ACIDOSIS METABOLICA

Dr Enrique Alvarez L. Nefrólogo Infantil. CHSBA

Objetivos.
¨  Interpretar adecuadamente una gasometría.
¨  Identificar trastornos ácido-bases simples y

mixtos.
¨  Identificar causas y tratamientos de los

trastornos ácido-bases.
¨  Comprender los fundamentos fisiológicos del
equilibrio ácido-base, especialmente en la
acidosis metabólica.
 (Table 2). Metabolic disorders are expressed above the average normal value of 4.5 g/dl, respectively.
ry changes in plasma [HCO! 3 ], whereas respiratory Changes in blood pH elicit small, directional changes in the
are expressed as primary changes in PaCO2. Each anionic charge of plasma albumin and thus the AG, but these
change in either plasma [HCO! 3 ] or PaCO2 elicits in changes are ignored in clinical practice.28,29 The anionic
ondary response in the other variable that tends to charge of plasma albumin decreases by only 1.5 mEq/l when
review
the change in acidity.1,11 These secondary blood pH decreases fromHJ7.40 Adrogué et al.: Assessing
to 7.10.30 acid–base disorders

, otherwise referred to as compensatory, have been

ed in animals and humans.14–24 We discourage use Attributes and drawbacks
Table 1 | Assessment of the metabolic component of acid-base status
m compensatory, because the secondary responses The physiological approach considers the acid–base status of
Approach Variable Determination Remarks þ
lly can yield a maladaptive effect on blood pH.25,26 body fluids as being determined by net H balance (that is,
!
Physiological Plasma [HCO3 ] Measured pH and influx
PCO2 minus efflux)Interpretation complementedcomplement
and the prevailing by evaluation of plasma
of body
of an appropriate secondary response denotes the anion gap, [Na+]!([Cl!]+[Total CO2])
31,32
nce of an additional
Base excess simple
Bloodacid–base disorder.
base excess (BE) Use buffers.
CO2 equilibration The chemistry
method or calculated of acids
BE is a measure and bases
of the metabolic is blended
component with
of acid–base
tor support in critically ill patients can, of course, the empirically
from measured pH and PCO 2 derived secondary responses of the intact
status as reflected in whole blood
Interpretation complemented by evaluation of plasma !
prevent expression of the secondary changes in organism to primary changes
anion gap in PaCO2 or plasma [HCO3 ].
Standard BE (SBE)
n response to metabolic acid–base disorders.Calculated
These This approach is simple
from measured SBE is regarding
a measure of the data collection
metabolic componentandofclinical
acid-
pH, PCO2, and hemoglobin base status as reflected in the extracellular compartment.
-induced alterations are viewed as complicating application. The standard It is usuallyblood
calculated gas analyzerfrommeasures
automatically arterial bloodpH
!
respiratory acid–base disorders. The simultaneous and PCO2, from gas which plasma
results, but it can also[HCO 3 ] is
be obtained usingcalculated
the blood
acid–base nomogram with the hemoglobin! set at 5 g/dl42
of two or more simple acid–base disorders defines a (Table 1). Comparing plasma
Interpretation [HCOby
complemented 3 ]evaluation
with ofmeasured
plasma
id–base disorder. + + ++
[TCO ++ 2
] in!
venous !
blood validates this derived variable.1
anion gap
Physicochemical SIDa (apparent strong ([Na ]+[K ]+[Ca ]+[Mg ])!([Cl ]+[lactate ]) These three formulas for SIDa , as well as additional
ment of the metabolic component ion difference)is complemented Furthermore,
([Na+]+[K+])!([Cl!]+[lactate ! most acid–base
]+[other strong disorders
variants, are currently in use.are
SIDafirst recognized by
is mathematically
ating the plasma anion gap (AG), defined anions]) as clinicians through abnormalities
equivalent to the plasma in venous [TCO
buffer base 2]. and
of Singer
! 27 ([Na+]+[K+])![Cl!] Hastings64
[Cl ] þ [TCO2]), whereSID[TCO 2] indicates
e (effective strong venous
[HCO ! ! ! Although PCO2 Represents
3 ]+[Alb ]+[Pi ] where:
is universally
the sum ofconsidered
plasma [HCO! as an appro-
3 ] and non-
!
concentration (Table 1 and !
Figure 1). The[Albaverage
ion difference) ]=[Alb, g/l] #priate
[(0.123 # index of
pH)!0.631] the respiratory
bicarbonate component,
buffers plasma
(anionic equivalency [HCO
of albumin and3 ]
[Pi!]=[Pi, mmol/l] # [(0.309 # pH)!0.469]
value for plasma AG differs among
SIG (strong ion gap) health-care
SIDa – SIDe
has been viewed byphosphate) some as an unsuitable indicator of the
An estimate of the concentration of unmeasured anions
27 33,34
because of methodological variation. Normally, metabolic component. in plasma that Criticisms
resembles the include
plasma anionlackgapof inde-
Value depends ! upon the variant of SIDa used
ately 75% of the plasma AG is determined
ATot (total
pendence
byprotein,
2.43 # [total g/dl]
of plasmaPrimarily
[HCO 3 ] from
related
the respiratory compo-
to albumin concentration
27
bumin concentration. Thus, the plasma AG must nent and failure of
concentration quantitation
For clinical of buffers
purposes, approximated by the other than
concentration
of weak acids !
of total protein
ed by subtracting or adding in plasma)2.5 mEq/l from the
bicarbonate. Plasma [HCO3 ] is certainly affected by changes
All variables and electrolytes listed are expressed in mEq/l, unless otherwise indicated.
HJ Adrogué et al.: Assessing acid–base disorders Kidney International (2009) 76, 1239–1247

