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Metabolic Alkalosis
Mazen Kherallah, MD, FCCP, FCCM, FACP
Michigan State University
Society of Critical Care Medicine
Metabolic Alkalosis
Definition
• Elevated HCO3• Decline in [H+] in the ECF
Metabolic Alkalosis
HCO3/ECF Volume
Causes of Metabolic Alkalosis
Causes associated with contracted ECF volume
• Low urine Cl:
– Loss of gastric secretions: vomiting, nasogastric
suction
– Remote use of diuretics
– Delivery of nonreabsorbable anion plus Na:
Carbenicilline
– Posthypercapnia
– Loss NaCl in GI: congenital Cl loss, villous adenoma
• Persistent high urine Cl:
– Bartter’s-like syndromes
– Current diuretic use
Causes of Metabolic Alkalosis
Causes associated with normal or expanded ECF volume
• Large reduction in GFR plus a source of HCO3:
– Alkali ingestion
• Enhanced mineralocorticoid activity:
– primary aldosteronism
– Secondary hyperaldosteronism: renal artery stenosis,
malignant hypertension, renin producing tumor, low
effective arterial blood volume with an alkali load
– Endogenous or exogenous mineralocorticoid,
licorice ingestion, ACTH secretion
Metabolic Alkalosis
• Extracellular elevation of HCO3– Absolute: by addition of HCO3- to the ECF
– Relative: by the loss of ECF volume
• Intracellular events:
– Hypokalemia: Kaliuresis
– Intracellular acidosis: replacement of K by H
-
Addition of HCO3 to the ECF
• With the constraints of electroneutrality,
there are only two ways to add a specific
anion HCO3- to a compartment:
– Loss of an anion such as Cl– Retention of a cation such as Na+
Addition of HCO3- to the ECF
Loss of Cl- Anion
Gain of HCO3- in Plasma
Vomiting or nasogastric suction
Cl- loss in urine
Addition of HCO3- to the ECF
Retention of NaHCO3
Gain of HCO3- in Plasma
• When Na is retained in the ECF, its volume
is expanded
• If GFR is normal this extra Na and
bicarbonate will be excreted via the kidney
• GFR should be low (permission of the
kidneys) to retain extra Na and HCO3
Mechanisms for Renal Retention
of HCO3-
Contraction of the ECF Volume
Increased [HCO3-]
• The ECF volume is contracted secondary to
removal of NaCl and water
• The [HCO3-] is increased and the content is
unchanged
• Same HCO3- are distributed in smaller
volume
• Metabolic alkalosis: contraction alkalosis
Contraction of the ECF Volume
Diuretic Ingestion
• Diuretic ingestion causes NaCl loss in the
urine and ECF volume contraction
• Increased production and excretion of NH4
consequent to hypokalemia, thus new
HCO3 formation
Causes Associated with ECF
Volume Contraction
1. Vomiting or Nasogastric Suction
• Loss of HCl
• Generation of HCO3
• Excretion of NaHCO3
in the urine
• ECF contraction
• Renin will increase
angiotensin II and
aldosterone
• Excretion of K:
kaliuresis
•
•
•
•
•
•
How many liters of emesis must be lost in
order to raise the [HCO3-] in plasma by 10
mmol/L in 70-kg adult?
Extracellular [HCO3-] is 25 mmol/L and intracellular
is 10 mmol/L
10 X 15= 150 mmol extracellular
3.5 X 30= 100 mmol intracellular
Total HCO3 added is 250
1 liter of gastric fluid contains 100 mmol of H+ and
100 mmol of Cl2.5 liters is needed to be lost before HCO3 is raised
to 35
2. Diuretics
• Diuretics blocks Na and Cl
channels
• More Na is delivered to DCT
• Na exchange with K under
the effect of aldosterone
• Kaliuresis and hypokalemia
ensues
• Depleted ECF and high
aldosterone leads to
hypokalemia
• Hypokalemia augments renal
ammoniagenesis
Ammoniagenesis
Ammoniagenesis
When K is high in the lumen, fewer NH4 is reabsorbed because of the
competition between NH4 and K.
