Acid base balance

(H homeostasis)
+

Dr. Rochana Perera

Importance of H

Is the H+ nucleus ( proton ) without the orbital

electron.
Is the smallest atom ( nucleus ).
Very active. Binds with any negative ion, such
as proteins.
Changes the properties of proteins (enzymes)
or destroy it (denature).
Influences ionic dissociation & movements
Affects chemical & drug reactions.

Importance of p H

Expression of H concentration
+

Daily acid load is about 15000 20000 mmol H +

from CO2 and 40 - 80 mmol from metabolism.

Expressed in either arithmetic ( nmol/l ) or

logarithmic ( p H = - log H+) scale.

In chemistry, p H 7 ( water )is considered as

neutral. In physiology, p H of 7.4 (art.blood) is

considered as neutral.

As logarithmic scale ( p H ) is non-linear, arithmetic

scale is becoming popular.

p H vs. H+ concentration
pH
7.8

7.7

7.6

7.5

7.4

7.3

7.2

7.1

7.0

H+

6.9

6.8

20 25 32changes
40 50
63 80 100 125 160
H+16concentration
non-linearly.
To change from 7 to 7.4 requires 60 nmol, whereas

Conc.

from 7.4 to 7.8 needs only 24 nmol change.

 Distilled water is relatively

acidic compared to blood.

Infusion of common

intravenous fluids ( saline,

dextrose, Hartman's etc)
cause acidosis ( dilutional
acidaemia ) whereas
dehydration causes alkalosis
(contractual alkalaemia).

Definitions
Acidosis

A process that causes acids to accumulate.

Acidaemia
p H below 7.36
Alkalosis
accumulation of base
Alkalaemia
p H above 7.44

Definitions - contd
Acid

A substance capable of donating a proton(H+).

Strong acid

an acid which dissociates almost completely (eg;

HCl)
Weak acid

An acid which dissociates partially

(eg;H2CO3)
Strong ion

a substance which is totally or nearly totally ionized.

ionized

Definitions - contd
Base

A substance capable of accepting a proton ( OH- ).

Alkali

A salt containing base.

Eg; NaOH, Ca(OH)2
Buffer

A combination of a weak acid and its

conjugate base ( H2CO3 / NaHCO3 )

Buffer solutions
A buffer is a solution containing two or more

compounds that prevents changes in H+

concentration.
Usually contains a weak acid & its salt
( NaHCO3 / H2CO3 ).
H+ combine with the HCO32- to form H2CO3

which is weakly ionized. Any addition of HCO3

would combine with the H+ resulting the same.

Henderson Hasselbalch equation

Traditional way of teaching acid base balance.
p H = p KA + log (base / acid ) = p KA + log ( HCO3 /

CO2 )

p KA is the p H when equal amounts of acidic and basic

compounds are present (dissociation constant).

For the normal cellular function, the arterial p H needs to

be maintained within 7.36 to 7.44. Values above 8.0 or

below 6.8 are not compatible with life.

According to this theory

Increased CO2 would reduce the p H,

whereas high bicarbonate would increase it.

Hydroxyl ion concentration is not an important
determinant of p H.
No differentiation between respiratory &
metabolic HCO3.
Hence the need for standard HCO3 and base

excess.

Standard bicarbonate
The concentration of HCO3 when respiratory

contribution is eliminated.
Is the amount of HCO3 present in a liter of
blood having a Pco2 of 40 mmHg.
Normal value is 24 27 mmol / l.
Is reduced in metabolic acidosis and

increased in metabolic alkalosis.

Base excess / deficit

The amount of base, in mmol, required to be

added or removed to/from a liter of blood to

titrate it back to a p H of 7.4 when the p CO 2
is 40 mmHg.
Up to 5 mmol / l (+ or -) is considered normal.
Anything above that is metabolic alkalosis.
Metabolic acidosis is when the BE is less
than -5 mmol / l ( base deficit ).

Stewarts physico chemical

theory
An alternative theory to H H equation.
H+ derives from water dissociation.
This dissociation depends on only 3

independent variables.

strong ion difference (SID)

p CO2
total weak acid concentration (ATOT)

HCO3 merely reflects acid base state, but

as a dependent variable, can not affect the

p H on its own.

Strong ion difference (SID)

Net charge balance of all the strong ions present.
(Na + K + Ca + Mg) (Cl + lactate) is called the

apparent SID (SIDa). It is normally + 40 42 meq /

l.
Effective SID (SIDe) is the difference between the
(Na+K+Ca+Mg) (Cl + lactate +HCO3 + A- )
As the SID becomes more positive, H+

concentration decreases to maintain the

electrical neutrality.

Total weak acid concentration (ATOT)

Conjugates of the weak acids ( mainly albumin &

phosphates ) concentration.
Both the dissociated & the conjugated
components are taken in to calculation.
Therefore it is independent of the % of dissociation
and factors affecting dissociation such as p K.

