorption of bicarbonate, generat-
ing metabolic alkalosis.
The disorders of excess mineralocorticoid activity are typically associated
with hypokalemia, hypertension and mild hypernatremia. There are four
important causes of mineralocorticoid excess:
• primary hyperaldosteronism
• Cushing’s syndrome
• congenital adrenal hyperplasia
• hyperreninism (renal artery stenosis)
Pseudohyperaldosteronism is a rare cause of excess mineralocorticoid activity
. It results
from the use of exogenous substances which induce mineralocorticoid activity
. Pseudohy-
peraldosteronism can be due tolicorice ingestion
, carbenoxoloneand chewing tobacco .
See Chapter 18, Hypokalemia, page 509.
377
The Fluid, Electrolyte and Acid-Base Companion
378
S. Faubel and J. Topf 14 Metabolic Alkalosis
principle cell
Loop and thiazide di-
uretics increase the Na+
delivery of sodium to Na+
the distal nephron.
Na+
Increased delivery of
sodium increases
the resorption of so-
dium. This increases ATP
the negative charge
in the tubule lumen.
HCO3
The negative charge in H+ H+ OH
NE NE
the tubular lumen en- HCO3
W
!
hances the secretion + CO2
H HCO3
of hydrogen (resorp-
W EW
AMP
!
tion of bicarbonate). +
H
N
intercalated cell
!
The use of loop and thiazide diuretics can generate metabolic alkalosis by
increasing the renal excretion of hydrogen.
Loop and thiazide diuretics inhibit sodium resorption in the loop of Henle
and the distal tubule, respectively. Since sodium resorption is inhibited at
these sites, the delivery of sodium to the distal nephron is increased. As
sodium delivery increases, the resorption of sodium also increases. This in-
creases the negative charge in the tubular lumen. The negatively charged
tubular lumen enhances the secretion of hydrogen by the intercalated cells.
Loop and thiazide diuretics __________ the distal delivery of so- increase
dium.
379
The Fluid, Electrolyte and Acid-Base Companion
C
C
C
C
C C
C C
C C
C C
Some patients with severe, chronic lung disease are unable to effectively
ventilate and, as a consequence, retain CO2. Chronic retention of carbon
dioxide causes chronic respiratory acidosis. To compensate for the low pH,
the kidney increases hydrogen excretion and retains bicarbonate. Bicarbon-
ate levels can rise above 40 mEq/L in chronic respiratory acidosis.
If a patient with chronic CO2 retention and respiratory acidosis becomes ill
(e.g., pneumonia), she may require intubation and mechanical ventilation. In
this situation, mechanical ventilation may be used improperly to rapidly lower
the CO2, while the bicarbonate concentration remains elevated.
The elevated bicarbonate, which was appropriate compensation for the in-
creased CO2, is inappropriate for the newly-lowered CO2. The appropriate re-
nal response in this setting is to stop excreting hydrogen (producing bicarbon-
ate). This response, however, takes days to occur. Therefore, hydrogen excre-
tion (bicarbonate production) continues, the pH rises and metabolic alkalosis is
generated.
Due to the ability to cause metabolic alkalosis, mechanical ventilation in
patients with chronic CO2 retention needs to be approached with care. In these
patients, the key to proper ventilation is to follow the pH. By maintaining a
normal pH, the appropriate PCO2 for the bicarbonate can be achieved.
Cl– Cl– H+ H+
AMP
When chloride is resorbed When little chloride is deliv- The negative charge in-
with sodium in the distal tu- ered to the distal tubule, so- creases the secretion of
bule, there is no change in the dium is resorbed without an hydrogen by the interca-
charge of the tubular fluid. anion, producing a negative lated cells.
charge in the tubular fluid.
381
The Fluid, Electrolyte and Acid-Base Companion
ATP
H+ H+ OH
HCO3
H+ AMP CO2
NE
+ HCO3
H
W EW EW!
!
N
HCO3
H+ intercalated cell
!
N
excess mineralocorticoid
activity
hypovolemia
HC
O3
O HCO
3
HC
O3
K+ HCO K+ HCO
HC
CO
– –
3 3
hypokalemia hypochloremia
Note that excess mineralocorticoid activity and volume depletion can both generate and
maintain metabolic alkalosis.
The factors which maintain metabolic alkalosis are _____ volume, low
_____ chloride, _____ potassium and excess mineralocorticoid activity. low; low
382
S. Faubel and J. Topf 14 Metabolic Alkalosis
ATP
H+ H+ OH
HCO3
H+ CO2
NE NE
AMP HCO3
W
! W!
H+
HCO3
+
H intercalated cell
NE NE
HCO3
W
!
W
!
Excess mineralocorticoid activity can maintain metabolic alkalosis by in-
creasing hydrogen secretion (bicarbonate production) through its action at
the H+-ATPase pump. Excess mineralocorticoid activity is either due to a
disorder of mineralocorticoid excess or to the physiologic secretion of aldos-
terone in response to volume depletion.
