Chapter VII.
Acid –Base Disturbance
Section 1. Acid-Base Balance
Section 2. Simple types of acid-base
disturbance
Section 3. Mixed Acid-base Disturbance
1
Section 1. Acid-Base Balance
(1) Sources of acid and base
(2) Regulation of acid-base balance
(3) Laboratory parameters of acid-base
balance
2
Homeostasis is very important for
life. Acid-base balance is one of the major
requirements ( volume, osmolarity of the
body fluid, etc.).

The basic meaning of acid-base
balance is the stable [H+] in the body fluid.

3
(1) Sources of acid and base
The main origin of acid and base is
the intracellular metabolism (catabolism of
protein, carbohydrate and fat).
4


Two kinds of acids are formed from
metabolism: 1) volatile acid,
2) nonvolatile acid.

The volatile acid is the acid, which
can be eliminated from lung (respiration).

The nonvolatile acid has to be
eliminated from kidneys within urine.
5
1) Volatile acid

The CO2 is the end-product of oxidative
metabolism of protein, carbohydrate and fat. The
daily production of H+ (H2CO3) is 13~15(20) Mol.

H2CO3 can be dissociated to form hydration
(H2O) and CO2.



CA
(carbonic anhydrase)
H2CO3 ←--→H2O+ CO2
The CO2 can be eliminated from pulmonary
expiration, so H2CO3 is volatile acid.
6
2) unvolatile acid (fixed acid)

Uric acid, phosphoric acid (H3PO4) and sulfuric
acid (H2SO4) are the products in the metabolic
process of proteins and nuclear acids.

Lactic
acid
and
ketonic
bodies(βhydroxybutyric acid β-羟丁酸and acetoacetic acid 乙
酰乙酸) can be formed from the metabolic process
of carbohydrate and fat as intermediate products,
when the oxygen supply is not sufficiency.

([H+]=70~100 mmol/ per day)
7
3) Base
The production of acid (H2CO3, organic
acids) is much more than the production of
base (deamination of AA―>NH3) from the
metabolism in normal diet.
The vegetables, and fruits also
contains some base (such as citrate (柠檬酸
盐) oxalateis(草酸盐) the H+ acceptor ).
Citrate + H+ = citric acid
8
(2) Regulation of acid-base balance




1)
2)
3)
4)
Chemical buffers
Respiratory regulation
Renal regulation
Cellular regulation
9
1) Chemical buffers
Buffer pair (buffer system) consists of a weak acid and
its’ salt, such as

NaHCO3 Na2HPO4 Hb- PrHbO-2
----------- ------------ ----- ----- ---------H2CO3
NaH2PO4 HHb HPr
HHbO2
H2SO4 (sulfuric acid) + NaHCO3 = Na2SO4 + H2CO3

A strong acid (H2SO4, HCl) become a weak acid after
combining to NaHCO3 -. A strong base becomes a weak base after
combining to H2CO3.

Minimal changes of [H+ ].

Immediately available (first defense line)
10
buffer system
the % account
----------------------------------------------------------------------------------HCO-3/H2CO3
53%
Hb-/HHb
HbO-2/HHbO2
35%
Pr-/HPr
7%
Phosphate
5%
-------------------------------------------------------NaHCO3 can be effectively eliminated by
kidneys and (H2CO3 ←→H2O + CO2) CO2 can be
effectively eliminated by the lung.
HCO-3/H2CO3 is the most important buffer pair.
11
2) Respiratory regulation
Increased PaCO2 (>60mmHg, 8kPa)
decreases pH of ESF, which can stimulate
the respiratory center via central
chemoreceptors and increase the depth of
respiration (hyperventilation, tidal volume
increased).
12
High PaCO2
Low pH of
ESF
via
central
chemoreceptors
stimulate the respiratory center
increase the depth of respiration
more carbon dioxide can be
eliminated from lung
normal
PaCO2
normal pH
13
Increased PaCO2 (>60mmHg, 8kPa) and
decreased pH can both stimulate the
respiratory center via peripheral
chemoreceptors and increase the depth of
respiration (hyperventilation, tidal volume increased).
More CO2 can be eliminated from lung, so
that the [H2CO3] in blood will fall to normal
range, the pH will increase to normal by regulate
the ratio of [HCO3-] and [H2CO3] .
14
Higher pH and low PaCO2 will inhibit
the respiratory center, the depth of
respiration will decrease (hypoventilation),
the CO2 will increase in the blood, then
[H2CO3] in blood will increase to normal and
pH will decrease.