With hypokalemia more NH4 is reabsorbed and then secreted as NH3
combining with H and raising the HCO3 in plasma
Intracellular Acidosis in Metabolic
Alkalosis associated with Hypokalemia
• The depletion of K leads to a shift of cation
Na and H into the cells
• This shift exacerbates the degree of HCO3
elevation in the ECF and cause intracellular
acidosis
• Hypokalemia must be corrected first
3. Nonreabsorbable Anions
• If a patient has a contracted ECF volume and takes
an Na salt with an anion that cannot be reabsorbed
by the kidney: Carbenicillin
• There is stimulus for Na reabsorption but it cannot
be reabsorbed.
• In CCD the action of aldosterone will lead to
hypokalemia
• Hypokalemia will cause more ammoniagenesis and
thus increased plasma HCO3 and metabolic
alkalosis
3. Nonreabsorbable Anions
• Cl in urine should be < 20
• Na in the urine should be high
• Na + K should be > Cl due to the presence
of unmeasured anion
4. Posthypercapnia
• During chronic hypoventilation and
hypercapnia, plasma HCO3 concentration is
increased.
• HCO3 is generated in the kidney and
excretion of NH4Cl ensues
• When hypercapnia resolves increased
HCO3 content will cause metabolic
alkalosis
5. Loss of NaCl via the GI tract
• Congenital chloridorrhea, villous adenoma
• Loss of Na and Cl in stool
• Similar to diuretic induced metabolic
alkalosis
• The urine always has Na and Cl
6. Bartter-like Syndromes
•
•
•
•
•
•
•
•
Hypokalemia
Renal Na and Cl wasting
Contracted ECF volume
Metabolic alkalosis
hypereninemia
Deficiency of Mg
Hypertrophy of justaglomerular apparatus
High rate of Ca excretion
6. Bartter-like Syndromes
• The pathophysiology can be considered as
having a loop diuretic acting 24 hour a day
• Defect in Na, K, 2 Cl electroneutral
cotransporter: NKCC in the Luminal membrane
of the thick ascending limb of Henle
• this causes delivery of Na and Cl to CCD and
thus K excretion
• NaCl wasting and a low ECF volume results in
high level of renin
Causes Associated with Normal
or Expanded ECF Volume
1. Hyperaldosteronism
• Aldosterone causes hypokalemia
• Hypokalemia enhances ammoniagenesis,
which enables renal new CO3 formation
• Hypokalemia causes an increased indirect
reabsorption of HCO3 via the rise in
proximal tubular intracellular H
• Hypokalemia reduces GFR and thereby
maintains the elevated blood HCO3
2. Alkali Loading
• Under usual circumstances, NaHCO3
loading leads to only a mild elevation in
plasma HCO3 because most of these HCO3
are excreted
• In the presence of Na depletion or in renal
failure, clinically important elevation of
plasma HCO3 occur with NaHCO3
administration
3. Magnesium Depletion
• Mg enhances the NKCC mechanism
• Depleted Mg results in higher Na and Cl
excretion and Hypokalemia with metabolic
alkalosis
4. Milk-Alkali Syndrome
• Ingestion of large amount of milk and
absorbable antacids: CaCO3
• Patient excrete large amount of Ca and
HCO3 in the urine
• Ca deposits more in alkaline urine
• Deposition of Ca leads to renal function
impairment
• Thus HCO3 increased in plasma
Metabolic Alkalosis
Is GFR very low
Yes
No
Alkali intake
Ion-exchange resins
milk alkali syndrome
Vomiting
Is ECF volume
contracted
Yes
No
Urine Cl
>20
<10
Diuretics
Bartter
Mg depletion
Loss of gastric
fluid
Diuretic
Rare causes
Waht is the
renin and
aldo level
Both low
Low renin
Hihg aldo
Both high
Exogenous
mineralcorticoids
Cushing's syndrome
Primary
hyperaldosteronism
RAS
Renin tumor
Malignant hypertension
Reabsorption of Na+ in CCD
Electroneutral
Na
Na
Electrogenic
Na
Cl Cl
Na
Na
Na
Na-K ATPase
K
K
K
CCD
Cl K
Cl
Cl
K
K
Case # 1
• Toby, a 26-year old dancer, complains of
weakness. She denies vomiting and the
intake of medications other than vitamins.