Mineralocorticoid excess. The important causes of excess mineralo-
corticoid activity are primary hyperaldosteronism, Cushing’s syndrome, con-
genital adrenal hyperplasia and hyperreninism (renal artery stenosis). In
all of these disorders, mineralocorticoid activity is inappropriately elevated
and serves to both generate and maintain metabolic alkalosis.
Hypovolemia with secondary hyperaldosteronism. Many of the dis-
orders of metabolic alkalosis are associated with hypovolemia which stimu-
lates the release of aldosterone. Increased aldosterone secretion is an appro-
priate response to volume depletion, but serves as a common maintenance
factor in metabolic alkalosis generated by other causes. Secondary hyperal-
dosteronism does not generate metabolic alkalosis.
383
The Fluid, Electrolyte and Acid-Base Companion
Na + Na +
HCO3
Na + Na +
Na + HCO3 Na +
HCO3
Although the majority of bicarbonate is resorbed in volume depletion and metabolic alkalo-
sis, some bicarbonateis excreted in the urine.This bicarbonate is accompanied by sodium
to maintain electroneutrality
. This causes the urine sodium to be higher than what would be
expected in volume depletion. As will be discussed later in this chapter
, the urine chloride is
a better indicator of volume status than the urine sodium in metabolic alkalosis
.
BUN
Na Cl + –
glucose
K+ HCO –
Cr
3
HC
O3
O
HCO
3
HC
O3
O3
HC
CO
Chloride deficiency is associated with _________, diuretic use and cys- vomiting
tic ________. fibrosis
385
The Fluid, Electrolyte and Acid-Base Companion
Electrolyte composition
of gastric secretions:
H+ ................ 25-100
Na+ ............... 40-160
Cl– ................ 200
K+ ................. 15
The loss of gastric fluid from vomiting results in the loss of water,
hydrogen ion, and chloride. Metabolic alkalosis is generated due to hy-
drogen ion loss (bicarbonate gain) and chloride-rich fluid loss (contrac-
tion alkalosis); see pages 375 and 373.
The maintenance of metabolic alkalosis in vomiting is due to all four
maintenance factors:
Hypovolemia is due to the direct loss of fluid from
the stomach. Vomiting can cause the loss of one to
two liters of fluid per day. The resulting hypovolemia
stimulates sodium resorption which obligates the re-
HCO3
HCO3
H+ HCO3
W W W
H +
CO2
!
HCO3
tion).
H+
intercalated cell
! !
Cl
Hypochloremia is due to the direct loss of chloride
– from gastric fluid. Gastric fluid has a high concen-
tration of chloride (up to 200 mEq/L).
K+
Hypokalemia is not due to the direct loss of potas-
sium from the stomach. Gastric fluid has a low con-
centration of potassium. Vomiting does, however, in-
crease the renal loss of potassium. This mechanism
is described in detail in Chapter 18, Hypokalemia.
386
S. Faubel and J. Topf 14 Metabolic Alkalosis
Saline-responsive Saline-resistant
Contraction alkalosis Intracellular hydrogen loss
Vomiting Profound hypokalemia
Nasogastric suctioning Refeeding carbohydrates after fasting
Diuretic use Renal hydrogen loss
Sweating (in CF patients only) Excess mineralocorticoid activity
Addition of bicarbonate • Primary hyperaldosteronism
Lactated Ringer’s (lactate) • Cushing's syndrome
Blood transfusions (citrate) • Congenital adrenal hyperplasia
TPN (acetate) • Hyperreninism
Bicarbonate treatment in acidosis Pseudohyperaldosteronism
GI hydrogen loss • Licorice ingestion
Vomiting • Carbenoxolone
Nasogastric suctioning • Chewing tobacco
Congenital chloride diarrhea Rare causes
Colonic villous adenoma Bartter’s syndrome
Renal hydrogen loss Hypercalcemia
Diuretic use Hypoparathyroidism (without hypercalcemia)
Correction of chronic hypercapnia Magnesium deficiency
Penicillin, carbenicillin, ticarcillin Milk-alkali syndrome
ate, contraction alkalosis and loss of hydrogen) and four types of mainte-
nance factors (hypovolemia, low chloride, low potassium and excess miner-
alocorticoid activity), all of the causes of metabolic alkalosis are divided into
just two categories: saline-responsive and saline-resistant. These categories
reflect whether or not the metabolic alkalosis can be corrected by 0.9% NaCl.
The saline-responsive causes of metabolic alkalosis are all associated
with hypovolemia, with or without chloride depletion. In these disorders,
the metabolic alkalosis can be corrected by the administration of saline,
regardless of which factor generated the metabolic alkalosis.
The saline-resistant causes of metabolic alkalosis include all of the dis-
orders of excess mineralocorticoid activity and a handful of other rare con-
ditions, listed above.
The many causes of metabolic alkalosis are categorized based on aaa
the ability to treat them with __________. saline
387
The Fluid, Electrolyte and Acid-Base Companion
Cl-
HCO3 HCO3
HCO3
HCO3 HCO3
+
H
Cl-
Cl- Cl-
H+
Cl-
HCO3
388
S. Faubel and J. Topf 14 Metabolic Alkalosis
HCO3
HCO3
NE
H+
H+
W
Addition of bicarbonate
!