15
Characteristic of respiratory compensation
(a) Timeliness.
The respiratory response begins within
several minutes.
The respiratory response often takes 30
minutes for the respiratory compensation.
12~24 hours to get maximal compensation.
16

(b) The degree of ventilatory response
([H2CO3],PaCO2) is proportional to the degree
of metabolic acidosis or alkalosis ([HCO3¯ ]).
The degree of compensation
(decrease of [H2CO3]) may be
predicted by the decreased level of
[HCO3¯ ]. Some equations have been
developed for the prediction.
There is s maximum of limitation of compensation
Significance.
17
(c) Normal PaCO2 = 40 mmHg
40―>60mmHg: stimulates respiratory
center.
80 mmHg―>:
inhabits respiratory
center.
(CO2 narcosis, CO2麻醉)
18
3) Renal regulation
Renal compensation begins from several
hours after the addition of acid load, and it may
take 3~5 days to reach the maximum of this
compensatory capacity.
Kidneys play a major role in the regulation of
pH in the body.
The renal regulation consists of two
processes.
19
(a) Excretion of acids
a)Secretion of H+, NH4+
b)Excrete all the nonvolatile acid (70~100
mmol/ per day) produced from catabolism of
food.
(b) Reabsorb properly the bicarbonate filtered
from glomerulus.
When the pH is decreased, more
bicarbonate needs to be reabsorbed.

If the pH is increased, more bicarbonate
will be eliminated.

20
Mechanisms of H+excretion and HCO3–
reabsorption:
① in proximal tubule:
Via Na+ - H+ antiportor (NHE反向转运体)
Via actively secretion of H+
Via secretion of NH3/NH4+
② in distal tubule+collecting duct
H+ -ATPase
H+ -K+ATPase
Cl- -HCO3- exchanger
21
① in proximal tubule:
(a)Na+-H+反向转运体antiportor NHE
细胞内CA碳酸酐酶催化H2O+CO2形成H2CO3, 再解离为H+ 和HCO3管腔膜有Na+ -K+ ATP酶保持低[Na+]i(浓度差),促经NHE,细胞内H+进小管液,
小管液Na+进肾小管细胞, 再结合HCO3 -,经基侧膜Na+ -HCO3 -载体同向重吸收,
结果: 小管上皮细胞向管腔液分泌1mol H+,同时血浆增1mol HCO3-
肾小管细胞内CO2来自于肾小管
腔.管腔内CO2来自于上游HCO3 实为血液中HCO3-,滤过后重吸收.
由NHE排出的H+,和HCO3 -形成
H2CO3,再形成CO2,也被重吸收入肾小
管上皮细胞.
最终只有H2O排出.
22
① in proximal tubule:
(b) Actively secretion
of H+

通过管腔膜H+ATP酶主动耗能将H+
分泌至肾小管腔内.

尿液酸化.

23
① in proximal tubule:
(c)Via secretion of NH3/NH4+
谷氨酰胺在谷氨酰
胺酶(GT)作用下,形成谷
氨酸, 再形成NH3和α-酮
戊二酸， 后者再形成
HCO3-。
NH3+H+形成NH4+ ，
由Na+-H+反向转运体
（NHE）进入小管液。
HCO3-经基侧膜Na+ HCO3-载体同向重吸收。
24
非离子扩散形式泌NH3 ：
肾小管中的NH4+在
髓袢升支粗段再分解为
H+和NH3， H+通过NHE
（Na+-H+反向交换体）
泌出，而NH3弥散到集
合管，与集合管上皮泵
出的H+形成NH4+排出。
使尿液进一步酸化.
NH4+是水溶性.
25
② in distal tubule+collecting duct
α闰细胞（泌氢细胞）非
Na+依赖性向管腔泌H+
在管腔膜通过：
(a) H+-ATP酶向管腔泌H+;
(b) H+-K+ ATP酶泌H+换K+
使尿液酸化（H2PO4-和NH4+增
多）
在基侧膜经交换Cl-,回吸
收HCO3-进血。
β闰细胞通过基侧膜H+ATP酶向血液排H+ ；通过管腔
膜向管腔排HCO3-与Cl-交换，
使尿液碱化。
26
Phosphate
There are two kinds of
phosphate in urine:
(1) dibasic form
(Na2HPO4 ) and
(2) monobasic form
(NaH2PO4 ).
Na2HPO4 + H+ ←→ NaH2PO4 + Na+
27
Most of the
phosphate in the
glomerular filtrate is
dibasic form (Na2HPO4 )
with buffering function.

