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FISIOLOGIA ACIDO BASE

QUIMICA ACIDO BASE

Ácido es un donador de protones. Puede ser


neutral, cationico o aniónico
Base es un aceptor de protones. Puede ser neutral,
cationico o aniónico.
Cuando un ácido libera un protón , se
convierte en base conjugada
Cuando una base se une a un protón, es
convertida a base conjugada.
Algunas sustancias puede ser ya sea ácidos o
bases dependiendo del medio (ejemplo:
H2PO4-)
QUIMICA ACIDO BASE

pH fue definido por Sorensen en 1909. [H+] = 10-P


= 1/10P . Donde P es potencia. La potencia de ion
hidrogeno , es llamado pH. [H+] = 10-pH, y pH = -
log10[H+]. El pH de una solución , sin embargo se
refiere a la actividad o potencia de H+.
Los ácidos y bases fuertes se disocian
completamente, tales como el HCl y NaOH.
Las bases y ácidos débiles muestran solamente una
tendencia limitada a disociarse.
HOMEOSTASIS ACIDO BASE
Fuentes generadoras de H+
• Ácidos volátiles (CO2): 15-20 mil mmol/día
• Ácidos fijos (no volátiles):
– Exógena: dieta
– Metabolismo endógeno
Ü Acidos inorgánicos
Sulfatos, fosfatos
Ü Acidos orgánicos:
Acido láctico
Cetoácidos
Equilibrio ácido-básico

60 mEq/día

Ingreso H+ Egreso

40 nEq/l 60 mEq/día

0.000000040 Eq/l
Escala de pH (Sorensen)

- log [H+] = pH

- log [10-1 Eq/l] = pH 1


- log [0.1 Eq/l] = pH 1
Escala de pH
• pH • [H+] en Eq/l
1.0 0.1
2.0 0.01
3.0 0.001
4.0 0.0001
5.0 0.00001
6.0 0.000001
7.0 0.0000001
7.4 0.000000040
8.0 0.000000010
9.0 0.000000001
Manejo de la carga ácida diaria
• Tamponamiento extracelular

• Tamponamiento intracelular

• Compensación respiratoria

• Excreción renal de la carga neta de ácido


QUIMICA ACIDO BASE

Acetic acid (weak) dissociates as follows: CH3COOH <=> H+ + CH3COO-. The


equilibrium constant is:
[H  ][CH 3COO  ]
Keq   1.8x105 at 25o C
[CH 3COOH]
This
What is called
is the pH ofthe ionization
a solution constant 1ormol/L
containing Ka. Therefore, pKa =
of acetic acid? -log10
First, Ka = 4.74.
assume that
both ions exist in equal amounts, and second, that CH3COOH is practically 1
mol/L. Therefore,

[H  ]2
 1.8x105 mol / L and [H + ] = 0.0042 mol / L, pH = 2.38
1 mol / L

In the case where [CH3COO-] = [CH3COOH] = 0.1 mol/L, which can be


accomplished by adding Na+CH3COO- in an equal amount, then

[H + ] x 0.1 mol / L
 1.8 x 10-5 mol / L
0.1 mol / L

[H+] = 1.8 x 10-5 mol/L, and pH = 4.74. In this special case, pH = pKa.
BUFFER SYSTEMS 1

Buffer solutions have the property of showing only small changes of pH


when an acid or base is added, within limits. A buffer solution is
prepared by mixing a weak acid with its conjugate base, i.e. the salt of
the acid (e.g. CH3COOH and Na+CH3COO-). A buffer solution can also
be prepared by mixing a weak base with its conjugate acid.
If we add NaOH to an acetic acid/sodium acetate buffer solution the
following reactions occur:
NaOH => Na+ + OH- completely, then CH3COOH releases a proton
(CH3COOH <=>H+ + CH3COO-) to neutralize the OH- ions, producing
the reaction OH- + H+ <=>H2O, and the change in pH will be minimal.
Continuing to add NaOH will produce further dissociation of acetic acid
until the concentration of acetic acid is significantly reduced. Then
addition of more NaOH will have a greater impact on pH. Adding HCl
will have the opposite effect. H+ ions will bind to CH3COO-, producing
the weak acid CH3COOH, minimizing the change in pH.
BUFFER SYSTEMS 2

The buffering capacity of a solution depends on the concentration of the


two components, and the ratio of the [conjugate base] to the [weak
acid]. The maximum buffer capacity of a solution occurs when
[conjugate base] = [weak acid], which is the same as saying that pH =
pKa. Remember, the same conditions apply if we are using a weak
base and its conjugate acid in the buffer solution.
In general, HA <=> H+ + A-, and BA <=> B+ + A-.