H+
HCO3 HCO3
Lactated Ringer’s
NE
H+
W
+
!
H
Blood transfusions HCO3
1 5
NE
HCO H+
TPN
W
HCO3
2
3
!
H+
6 H+
HC
Bicarbonate
O3
HC
O3
3
in acidosis H+
HCO3
7
3
4
O
HC
O3
HC
389
The Fluid, Electrolyte and Acid-Base Companion
H+ H+
ATP H +
H+ H+ OH
HCO3
H+ AMP CO2
NE
+ HCO3
H
W EW EW!
!
N
HCO3
H+ intercalated cell
!
N
Hypertensive Normotensive
Excess mineralocorticoid activity Intracellular hydrogen loss Rare causes
Primary hyperaldosteronism Severe hypokalemia Bartter’s syndrome
Cushing’s syndrome Refeeding carbohydrates Hypercalcemia
Hyperreninism (renal artery stenosis) after fasting Hypoparathyroidism
Congenital adrenal hyperplasia Magnesium deficiency
Pseudohyperaldosteronism Milk-alkali syndrome
390
S. Faubel and J. Topf 14 Metabolic Alkalosis
For a more detailed review of the diagnosis of these disorders, please see Chapter 18,
Hypokalemia, beginning on page 502.
391
The Fluid, Electrolyte and Acid-Base Companion
– –
pH | HCO3 pH | HCO3
CO2 CO2
In metabolic alkalosis, the primary To compensate for the increased
change is an increase in bicarbonate. HCO3–, the PCO2 must increase.
392
S. Faubel and J. Topf 14 Metabolic Alkalosis
54
52
50
PCO2 (mmHg)
48 s
46 al osi
alk
44
bo lic
42
m eta
40 Normal
38
36
34
20 22 24 26 28 30 32 34 36 38 40 42 44 46
Bicarbonate (mEq/L)
If the PCO2 falls within the predicted range, then appropriate respiratory
compensation has occurred and metabolic alkalosis is the only acid-base
disorder present.
If the PCO2 is outside the expected range, then a second acid-base distur-
bance is present. When the PCO2 is less than expected, a respiratory alkalo-
sis is also present. When the PCO2 is greater than expected, a respiratory
acidosis is also present.
The expected PCO2 in metabolic alkalosis is not as precise as the expected response in
metabolic acidosis.A simpler rule of thumb for the expectedCOP2 is that the PCO2 should
increase 0.5 to 1.0 mmHg for every 1 mEq/L increase in bicarbonate from normal.
393
The Fluid, Electrolyte and Acid-Base Companion
–
Expected PCO2 = 0.7 [HCO3 ] + 20 ± 1.5
and
lower metabolic alkalosis
than
expected respiratory alkalosis
and
higher metabolic alkalosis
than
expected respiratory acidosis
394
S. Faubel and J. Topf 14 Metabolic Alkalosis
O O CH2
C C
CH2 O CH3 CH3
HO C CH3 O C
H CH3
vomiting ketoacidosis
metabolic alkalosis & respiratory alkalosis metabolic alkalosis & respiratory acidosis
H+
H+ Cl
Cl
H+
H+
Cl
C
Cl
C
C
C
C
C
C
C
vomiting pneumonia diuretic use COPD
395
The Fluid, Electrolyte and Acid-Base Companion
Summary!Metabolic alkalosis.
Metabolic alkalosis is one of the four primary acid-base disorders and is char-
acterized by a bicarbonate greater than 24 mEq/dL and a pH greater than 7.40.
After respiratory compensation, the PCO2 is greater than 40 mmHg.
metabolic acidosis metabolic alkalosis respiratory acidosis respiratory alkalosis
HCO –
HCO – HCO3– HCO3–
pH |
3
pH |
3 pH | pH |
CO2 CO2 CO2 CO2
396
S. Faubel and J. Topf 14 Metabolic Alkalosis
Summary!Metabolic alkalosis.
EXCESS MINERALOCORTICOID ACTIVITY – DETAILS
Na+ Cl–
K+ HCO
ATP
H+ H+ OH
–
3
HCO3
H+ AMP CO2
NE
+ HCO3
H
W EW EW!
!
N
HCO3
H+ intercalated cell
!
N
the overview page for the complete list of causes (page 387).
C
C –
–
pH | HCO pH | HCO3
C
3 C
C
CO2 C
C
CO2
C
397
The Fluid, Electrolyte and Acid-Base Companion
Summary!Clinical review.
Step 1. Recognize metabolic alkalosis.
K HCO3
Step 2. !Compensation.
Expected PCO2 = 0.7 [HCO3–] + 20±1.5
PC02 < expected metabolic alkalosis and respiratory alkalosis
PC02 = expected metabolic alkalosis only
PC02 > expected metabolic alkalosis and respiratory acidosis
saline-responsive saline-resistant
Saline-responsive metabolic alkalosis (urine chloride < 20 mEq/L)
! history
! K , Ca
+ ++
, Mg++ Low or normal renin High renin
398