Strong ion gap (SIG)

SID must be equal to the total of HCO3, P04 and

albumin concentrations.
If not, an unmeasured anions must be present .
This gap is called the SIG.
Should be equal to the OH- concentration in a
healthy person.
SIG is not affected by the p H or the albumin.
SIDa = SIDe +SIG.

Electrical neutrality cant be corrected by the

creation or destruction of a strong ion, but by
changes in water dissociation to produce or
consume H+.

Explanation of dilutional acidaemia

Traditional theory

Water dilutes HCO32- ions in the blood, so p H

increases.

HOWEVER

Shouldnt that dilute the H+ by the same %

and maintain the ratio ?

Explanation Stuarts theory

A liter of plasma contains about

150 mmol of strong cations (Na &

K ) and about 110 mmol of strong
anions (Cl & lactate). SIG 40.
Addition of a liter of water would
dilute it to 75 mmol of cations and
55 mmol of anions with a SIG of
20.
Reduced SIG makes the solution
acidic by increasing the water
dissociation.

Vomiting causes alkalosis- explanation

Loss of H+ as HCl increases the base / acid

ratio.
In Stuarts theory
Loss of Cl- loss widens the SIG. As a result,
water dissociation is reduced.
This condition is corrected by giving NaCl
infusions, which corrects the Cl- concentration.

Defense mechanisms against p H

changes

BUFFER SYSTEMS (chemical buffering)

RESPIRATORY (physiological buffering)
RENAL

Buffer mechanisms
The first line of defense. Acts within a fraction

of a second.
Efficiency (buffering power) depends on 2
major factors.
Concentrations of the both components.
p K of the buffer system.

As a result, the human body can tolerate

acidaemic changes better than alkalaemia.

Titration curve of a buffer

Bicarbonate buffer system

Found in the blood & ecf.
The p K of the system is 6.1.
The concentrations of CO2 and HCO3 are relatively small, but

could be regulated by the lungs and kidneys respectively (open

system).
HCl + NaHCO3
H2CO3 + NaCl
NaOH + H2CO3
NaHCO3 + H2O

Both the NaHCO3 & the H2CO3 are weakly ionized, so the effect on

p H is minimal.

Phosphate buffer system

HCl + Na2HPO4 NaH2PO4 + NaCl
NaCl + NaH2PO4

Na2HPO4 + H2O

Found in the renal tubules and bone matrix.

The p K is 6.8.
Its concentration in ECF is less than 10 % of

the bicarbonate system.

Phosphate & H+ concentration in ICF is many
times higher, so the buffering capacity is
increased in ICF.

PO4 buffer in renal tubules

3-

Protein buffer system

The most plentiful buffer.
Is found in ICF as well as in ECF (albumin)
As HCO32- & CO2 diffuse through the cell

membrane, icf proteins help to buffer ecf p H.

But it takes several hours.
About 75% of chemical buffering is due to
proteins.
p K of some amino acids is about 7.4.

Haemoglobin
Reduced Hb is a potent ecf buffer as both H + and CO2

could bind with it.

2 mechanisms for CO2

CO2 directly bound to Hb to form carbaminoHb.

Dissolves within the RBC.
Cl shift for HCO 2- .
3

For H+
Directly binds to reduced Hb to form HHb.
P Ka ?
More effective in tissues and in venous blood ( reduced).

Isohydric principle
Buffer systems buffer each other by

shifting H+ from one to another.

As a result, when H+ concentration changes,
balance of all the buffer systems change at
the same time.
The % involvement of the each system is
decided by the relative buffering capacity of
the individual buffer (depending on p K and
the concentration).

Respiratory regulation
A physiological buffer.
Increased CO2 decreases the p H and vice

versa.( Henderson-Hasselbalch equation )

Comes into effect within 10 -12 min.
Normally CO2 concentration in ecf is 1.2
mmol/l.( p CO2 = 40 mmHg )
Increased p CO2 stimulates respiratory center

to wash out CO2.

CO2 wash out curve

The p H changes

exponentially.
MV x 2 = p H 7.63
MV / 4 = p H 6.95
MV could be reduced
to near zero or
increased upto 15
times.

Efficiency of resp. control

It never brings the p H back to 7.4 as the

stimulus decreases gradually.

Only 50 75% efficiency ( brings the p H
from 7.0 to 7.2 - 7.3 )
Buffering power is about twice the power of
all the chemical buffers combined together.

Renal control
Can take many hours to few days to produce

full effect.
Can bring back the p H to 7.4 exactly, but
never overcorrects.
Therefore it is the most powerful of all the
regulatory systems.

H+ secretion
H+ are secreted into

the tubule.
Na+- H+ counter
transport at PTC.
Primary active
transport in DCT
(5%).
Normal rate of
secretion is about
3.5 mmol/l.

blood

Buffering of urinary H

Tubules can not tolerate a p H below 4.5

(0.025 mmol / l).

Daily elimination is 40 mmol /l
As H+ secretion stops at p H below 4.5,
buffering urinary H+ is very important. .
Phosphate & ammonia are the 2 main
buffers.
Uric acid / urate & citric acid / citrate are also
found in urine.