[H  ][A  ] [A  ]
Ka  and pH  pKa  log10
[HA] [HA]

This is the Henderson-Hasselbalch equation.


THE BICARBONATE/CARBONIC ACID SYSTEM 1

CO2 + H2O <=>H2CO3 <=>H+ + HCO3-


[H 2 CO3 ] [H  ][HCO3 ]
K1  and K2 
[H 2 O][CO2 ] [H 2 CO3 ]
Rearrange the first equation to solve for H2CO3 and substitute this value in the
 
second equation giving: K 
[H ][HCO 3 ]
2
K1[H 2 O][CO2 ]
and since the value for H2O is constant, we can multiply both sides of the
equation by K1H2O and incorporate it into the equilibrium constant to produce
[H  ][HCO3 ] [HCO3 ]
K 
'
1 ; therefore, pH = pK1  log10
'
[CO2 ] [CO2 ]
We do not measure [CO2], instead, we measure PCO2. Because we know that the
amount of CO2 dissolved in plasma is proportional to plasma PCO2, then [CO2] =
a*PCO2. The pK for this equation (bicarbonate/carbonic acid) is 6.1 and the
constant of proportionality between [CO2] and PCO2 (a) is 0.03. Therefore,
[HCO3  ]
pH  6.1  log10
0.03* PCO2
THE BICARBONATE/CARBONIC ACID SYSTEM 2

Now let’s explore the relationship between [bicarbonate] and [CO2].


[HCO3  ]
pH  6.1  log10
If we substitute the normal values for bicarbonate (24
0.03xPCO 2 mmol/L) and PCO2
(40 torr), then pH = 7.4. To determine the conditions
(bicarbonate/CO2 ratio) needed to maintain pH at 7.4, subtract pK from
both sides of the equation, then

[HCO3 ]
1.3  log10
[CO2 ]
The ratio of [bicarbonate] to [carbon dioxide] must be 20:1 for the
equation to be true; therefore, if the bicarbonate concentration falls to
12 mmol/L, and the concentration of CO2 is reduced by half, pH will be
7.4. This compensation works because the ratio is once again restored.
If the ratio exceeds 20:1, either the [bicarbonate] is high or the [CO2]
is low. In other words, alkalosis. Acidosis occurs when the ratio is less
than 20:1.
NOTES

In a closed in vitro system, the bicarbonate/carbonic acid system is not an


effective buffer. In vivo, however, the lungs and kidneys can influence the
acid-base balance of plasma efficiently because one system can
compensate for a failure of the other.
There are many other buffer systems, both intra- and extra-cellular. The more
important being hemoglobin, plasma proteins, erythrocytic 2,3-DPG, and
organic and inorganic phosphate.
Hemoglobin is an important buffer because it occurs in high concentration, and
has a pK of about 6.8. Hydrogen ion affinity varies with oxygen saturation.
In the systemic capillaries and venous blood where O2 saturation is low, the
H+ affinity is high. The importance of this should not escape anyone
because these are the regions of low pH.
CO2 + H2O <=>H2CO3 <=>H+ + HCO3-
+
Hb- <=>HbH
Therefore, as H+ are removed by hemoglobin, the reaction, beginning with
CO2, is driven to the right, producing more HCO3-
SISTEMA ÁCIDO - BASE

CO2 H+

HCO3-

CO2 + H2O H2CO3 H+ + HCO3-


ALCALOSIS METABOLICA

CO2 H+

HCO3-

CO2 + H2O H2CO3 H+ + HCO3-


Respuesta: Problema:
Hipoventilacion Perdida de iones H+ .
Incremento [CO2]
Incremento [HCO3-] alto.
[H+]
Acidosis metabólica

CO2 H+

HCO3-

CO2 + H2O H2CO3 H+ + HCO3-


Respuesta: Problema:
Hiperventilación Exceso de iones H+
[CO2] Disminuye Disminución [HCO3-] bajo.
[H+]
ALCALOSIS RESPIRATORIA

CO2 H+

HCO3-

CO2 + H2O H2CO3 H+ + HCO3-


Problema: Respuesta:
Hiperventilación Disminuye
Baja PCO2 excreción H+ .
Aumento Disminuye
+
[H ] Bajo [H+] producción HCO3-
.
Acidosis respiratoria