The physiological approach recognizes four acid–base calculated value for each 1 g/dl of plasma albumin below or
1,11–13
 METABOLISMO ACIDO-BASE

pH LEC = 7.35 - 7.45 pH LIC = 7.0 - 7.1

Hay varios mecanismos para mantener el pH en estos límites

• Tamponamiento EC • Tamponamiento IC
•  Ajuste de la PCO2 • Transporte de membrana
•  Ajuste de la excreción o de ácidos o bases.
reabsorción de ácidos o bases.
 pH

¨  pH = 6.1 + log [HCO3-]

0.03 x PCO2
[H] = 24 x PCO2/ HCO3
 Equilibrio Ac.-Base
Metabolismo Función Renal
Proteínas Equilibrio
H+ H+

pH = 7.35 – 7.45

[H+] = 40 nEq/L

[HCO3-] = 24 mEq/L

CO2 = 40 mmHg
CO2 CO2
BE = ±2
Metabolismo
(CH y L) Vent Pulmonar
AG = 12 ± 4
 Regulación homeostasis ácido-base

¨  Tamponamiento químico en LEC (HCO3)

¨  Tamponamiento químico en LIC (buffers

intracelulares: Hb, proteínas, complejos de fosfatos

orgánicos, apatita del hueso).
¨  Regulación respiratoria (PCO2)

¨  Regulación renal (conservación de HCO3 y

excreción de hidrogeniones)
Carga de ácidos

¨  Acidos volátiles
¨  Acidos fijos

¨  Acidos orgánicos
Manejo de carga ácida
 Buffers químicos

¨  Acción inmediata (segundos).

¨  HCO3 .
-

¨  Proteinas.

¨  Phosphate.
Tamponamiento intracelular
Respuesta sobrecarga ácidos
HCl
CÉLULA

H+ H+ + HCO3-

Cl-
Na + Ante una carga de ácido
• 57% intracelualr
K+ • 43% extracelular

•  La contribución relativa de cada sistema depende de la

concentración plasmática de HCO3-
•  En personas normales la contribución es muy similar, pero esto no
se aplica a otras condiciones
 Buffering intracelular

CÉLULA H+ H+

Na +
K+ H+ + HCO3-

¨  Movimiento de K+ desde la célula → ↑K+ plasmático

¤  Ácidos no orgánicos (IR, diarrea) →↑K+ 0,2-1,7 mEq/L ↓ pH
arterial 0,1
¤  Ácidos orgánicos (cetacidosis, acidosis láctica) →↑K+ 0,1-0,2
mEq/L ↓ pH arterial 0,1
Sistema Respiratorio

¨  2nd línea de defensa.

¨  Actúa en minutos, máximo en 12-24 hrs.