• Physical examination reveals a thin woman
who has a contracted ECF volume.
Plasma
Urine
Na
133
52
K
3.1
50
Cl
90
0
HCO3
32
-
pH
7.48
8
Questions????
• What acid-base disturbance is present?
• Why is the Na in urine not lower, given the
presence of ECF volume contraction?
• Why is Toby hypokalemic?
• What is the basis for the acid-base
disturbance?
Discussion of Case # 1
• Metabolic alkalosis with hypokalemia
• Cl is low in urine because of the ECF volume contraction
and reabsorption of NaCl
• Na is high in the urine because it is excreted with an anion
other than Cl
• The very high urine pH indicated that the other anion is
HCO3: bicarbonaturia
• To the degree that the filtered load of HCO3 exceeds the
tubular capacity to reabsorb it, HCO3 are excreted
• Hypokalemia secondary to high urine delivery to CCD and
high aldosterone secondary to contracted ECF volume
• Body shape disorder and induced vomiting
Case # 2
• Farrah, a beautiful person, is concerned about her
body image so she diets most of the time. Her food
intake is erratic and consists mainly of vegetables
and fruits; she consumes little meat or table salt.
She jogs 60 Km per week and is asymptomatic.
• When she volunteered for a clinical research
project, she was surprised to find that she was
hypokalemic. She denied vomiting and the use of
diuretics or laxatives. Her ECF is contracted
Plasma
Urine
Na
138
63
K
2.7
34
Cl
96
0
HCO3
30
0
pH
7.45
5.6
Creatinine
0.7
-
Osmolality
287
563
Metabolic Alkalosis
Is GFR very low
Yes
No
Alkali intake
Ion-exchange resins
milk alkali syndrome
Vomiting
Is ECF volume
contracted
Yes
Urine Cl
No
>20
<10
Diuretics
Bartter
Mg depletion
Loss of gastric
fluid
Diuretic
Rare causes
Waht is the
renin and
aldo level
Both low
Low renin
Hihg aldo
Both high
Exogenous
mineralcorticoids
Cushing's syndrome
Primary
hyperaldosteronism
RAS
Renin tumor
Malignant hypertension
Discussion of case # 2
• ECF volume contraction, metabolic alkalosis with
hypokalemia and high aldosterone level
• ECF volume contraction with 0 Cl in urine but high Na
• Positive urine net charge indicative of an anion other
than Cl is present
• Low pH and high osmolal gap indicates that the anion is
not HCO3 (bicarbonate is 0)
• Negative NaCl balance because of poor dietary intake
and nonrenal loss, she has an unusual organic anion
load from her diet
Case # 3
• Solly has episodes of abdominal pain and
profuse diarrhea for months. More recently
he has vomited on occasion and has
suffered from episodic tingling and
weakness. He took antacids to relieve his
abdominal pain, but their beneficial effect
was transitory.
• Each time his condition reverts to normal
without therapy
Plasma
Admission
4 hours later
pH
Not done
7.50
PaCO2
Not done
48
HCO3
62
48
K
3.1
4.0
Anion gap
15
13
Creatinine
2.3
Urine
volume
60 ml
Discussion of Case # 3
• Metabolic alkalosis with hypokalemia
• Bicarbonate gain of non-renal cause secondary
to gastric HCl secretion
• Most-likely HCl loss from GI
• Low rate of excretion of HCO3 due to
decreased GFR
• ECF volume is not contracted due to Low GFR
• HCl reabsorption led to improvement in
metabolic alkalosis
• Zollinger-Ellison syndrome
Case # 4
• Mr. Green is 42 year old and is a chronic
alcoholic. He was brought to the emergency
room, obviously intoxicated. He had been
lying in the park in a pool of vomitus. On
physical examination, he was unkempt and
incoherent. He had a markedly contracted
ECF volume, was febrile (39) and had
evidence of pneumonia.
