Transcript Cl − + HCO 3

90 percent
of filtered
HCO3–
Ammoniogenesis
actively
synthesize
–
HCO3 in
addition
HPO (pK 6.8)
excretion in the urine is
another mechanism for H elimination
to insecreting
H is trapped
the urine as the acid
H2PO +
H.
Distal
Pretubular Cell
NH4+
HCO3-
1mMol/Kg/day
H+
GLUTAMINE
NH3
2–
4
+
H+
NH3
+
K+
GFR
–
4
HEPATIC HCO3– “PRODUCTION” AND CONSUMPTION
1.
2.
3.
4.
5.
6.
7.
The liver is the principal organ that clears lactic acid produced by
different tissues of the body
Each mole of lactic acid is accompanied by a mole of H+ .
Lactic acid taken up can be metabolized by two pathways; either
oxidation to CO2 , or gluconeogenesis to form glucose and glycogen.
Removal of free H+ during lactate metabolism in effect increases the
available HCO3– pool by diminishing its consumption.
Decreased ECF pH stimulates hepatic lactate uptake unless the liver
itself is ischemic or hypoxic.
Countering H+consumption during lactate metabolism is HCO3–
consumption during synthesis of urea from protein and amino acid
catabolism. Urea synthesis, which occurs only in the liver, can be
written empirically as
Each mole of urea synthesis consumes two moles of HCO3– .
Urea produced by the liver is excreted in the urine. A normal daily
excretionof 30g urea in the urine translates to the equivalent of 1,000
mmol of HCO3–
ANALYTIC TOOLS USED IN
ACID-BASE CHEMISTRY
• The clinical significance of acid-base perturbations
is determined by the underlying cause rather than
the serum concentration of hydrogen and hydroxyl
ions.
• The accuracy of acid-base measurements, however,
is not determined by the blood gas value alone,
which measures volatile acid and pH.
• Rather, measurement of each of the strong and
weak ions that influence water dissociation,
although cumbersome, is essential.
Carbon Dioxide-Bicarbonate
(Boston) Approach
Many physicians have incorrectly
assigned the increase in HCO3- as
compensation for raised PCO2 .
It is not.
First, the approach is not as simple as it seems,
- concentration
The
increased
HCO
3 to confusing maps or
requiring the clinician to refer
reflects
increased
total CO
the body.
2 in arithmetic.
to learn formulas
and perform
mental
- reflect its role as a
Alterations
in
HCO
Second, the system neither
3 explains nor accounts
buffer,
and abnormalities
weak acid.
for manyCO
of the
complex acid-base
2 by-product,
Base Deficit or Excess
(Copenhagen) Approach
• Whole blood buffer base (BB)
• The sum of the bicarbonate and the
nonvolatile buffer ions (essentially the serum
albumin, phosphate, and hemoglobin)
• Normally, BB = [Na+ ] + [K+ ] − [Cl− ].
• The major drawback of the use of buffer base
measurements is the potential for changes in
buffering capacity associated with alterations
in hemoglobin concentration.
Base Deficit or Excess
(Copenhagen) Approach
• In 1958,
Siggard-Anderson and colleagues developed a
simpler measure of metabolic acid-base
activity, the BDE (base deficit or excess).
• They defined the BDE as the amount of strong
acid or base required to return pH to 7.4,
assuming a PCO2 of 40 mm Hg and
temperature of 38°C.
• in the 1960s : (nomograms )
standardized base excess (SBE)
• SBE = 0.9287 × [ HCO3− − 24.4 + (pH − 7.4)]
Base Deficit or Excess
(Copenhagen) Approach
• These measures may miss the presence
of an acid-base disturbance entirely; for
example
a hypoalbuminemic (metabolic alkalosis),
critically ill patient with a lactic acidosis
may have a normal range pH,
bicarbonate, and BE. This may lead to
inappropriate therapy.