¨  H2CO3 producido se convierte a CO2, y es

excretado por los pulmones.
¨  La ventilación alveolar también aumenta mientras
el pH disminuye (frecuencia y profundidad).
¨  No elimina ácidos fijos.
Compensaciones

Acid Metab HCO3 PCO2 1.2mm x 1mEq HCO3

Alc Metab HCO3 PCO2 0.7mm x 1mEq HCO3

Acid Resp PCO2

Aguda HCO3 1mEq x 10mm PCO2

HCO3 3.5 “ x 10mm PCO2
Crónica

Alc Resp PCO2

Aguda HCO3 2mEq x 10mm PCO2
HCO3 4mEq x 10mm PCO2
Crónica
REGULACION A – B RENAL

¨  REABSORCION Y GENERACIÓN DE HCO3

¨  ACIDEZ TITULABLE

¨  EXCRECIÓN DE AMONIO (principal mecanismo

adaptativo renal frente a sobrecarga ácida)
 of H .
HCO3–, so the ion crosses (via Na+/HCO3– co-transporters
or HCO3–/Cl– exchangers) and then enters the blood.
Ammonium ion regulation
6. The Na+/H+ antiporter at the luminal membrane permits

Reabsorción de HCO3
transport of intracellular H+ into the tubule lumen,
enabling the process of HCO3– reabsorption to continue
(see point 1).
The buffering capacity of urinary phosphates is
exceeded in the presence of high H+ secretion. So

PERITUBULAR CAPILLARY
TUBULAR LUMEN TUBULAR PLASMA
FLUID CELL
3Na+
ATP
6 2K+
Na+ Na+ 5
Filtered 3HCO3- "Reabsorbed"
HCO3- + H+ H+ + HCO3- HCO3-
HCO3-
ATP
4 Cl-
1
H2CO3 H2CO3

2 CA
CA
H2O + CO2 H2O + CO2 CO2
3
cellular metabolism

Figure 2.1 – Cellular reabsorption of filtered HCO3–

 Acidez titulable
PERITUBULAR CAPILLARY
2 TUBULAR LUMEN
FLUID
TUBULAR
CELL
PLASMA

3Na+
ATP
1 2K+
Na+ Na+ 5
4
Filtered 3HCO3- "New"
HPO42- + H+ H+ + HCO3- HCO3-
HCO3-
ATP
Cl-
2
H2PO4- H2CO3

3 CA
CA
Excreted in urine H2O + CO2 CO2
cellular metabolism

Figure 2.2 – Cellular formation and reabsorption of “new” HCO3– coupled to H+ excretion

1. H+ leaves the tubule cell via luminal membrane Na+/H+ antiporters and H+-ATPase pumps
EXPLAINED

2. Secreted H+ that exceeds the H+ requirement for processes of HCO3– ‘reabsorption’ (see Fig. 2.1), reacts with filtered
HPO42– in the tubular fluid to form H2PO4–
M

+ –
Excreción de amonio
¨  El aumento de la excreción de NH4+ constituye la
principal adaptación ante una carga de ácido

NH3 NH3 + H+ → NH4+

¨  Tamponamiento por NH3 → ↓NH3 →↑ difusión de

NH3 hacia el lúmen
 Producción de amonio
TÚBULO PROXIMAL

NH4+
CAPILAR PERITUBULAR

LUMEN TUBULAR
Na+

Glutamina → NH4+ + glutamato → NH4+ + αketoglutarate-2

3HCO3-
2HCO3-
Na+
 Secreción de H+

CÉLULAS α INTERCALADAS
CAPILAR PERITUBULAR

TÚBULO COLECTOR

LUMEN TUBULAR
H+
H+ K+/
H+
↑
H20
↓ H+ H+
ATPa
Cl-
CO2+ OH-
sa H2PO4-
HCO3- NH4+
Respuesta a carga ácida o base
Estudio acidosis metabólica
 Stimulation of apoptosis Impaired cellular
energy production
Efectos acidosis metabólica
b a
ImpairedGeneration or
leukocyte function
exacerbation of bone disease
Decreased cardiac contractility Predisposition to
and cardiac output ventricular arrhythmias
Enhanced production Growth retardation (in children)
of
2-microglobulin Arterial vasodilation
Venoconstriction and hypotension

Chronic metabolic acidosis

Alteration in oxygen
binding to hemoglobin
Reduced albumin synthesis
Stimulation of
interleukin production
Resistance to action of
infused catecholamines
Acute metabolic acidosis Impaired glucose tolerance
Resistance to action of insulin