There is more
NaH2PO4 in the final urine
as the result of combining
H+.

When the final
urine pH is 4.8, 99% of
phosphate is NaH2PO4 at
the same time the more
NaHCO3 is reabsorpted.

28
4) Cellular regulation

(a) H+-K+ exchange

(b) Cl¯ - HCO3¯ exchange

(c) Utilizing of bone salt

(d) Synthesis of urea from NH3
29
(a) H+-K+ exchange
When [H+] in ECF
(serum) is increased, the
H+ will move into the
cells, as a exchange for
electrical neutrality, K+
will shift from ICF to the
ECF. So the pH of ECF
(serum) will increase to
normal, but
hyperkalemia may occur.
30
(b) Cl ¯ - HCO3¯ exchange

When CO2 in ECF(serum) is increased, CO2 will
move into the cells, CO2 combines H2O to form
carbonic acid, then H2 CO3 dissociates to form H+
and HCO3¯ , the HCO3¯ moves out of the RBC,for
neutrality, Cl ¯ moves into the cells.
31
© Utilizing of bone salt
In chronic metabolic acidosis, bone
salt, Ca3(PO4), is also utilized as a buffer
base, but the expense is decalcification of
bone and osteoporosis (loose and soft bone).
Ca3(PO4)2 + 4H+ ←→ 3 Ca2+ + 2 H2PO4 ¯
Is it a good way of regulating acid-base
balance ?
(d) Synthesis of urea from NH3 in liver cells.
32
(4) Laboratory parameters of acid-base
balance
1) pH
 2) PaCO2 (partial pressure of carbon dioxide in

arterial blood)
 3) Standard bicarbonate (SB)

Actual bicarbonate (AB)
 4) Buffer base (BB)
 5) Base excess (BE)
 6) Anion gap (AG)

33
1) pH

pH is the negative logarithm (-log) of [H+]
in a solution. [H+]=40nmol/L (pH=7.4)

The normal range in artery blood =7.35~7.45 (7.41)

The survival range of pH=6.8~7.8

According to the Henderson-Hasselbalch
equation:
The pKa is the dissociation constant of carbonic acid (=6.1)
34
24 [HCO3 ¯ ] metabolic factor
pH =6.1+ log --------------------------------------1.2 [H2CO3] respiratory factors
20
= 6.1+ log---------- =6.1+1.3=7.4
1
The pH is determined by the ratio of
[HCO3¯ ]
20
--------------=--------[H2CO3]
1
No matter how the absolute amounts of HCO3¯ and
H2CO3 change, once the ratio remains 20/1, the pH would
be 7.4 (normal).
35
24 [HCO3 ¯ ] metabolic factor
pH =6.1+ log --------------------------------------1.2 [H2CO3] respiratory factors
The primary changes determines the
nature of the acid-base imbalance.

The purpose of secondary change is
to restore the pH.

According to the pH:
 compensatory acid-base disturbances
 decompensatory acid-base disturbances