Plasma
Na
130
H
30
K
2.9
pH
7.53
Cl
80
PaCO2
25
HCO3
20
PaO2
60
Creatinine
1.4
Albumin
38
Urea
12
Glucose
150
Ketones
Weakly +
Osmolality 320
Expected Responses to Primary Acid-Base Disorders:
Disorder
Response
Metabolic acidosis
Acute respiratory
acidosis
Drop the 7 and the decimal point from the pH
For every mmol/L fall in HCO3 from 25, Paco2 drops 1
mm Hg
Drop the 7 and the decimal point from the pH
For every mmol/L rise in HCO3 from 25, Paco2 should
rise 0.7 mm Hg
For every twofold increase in Paco2, the plasma HCO3
should increase by 2.5 mmol/L from 25
Chronic respiratory
acidosis
For every mm Hg increase in Paco2, the plasma HCO3
should increase by 0.3 mmol/L from 25
Acute respiratory
alkalosis
For every mm Hg fall in Paco2, the plasma H+ should fall
by 0.8 mmol/L from 40
Chronic respiratory
alkalosis
For every mm Hg in Paco2, the plasma HCO3 should fall
by 0.5 mmol/L from 25
Metabolic alkalosis
Discussion of Case # 4
• Metabolic acidosis with increased anion gap
most likely alcoholic ketoacidosis, and Llactic acidosis type B secondary to thiamin
deficiency
• Metabolic alkalosis with vomiting and
hypokalemia
• Respiratory alkalosis from pneumonia
Case # 5
• Emily is 73 year old, she enjoys toast with jam along
with her traditional cup of tea.
• On her annual checkup, her physician told her that
her blood pressure is elevated 170/95, and gave her
thiazide diuretic.
• She has not been feeling well since she took her
medicine, she feels weak, she becomes lightheaded
when she stands up, and she is less able to perform
at her high intellectual level, she drinks a lot of
water
• On P.E. blood pressure 150/90 and orthostatic of 15
mm Hg, her urine volume is 0.5 L per day
Plasma
Urine
Na
107
3
K
1.9
12
Cl
67
7
HCO3
30
0
pH
7.47
5.1
Urea
4.2
-
Glucose
108
0
Osmolality
220
405
Is This Bartter’s Syndrome
• 50 year old paraplegic male has a
neurogenic bladder as a result of MVA. He
developed a UTI and was treated with
gentamicin 80 mg q8h for 2 weeks.
• There was no special findings on physical
examination, his ECF is not low
• Hypokalemia did not improve with 200
mmol per day. Urine output 2-5 L per day
Plasma
(admission)
Plasma
(day 14)
Na
140
140
49
K
3.8
1.6
36
Cl
HCO3
105
26
91
38
82
0
pH
7.40
7.48
5.5
Creatinine
0.7
0.6
-
BUN
11
10
-
Mg
2.2
2.2
-
Volume
-
-
3
Urine
Driven by lumen positive charges
H2O
Na+
Na+
Ca++
Mg++
NKCC
Na+
2Cl- ROM K-1 +
K
K+
2 Na+
2 Cl-
K+
Na+ K +
ATP
Cl-
Ca receptors
also binds
cations like
gentamicin
Case # 7
• Alicia is a 47 year old with history of
Hypertension which is controlled with
diuretics.
• Presented with dizziness and contracted
ECF
Plasma
Urine
Na
138
36
K
2.7
61
Cl
99
57
HCO3
28
0
pH
7.46
5.9
Mg
1.0
4
Creatinine
1
-
Osmolality
287
563