CO2 H+

HCO3-

CO2 + H2O H2CO3 H+ + HCO3-


Problema: Respuesta:
Hipoventilacion Incrementa
PCO2 Alto excreción H+.
+
Disminuye Incrementa
[H ] Alto [H+] producción HCO3-
.
THE ROLE OF LUNGS AND KIDNEYS IN ACID-BASE BALANCE 1

From the previous section, we saw that the ratio of HCO3- to CO2 was the important
determinant of pH. CO2 being controlled by the lungs are called the
“respiratory” component in acid-base physiology. Bicarbonate being controlled
by the kidneys is called the “metabolic” or “renal” component. In a normal
person both the lung and kidney work to maintain the 20:1 ratio
When the kidney fails to excrete enough hydrogen ions, and fails to recover a
sufficient amount of bicarbonate, the condition is called metabolic acidosis. In
other words, the HCO3- to CO2 ratio is less than 20 to 1, and pH will be low.
Some causes are diabetic ketosis, acid toxication (acetylsalicylic acid), and lactic
acidosis (heavy exercise). Because CO2 is now high, the lungs will eliminate
larger amounts of CO2 by hyperventilation, restoring the ratio to __:__. (fill in
the blanks.)
When bicarbonate is in excess, the condition is called metabolic alkalosis (ratio >
20:1). This can be caused by acid depletion such as after severe vomiting, or
by ingestion of large amounts of sodium bicarbonate. In a normal person, this
alkalosis will cause the individual to hypoventilate and retain CO2, restoring the
_____.
THE ROLE OF LUNGS AND KIDNEYS IN ACID-BASE BALANCE 2

Respiratory compensation does not completely restore the 20:1 ratio. Imagine that
a person has a metabolic alkalosis; therefore, the person hypoventilates to
increase [CO2]. This new higher [CO2] stimulates ventilation. That is, the
attempt to correct inhibits the correction. Full compensation for metabolic
acidosis will likewise fail for the same reason.
Respiratory acidosis occurs when the lungs are incapable of eliminating a sufficient
amount of CO2 to maintain pH at 7.4 (ratio < 20:1). This CO2 retention may be
caused by a bronchopulmonary disease or by a reduction in chemosensitivity to
CO2 (barbiturate toxication). It is the responsibility of the kidney to excrete H+
and bring about an increase in bicarbonate concentration.
Respiratory alkalosis is brought about by excessive elimination of CO2 from the
lungs. pH will rise because the ratio is greater than 20:1. Hyperventilation may
be caused by anxiety, fever, anemia, and by some drugs. It is the role of the
kidneys to reduce the excretion of H+, thereby reducing the production of HCO3-
.
Normally functioning kidneys can completely restore pH. In fact, the kidney may
respond by overcompensating, producing a secondary metabolic disturbance.
In general, if the primary disturbance is metabolic, respiratory compensation occurs
immediately, but not fully. In contrast, when the primary disturbance is
respiratory, metabolic (renal) compensation takes several days to complete.
ANION GAP 1

Because of the law of electroneutrality, positive and negative


charges must be balanced (i.e., the sum of all cations must
equal the sum of all anions). However, we do not usually
measure all ionic components of blood. Laboratory results will
report sodium, potassium, chloride, and bicarbonate
concentrations. If these are the only ions reported, there will
be a difference in the sum of the cations and the sum of the
anions with the cations being greater. This difference is called
the anion gap. Anion Gap (AG) = (Na+ + K+) - (Cl- + HCO3-).
Many books ignore potassium because it is in low concentration
in plasma. When evaluating anion gap, be sure to determine
whether the published values include potassium, most do not.
ANION GAP 2

Anion Gap is most useful in classifying metabolic acidosis into two


types:
Acidosis with high anion gap. This is the condition seen in renal
failure, ketoacidosis, lactic acidosis, and toxication with
paraldehyde, methanol, ethylene glycol, or salicylate. High
anion gap occurs when the conjugate base of the acid added is
not Cl- or HCO3-. Furthermore, the added H+ ions will combine
with HCO3-, increasing the anion gap.
Acidosis with normal anion gap. This is seen in patients with
renal tubular acidosis, diarrhea, or after treatment with carbonic
anhydrase inhibitors, HCl, NH4Cl, or arginine-HCl. If the acid
added binds HCO3-, but the anion released is Cl-, the sum of the
anions will not change, and the anion gap will be normal.

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