Increased
Changes muscle
in mental status wasting Acceleration of progression
Suppression of
of kidney disease
lymphocyte function

Stimulation of apoptosis Impaired cellular

ure 1 | Adverse effects of a | acute metabolic acidosis and b | chronic metabolic acidosis.
energy production

b
cardiovascular system most critically. Cardiac decrease
Generation or
exacerbation of bone disease in 2,3-diphosphoglycerate production occu
Acidosis metabólica

¨  HCO3
¨  pH ó [H]
¨  pCO2 (compensatoria)
¿Por qué se produce la acidosis
metabólica?

Desarrollo lento de
acidosis metabólica
Carga aguda sobrepasa
capacidad excretora
renal
¿Por qué se produce la acidosis
metabólica?
 ACIDOSIS METABOLICA

ORIENTACION DIAGNOSTICA
¨  Historia
¨  Anion Gap

¨  Gap urinario

¨  pH orina

¨  Delta Gap / Delta HCO3

¨  Kp
¨  Fe HCO3, GTTK
ANION GAP

¨  Na – ( Cl + HCO3) = 8–16 (12)

Anion Gap
 ACIDOSIS METABOLICA

ORIENTACION DIAGNOSTICA
¨  Historia
¨  Anion Gap

¨  Gap urinario

¨  pH orina

¨  Delta Gap / Delta HCO3

¨  Kp
¨  Fe HCO3, GTTK
GAP URINARIO

¨  ( Na +K ) - Cl
En acidosis metabólica con
Acidificación distal normal
GAP negativo
 ACIDOSIS METABOLICA

ORIENTACION DIAGNOSTICA
¨  Historia
¨  Anion Gap

¨  Gap urinario

¨  pH orina

¨  Delta Gap / Delta HCO3

¨  Kp
¨  Fe HCO3, GTTK
 pH orina

¨  pH mínimo en orina: 4.5

¨  Representa la eliminación de 0.5mmol de H (menos

del 1% de carga ácida diaria)

¨  Muestra no ventilada (sondeo y aspiración con

jeringa que luego debe sellarse).

[H] = 24 x pCO2/HCO3
 ACIDOSIS METABOLICA

ORIENTACION DIAGNOSTICA
¨  Historia
¨  Anion Gap

¨  Gap urinario

¨  pH orina

¨  Delta Gap / Delta HCO3

¨  Kp
¨  Fe HCO3, GTTK
 Delta

¨  En acidosis metabólica con AG aumentado:

Delta gap > Delta HCO3 (1-2:1)
¨  Cuando se suma pérdida de HCO3,

Delta gap < Delta HCO3

 Solo en Ac Metab con Anión Gap
aumentado
Delta Gap: AG calculado – AG normal
Delta HCO3: Bic normal – Bic encontrado
Delta Gap / Delta HCO3
¨  En acidosis metabólica con AG aumentado:
Delta gap > Delta HCO3 (1-2:1)

¨  Cuando se suma pérdida de HCO3,

Delta gap < Delta HCO3
Acidosis metabólica con AG elevado

¨  Historia
¨  Delta del gap – delta HCO3

¨  Lacticidemia

¨  Glicemia, cetonemia

¨  Creatininemia

¨  Tóxicos (etilenglicol, metanol etc)

¨  CPK

¨  Aminoacidemia, aminoaciduria
Manejo
¨  Tratar la causa
¨  Asegurar perfusión y oxigenación

¨  Bicarbonato de sodio en AM con pH < 7.2

considerar situación clínica, tipo de AM (AG normal o

aumentado) etc
¨  Si se requiere bolo, utilizar 0.5mEq/k y repetir c/
10-15 minutos si es necesario.
¨  Calcular déficit de HCO3 y aportar 1/3 a ½ de
acuerdo a tipo de AM y situación clínica.
Interpretación Gasometría
REGLA 1

¨  Para establecer situación ácido-base, sólo necesita

conocer:
- pH
- pCO2
- HCO3 - pH
- pCO2
- HCO3
REGLA 2

¨  Leer primero pH: ¨  pH: 7.32

determina alteración
¨  pCO2: 14
primaria (acidosis o
¨  HCO3: 7
alcalosis)
Regla 3

¨  Interpretar pCO2 y
HCO3: determinar si el ¨  pH: 7.32
trastorno es metabólico o ¨  pCO2: 14
respiratorio ¨  HCO3: 7
Regla 4

¨  Establecer si los datos de pH, pCO2 y HCO3,

son corcondantes.