Anion Gap Approach
• The first and most widely used tool for investigating
metabolic acidosis is the anion gap (AG), developed
by Emmit and Narins in 1975
• This is based on the law of electrical neutrality
• Na+ + K+ - (Cl− + HCO3− ) = -10 to -12 mEq/L ???
• If the gap "widens" to, for example, -16 mEq/L, the
acidosis is caused by UMAs (lactate or ketones).
Anion Gap Approach
• what is or is not a normal gap?
• Most critically ill patients are hypoalbuminemic, and many are also
hypophosphatemic .
• Corrected anion gap:
Anion gap corrected (for albumin) =
calculated anion gap + 2.5 × (normal albumin [g/dL] − observed albumin [g/dL])
• The second weakness with this approach is the use of bicarbonate in
the equation.
• An alteration in [HCO3- ] concentration can occur for reasons
independent of metabolic disturbance, such as hyperventilation.
• The base deficit (BD) and AG frequently underestimate the extent
of the metabolic disturbance
Stewart-Fencl Approach
A more accurate reflection of
true acid-base status SIDe
SIDa
SID= [(Na+ + Mg2+Strong
+ Ca2+ + K+ ) − (Cl− + A− )] =
40Cations
to 44mEq/L
Strong
[Cl− ]corrected = [Cl− ]observed × ([Na+ ]normal/[Na+ ]observed)
Anions
The normal SIG
as 8 ± 2 mEq/L.
SIDa = ( [Na+ ] + [K+ ] + [Mg2+ ] + [Ca2+ ] ) − [Cl− ]
•SIDe = [HCO3− ] + (charge on albumin) +
(charge on inorganic phosphate [Pi]) (in mmol/L)
Stewart-Fencl Approach
• BDE = Standard BDE
• CBE = Calculated BDE
• BEG = BDE − CBE
• BEfw = Changes in free water = 0.3 × (Na − 140)
• BECl = Changes in chloride = 102 − (Cl − 140/Na)
• BEalb = Changes in albumin = 3.4 × (4.5 − albumin)
• CBE = BEfw + BECl + BEalb
Stewart-Fencl Approach
1.
Hyperchloremic acidemia:
[Cl− ]corrected > 112 mEq/L.
2.
Hypochloremic alkalemia:
[Cl− ] corrected =
[Cl− ] observed × ([Na+ ] normal / [Na+ ] observed)
[Cl− ]corrected < 100 mEq/L.
3.
Dilutional acidemia :
serum sodium < 136 mEq/L
4.
Contraction alkalemia :
serum sodium > 148 mEq/L
5.
Hyperphosphatemic acidemia :
[Pi] > 2.0 mmol/L
6.
Hypoalbuminemic alkalosis :
[alb] < 3.5 g/dL
•
•
•
•
•
•
pH
7.33
Na = 117
K=
= 3.9
Ca = 3.0
Mg = 1.4
Cl = 92
Pi = 0.6 mmol/L
P
CO2 = 30 mm Hg
albumin = 6.0 g/L
pH = 7.33
PCO2 = 30 mm Hg
HCO3 = 15
AG =
= 13
AGcorrected = 23
BE
-10
BE = -10
SID = 18
Clcorrected = 112
and UMAcorrectedHCO
= 18.3 = 15 , AG = 13
Non-AG metabolic acidosis
bicarbonate wasting, such as renal tubular acidosis or
gastrointestinal losses
The degree of respiratory alkalosis is appropriate for
the degree of acidosis (ΔBD = ΔPCO2 )
SID is reduced to 18 mEq/L : free water excess,
UMAs, and surprisingly, hyperchloremia
the alkalizing force at play: hypoalbuminemia? ( 0.6g/dL )
The corrected AG mirrors the change in SID, but this is
grossly underestimated by the BD
Na = 117
K = 3.9
Mg = 1.4
Cl = 92
albumin = 6.0 g/L
pH = 7.33
HCO3 = 15
AG = 13
BE = -10
SID = 18
and UMAcorrected = 18.