36
Clinical significance
(anticoagulant artery blood, insulation of air)
A normal range of pH may represent
three different situations:
① acid-base balance;
② compensatory acidosis or alkalosis;
(causes??)
③ a mixed decompensatory acidosis and
decompensatory alkalosis.
37
(教材106页表下一段有错）
pH<7.35 decompensatory acidosis
acidemia (causes??)
pH>7.45 decompensatory alkalosis
alkalemia (causes??)
38
2) PaCO2
CO2 in blood:
(a) 23% HbCO2 in RBC
(b) 70% HCO3- in plasma
(c) 7% CO2 molecule in plasma
PaCO2 is the tension of CO2 caused by CO2
molecule movement.
The normal range = 33~46(40) mmHg
(4.39~6.25 kPa).
PaCO2 is almost equal to PACO2.
39
The capability of normal lung to
eliminate CO2 is very good. CO2 retention will
not occur with normal ventilation. Generally
speaking, the PaCO2 is determined mainly by
the respiration, so the PaCO2 is called the
“respiratory factor”.
Higher PaCO2 is due to the inhibition of
respiration.
Lower PaCO2 is due to overventilation.
40
Significance
PaCO2>46mmHg
Primary increase: respiratory acidosis
Secodary increase: metabolic alkalosis
(compensated by lung)
PaCO2<33mmHg
Primary decrease: respiratory alkalosis
Secodary decrease: metabolic acidosis
(compensated by lung)
Normal PaCO2 means ???
41
3) Actual bicarbonate (AB)
Standard bicarbonate (SB),
The normal [HCO3¯ ] is 22~27(24)
mmol/L.
AB is measured under “actual condition”
in which both respiratory factor and
metabolic factor affected the [HCO3¯ ].
CO2 +H2O=H2CO3=H++HCO3 ¯
42
SB is measured under “standard condition”
(temperature 37~38℃, full oxygenation of
hemoglobin, PaCO2 = 40 mmHg). Standard
condition means that the respiratory factor
is eliminated, then the [HCO3¯ ] is only
affected by metabolic factor.
Higher SB means metabolic alkalosis or
respiratory acidosis compensated by kidneys.
Low SB means metabolic acidosis or
respiratory alkalosis compensated by kidneys.
43
Normally the AB=SB.
If AB>SB (CO2 retention), the reason
must be the effect of respiratory factor,
which indicates respiratory acidosis or
metabolic alkalosis compensated by lung.
44

If AB<SB (CO2 depletion), the
reason must be the respiratory factor,
which means respiratory alkalosis or the
metabolic acidosis compensated by lung.

CO2 +H2O=H2CO3=H++HCO3-
45
4) Buffer base (BB)
Sum of all buffer basees in blood
 In plasma: HCO3 ¯ =24

Protein¯ =17
 In RBC:
Hb¯

HbO2¯ =6.3

HPO4 2¯ =1.0
 BB=45~55 mmol/L
 Determined by metabolic factors

46
Significance
Normal BB:
acid-base balance
metabolic acidosis + metabolic alkalosis
Increased BB:
metabolic alkalosis
Decreased BB:
metabolic acidosis
47
5) Base excess (BE)
Under “standard condition” (temperature 37~38℃, full
oxygenation of hemoglobin, PaCO2 = 40 mmHg), titrate the
whole blood to pH7.4 with how much acid or base (mmol/L).
If with acid, there is must more base (excess) in the
blood, BE is expressed with positive value
If with base, there is must more acid (deficit) in the
blood, BE is expressed with negative value
Normal BE= -3.0~+3.0
the BE.
Only metabolis factor determines
In metabolic alkalosis the positive BE increases.
In metabolic acidosis the negative BE increases.
48
6) Anion gap (AG)
AG=UA-UC
Determined
cation
Na+
Cl －
Determined
anion
HCO3 －
undetermined
cations
UC
UA
undetermined
anions
49
The AG can be
calculated by:
UA+ HCO3¯ + Cl¯
=UC+Na+
UA-UC=Na+-(Cl¯ +
HCO3¯ )
The normal range
is 10~14 mmol/L.
AG indicates those
anions, other than
HCO3¯ and Cl¯, which
is required to counterbalance Na+.
Na+
Cl －
HCO3
UC
－
AG
UA
50
Actually the AG represents the
proteins with negative charge, phosphate,
sulfate and organic anions (lactic acid,
keto-acid, etc.).

An increased AG is the same
meaning
as
the
accumulation
of
nonvolatile acids in the body and must be
the metabolic acidosis.

51
Significance
(a) For the classification of metabolic acidosis
a)metabolic acidosis with normal AG ( with
increased Cl ¯ ) and
b) metabolic acidosis with high AG (with
normal Cl ¯).
(b) Diagnosis of mixed acid-base imbalances
52
Reported by special instrument with
expensive reagents.
CO2CP indicates the [HCO3¯ ] in
venous blood sample under “actual
condition”, that can be measured easily
without expensive instrument.
53