[H] = 24 x PCO2/ HCO3

Regla 5

¨  Verificar si existe ¨  pH: 7.32

compensación y si ésta ¨  pCO2: 14 (20)
es la esperada. ¨  HCO3: 7
Regla 6

¨  Si la compensación no
¨  pH: 7.32
cae en el rango esperado,
¨  pCO2: 14 (20)
corresponde a un
trastorno mixto. ¨  HCO3: 7

Diag: Acidosis metabólica con Alcalosis respiratoria.

(Diagtrastorno mixto)
Regla 7

¨  Calcular siempre el anion gap

Manejo
¨  Tratar la causa
¨  Asegurar perfusión y oxigenación
¨  Bicarbonato de sodio en AM con pH < 7.2, considerar
situación clínica, tipo de AM (AG normal o aumentado) etc
¨  Si se requiere bolo, utilizar 0.5mEq/k y repetir c/10-15
minutos si es necesario.
¨  Calcular déficit de HCO3 y aportar 1/3 a ½ de acuerdo a
tipo de AM y situación clínica.
(Déficit HCO3 = % agua corporal x K x déficit HCO3)
ó aportar el total de:
Déficit de HCO3 = (12 – HCO3 actual) x agua corp. total
ects 5, 1–9 (2006).
e Care 59. Sabatini, S. & Kurtzman, N. A. Bicarbonate
therapy in severe metabolic acidosis. J. Am. Soc.
oxide Nephrol. 20, 692–695 (2009).
60. Kraut, J. A. & Kurtz, I. Use of base in the
9). treatment of acute severe organic acidosis by
of pH nephrologists and critical care physicians:
results of an online survey. Clin. Exp. Nephrol.
6, 10, 111–117 (2006).
61. Arieff, A. I., Leach, W., Park, R. & Lazarowitz, V. C.