Ca = 3.0
Pi = 0.6 mmol/L
PCO2 = 30 mm Hg
AGcorrected = 23
Clcorrected = 112
• This patient has a
dilutional acidosis,
a hyperchloremic acidosis,
and a lactic acidosis!
ACID-BASE PROBLEMS IN
DIFFERENT CLINICAL SETTINGS
Step 1. Look at the pH.
• 7.35 to 7.5 = normal or
compensated acidosis
• >7.5 = alkalosis
• <7.35 = acidosis
ACID-BASE PROBLEMS IN DIFFERENT CLINICAL SETTINGS
• Step 2. Look for respiratory
component
(volatile acid = CO2 ).
• PCO2 = 35 to 45 (normal range)
• PCO2 < 35 mm Hg = respiratory alkalosis
or compensation for metabolic acidosis
(if so, BD > -5).
• PCO2 >45 = respiratory acidosis
acute if pH < 7.35;
chronic if pH in normal range and BE > 5
ACID-BASE PROBLEMS IN DIFFERENT CLINICAL SETTINGS
• Step 3. Look for a metabolic component
(i.e., buffer base use).
• BD is the amount of strong cation required to
bring pH back to 7.4, with PCO2 corrected at
40 mm Hg.
• BE is the amount of strong anion required to
bring pH back to 7.4, with PCO2 corrected at
40 mm Hg.
• BE -5 to +5 = normal range
• BE >5 = alkalosis
• BD > -5 = metabolic acidosis
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7
Acidosis, CO2 < 35 mm Hg, ± BD > -5 =
acute metabolic acidosis
Normal-range pH, CO2 < 35, BD > -5 =
acute metabolic acidosis plus compensation
Acidosis, PCO2 > 45, normal-range BDE =
acute respiratory acidosis
Normal-range pH, PCO2 > 45, BE > +5 =
prolonged respiratory acidosis
Alkalosis, PCO2 > 45, BE > +5 =
metabolic alkalosis
Alkalosis, PCO2 < 35, normal-range BDE =
acute respiratory alkalosis
If the acid-base picture does not conform to any of
these options, a mixed pattern exists.
Acid-Base Disturbances in Emergency Settings
• The common disturbances
are:
acute respiratory acidosis
acute respiratory alkalosis
acute metabolic acidosis
• Acute metabolic alkalosis is
unusual.
Acute respiratory acidosis
• Hypoventilation :
loss of respiratory drive
neuromuscular disorders
chest wall disorders
rapid, shallow breathing, which increases the fraction of
dead-space ventilation.
Acute respiratory alkalosis
• Hyperventilation
anxiety,
central respiratory stimulation (salicylate poisoning)
excessive artificial ventilation
• Acute respiratory alkalosis usually accompanies
acute metabolic acidosis
• Reduction in PCO2 from baseline (usually 40 mm Hg) is equal to the
magnitude of the BD.
•BEfw = Changes in free water = 0.3 × (Na − 140)
+ 2.4 = 0.3 × ( 148 – 140 )
•BEalb = Changes in albumin = 3.4 × (4.5 − albumin)
+8.5 = 3.4
× ( 4.5= –
2 )− (Cl − 140/Na)
•BECl = Changes
in chloride
102
-17 = 102 – ( 120 – 140/148 )
Stewart-Fencl Approach
• BEfw = Changes in free water = 0.3 × (Na − 140)
+ 2.4 = 0.3 × ( 148 – 140 )
• BECl = Changes in chloride = 102 − (Cl − 140/Na)
-17 = 102 – ( 120 – 140/148 )
• BEalb = Changes in albumin = 3.4 × (4.5 − albumin)
+8.5 = 3.4 × ( 4.5 – 2 )
• CBE = BEfw + BECl + BEalb
-6.1 = 2.4 + ( - 17 ) + 8.5
• BEG = BDE − CBE
-5 = -11 – ( -6 )