NH3 / NH buffer
+
4

NH3 is produced in the renal tubules from

glutamine (60%) by the enzyme glutaminase.

Glutaminase production is induced in chronic
acidosis.
NH3 + H+
NH4+
NH3 diffuses out along the concentration
gradient. When it combines with a H+ ,tubular
NH3 drops allowing more molecules to diffuse
out.
NH3 production is therefore regulated by the
H+ .

NH4 Buffer
+

HCO3 reabsorption
2-

Is filtered at a rate of

3.46 mmol/l.
Reabsorption occurs
in DCT.
It first combines with
a H+,then dissociates
into CO2 & H2O.
Within the cell, CO2
forms a HCO3 which
diffuses out.

Renal correction of acidosis

In acidosis CO2 / HCO3 ratio is high.

Rate of H+ secretion exceeds HCO3 filtration.
As a HCO3 is needed to reabsorb a H+,excess H+ are

lost in urine.

Renal correction of alkalosis

Less H+ are secreted than the HCO3 filtered.
Less HCO3 is reabsorbed; rest lost in urine.
To maintain the electrical neutrality Cl-

concentration increases.

Respiratory acidosis
Caused by the accumulation of CO2.
Is another name for hypercarbia.
Caused by decreased minute ventilation such

as in central depression, neurological

disorders, air way obstruction etc.
In an ABG report, p H is low and pco2 is high.
Compensatory resp. acidosis in met.

alkalosis.

Respiratory alkalosis
Due to CO2 wash out ( hyperventilation ).
Occurs in hysteria, IPPV, asthma &

pneumonia ( type 1 respiratory failure )

ABG shows a high p H and a low pCO2.
Compensatory resp. alkalosis in met.

acidosis.

Mx of resp. disturbances
Respiratory acidosis

A p H up to 7.2 may be managed without IPPV.

IPPV for severe acidosis.
NaHCO3 is contraindicated in resp. acidosis.
Respiratory alkalosis
Reduce MV in IPPV
Treat the cause
Symptomatic treatment
Anticonvulsants
Ca gluconate

Metabolic alkalosis
Accumulation of HCO3.
Chloride responsive(urinary Cl- below 20mmol / l).

Acid loss
Vomiting ( upper GI )
NG suction
Gastro-colic fistula
Chloride depletion
Diarrhoea
Diuretics (except carbonic anhydrase inhibitors)
Excessive alkali intake
NaHCO administration
3
Antacid abuse

Metabolic alkalosis contd.

Chloride resistant (urine Cl- over 20 mmol/l)

Hyperaldosteronism
Cushings syndrome
Severe hypokalaemia
carbenoxalone

Met.alkalosis- Mx
Cl- sensitive

Normal saline
H2 antagonists ( in NG loss )

KCl to correct K+
Cl- resistant
Correct the cause
acetazolamide

Metabolic acidosis
Anion gap

is the difference between Na+

(140) + K+(4) and Cl- (105) and
HCO3(22).

Normal anion gap is about 12 -

17mmol/l.
In hypoalbuminaemia and

hypophosphataemia. (critically ill)

AG = (0.2 x albumin g / l) + (1.5 x

phosphate mmol / l)

Metabolic acidosis
Low HCO3 and p H
High anion gap

Acid overproduction

Exogeneous acid

Diabetic ketoacidosis
Lactic acidosis type A ( hypoxia, shock )
Lactic acidosis type B (biguanides)
Salicylates
Methanol

Reduced excretion

Renal failure

Normal anion gap

Bicarbonate loss

Extrarenal
Diarrhoea
Billiary / pancreatic fistula
Ileostomy
Uretero-sigmoidostomy
Renal
Renal tubular acidosis
Acetazolamide
Addition of acid ( with Cl- )
HCl, NH4Cl, arginine / lycine hydrochloride

Mx metabolic acidosis
Normal anion gap

Treated with NaHCO3.

Dose = BW ( kg ) x base deficit x 0.3

According to Stuarts theory

If the BE is to be reduced from 15 to 5, SID must

be increased by 10 mol / l. NaHCO3 acts by
increasing the Na concentration, thereby
reducing the SID.

High anion gap

Correct the cause

Interpretation of ABG results

Primary
disorder

PH

Std.HCO3

PaCO2

compensatio
n

Metabolic
acidosis

low

low

normal

High MV
( low CO2)

Metabolic
alkalosis

high

high

normal

Low MV
( high CO2)

Resp.
acidosis

low

normal

High

HCO3
retention

Resp.
alkalosis

high

normal

low

HCO3
excretion

Interpretation of ABG
P H 7.31
P CO2 48 mmHg
P O2 121 mmHg
BE 1.6 mmol/l
Std.HCO3 25 mmol/l

PH 7.34
Pco2 48
pO2 121
BE 5.2
Std HCO3 31.4

Interpretation
P H 7.2
P CO2 34

PH 6.8
P CO2 61

PO2 87
BE 6.8

P O2 96
BE 16

Std HCO3 18

Std HCO3 9

Merry Christmas
&
Happy new year