ptors
En ac láctica, (sepsis, schock), no se ha demostrado
Systemic effects of NaHCO3 in experimental
lactic acidosis in dogs. Am. J. Physiol. 242,
n.
que el uso de HCO3 prolongue la sobrevida o
62.
F586–F591 (1982).
Halperin, F. A., Cheema-Dhadli, S., Chen, C. B. &
annel Halperin, M. I. Alkali therapy extends the period
cellularreduzca la mortalidad ni mejore la contractibilidad.
of survival during hypoxia:studies in rats. Am. J.
Physiol. 271, R381–R387 (1996).
00). 63. Stacpoole, P. W. et al. Natural history and course
nd of acquired lactic acidosis in adults. Am. J. Med.
97, 47–54 (1994).
64. Luft, D., Schmulling, R. M. & Eggstein, M. Lactic
acidosis in biguanide-treated diabetes: a review
of 330 cases. Diabetologia 14, 75–87 (1978).
65. Cooper, D. J., Hebertson, M. J., Werner, H. A. &
ates in Walley, K. R. Bicarbonate does not increase left
ac ventricular contractility during L-lactic acidemia
1993). in pigs. Am. Rev. Resp. Dis. 148, 317–322
d (1993).
13 66. Graf, H., Leach, W. & Arieff, A. I. Evidence for a
detrimental effect of bicarbonate therapy in
gers hypoxic lactic acidosis. Science 227, 754–756
. (1985).
67. Cooper, D. J., Walley, K. R., Wiggs, B. R. &
Russell, J. A. Bicarbonate does not improve
roke- hemodynamics in critically ill patients who have
nel. lactic acidosis. Ann. Intern. Med. 112, 492–498
(1990).
68. Mathieu, D., Neviere, R., Billard, V., Fleyfel, M. &
argets Wattel, F. Effects of bicarbonate therapy on
hemodynamics and tissue oxygenation in
Box 3 | Recommendations for the treatment of acute metabolic acidosis Therapies othe
■ In patients with ketoacidosis, consider administration of base if acidemia is individuals with h
severe (pH <7.1), there is evidence of cardiovascular compromise, and insulin the administration
and fluids fail to rapidly improve acidemia; aim to maintain blood pH at ~7.2 alcohol dehydroge
and monitor patient carefully acids from the me
■ In patients with lactic acidosis, consider administration of base if blood pH is or diethylene glyc
<7.1 in patients with evidence of cardiovascular compromise; aim to maintain remove the paren
blood pH at ~7.2, while carefully monitoring patient administration o
■ In patients with ketoacidosis or lactic acidosis, administer the minimum fluids and electro
quantity of base necessary to achieve the goal; estimate the quantity of base ment of ketoacido
required to raise serum HCO3– concentration to desired level using the following sis is indicated in
equation: In patients with i
Bicarbonate requirement = desired [HCO3–] – measured [HCO3–] × HCO3– space, improve tissue pe
where HCO3– space = [0.4 + (2.6/[HCO3–])] × body weight with sepsis-relat
■ If sodium bicarbonate is given, administer it slowly as an isotonic solution, with infection is crucia
the initial dose limited to ≤1–2 mEq/kg body weight As noted previo
■ Consider augmenting alveolar ventilation temporarily, particularly in individuals
dominantly hyper
with CO2 retention, while monitoring for possible barotrauma by the absence of
■ Monitor acid–base status extremely carefully, including a determination of
Therefore, the co
central or mixed venous acid–base data, particularly in patients with severe such cases depend
circulatory failure by the physician a
■ In patients with renal impairment or evidence of volume overload, consider kidney. Also, tissu
utilization of hemofiltration or dialysis onate administra
■ In patients with CO2 retention and adequate renal function, consider ischemic lactic ac
administration of THAM intact.117 Consequ
■ In patients with hyperchloremic acidosis, administer base if blood pH is <7.1; care physicians are
aim to maintain blood pH ~7.2, while carefully monitoring patient administration of
chloremic metab
Abbreviations: CO2, carbon dioxide; HCO3–, bicarbonate; THAM, tris-hydroxymethyl of organic acidos
aminomethane.
chloremic metabo
 INSULINA
GLUCOSA
INDUCIDA
HEXOCINASA GLUCOCINASA
- Km ALTA

GLUCOSA-6-P

FOSFATASAS

FRUCTOSA 6-P

FOSFOFRUCTOCINASA-1
+ AMP, +F-2,6-P, - ATP, CITRATO

FRUCTOSA 1-6-P

FOSFOENOLPIRUVATO

PIRUVATO CINASA
- FOSFORILACION DEPENDIENTE
DE AMPc
-ALANINA
+FRUCTOSA 1,6 BIFOSFATO
PIRUVATO
 Riesgos HCO3

CAMBIO BRUSCO pH

¨  Hipernatremia
¨  Hipokalemia

¨  Disminución Ca iónico

¨  Alcalosis de rebote

¨  Acidosis IC paradojal
Riesgos del uso HC03-

H+ + HCO3- ↔ H2CO3 ↔ H2O + CO2 alka

diate
cellu
HCO3- HCO3- D
pH CO2
card
pH pH
-
pH caus
HCO3 CO2 CO2 HCO3- tidal
fore,
sodiu
pH = pK1 + log [HCO3-]/[CO2] (pK1 = 6.1) bloo
FIGURE 1 by c
Fate of carbon dioxide (CO2) after administration of sodium bicarbonate. The oval indi- chem
cates the cell membrane.
clini
show
Riesgos HCO3

CAMBIO BRUSCO pH
¨  Hipernatremia

¨  Hipokalemia

¨  Disminución Ca iónico

¨  Alcalosis de rebote

¨  Acidosis IC
Acidosis paradojal

pCO2
pCO2
HCO3 HCO3
pH pH

HCO3

pCO2 pCO2
HCO3 HCO3
pH pH
Conclusiones
¨  La indicación de HCO3 en AM aguda, requiere un
diagnóstico causal y un análisis fisiopatológico de
la clínica, del A Gap y de los deltas.
¨  En acidemias orgánicas (láctica, CAD…) su

indicación es controversial salvo que el pH sea < 7

¨  En resucitación de RN y en paro CR su uso es
perjudicial.
¨  En todas las situaciones en que exista un clearence

tisular o respiratorio disminuído de CO2, su uso

acentuará la acidosis ic.