ACID-BASE BALANCE

Editor:
dr. Husnil Kadri, MKes

Biochemistry Departement
Medical Faculty Of Andalas University
Padang
 Acid-Base Balance
Normal pH of body fluids
Arterial blood is 7.4
Venous blood and interstitial fluid is 7.35
Intracellular fluid is 7.0
Alkalosis or alkalemia arterial blood pH
rises above 7.45
Acidosis or acidemia arterial pH drops
below 7.35
2
 Sources of Hydrogen Ions
Most hydrogen ions originate from cellular
metabolism
Breakdown of phosphorus-containing proteins
releases phosphoric acid into the ECF
Anaerobic respiration of glucose produces
lactic acid
Fat metabolism yields organic acids and
ketone bodies
Transporting carbon dioxide as bicarbonate
releases hydrogen ions 3
Acid/Base Homeostasis: Overview

4
 Hydrogen Ion Regulation
Concentration of hydrogen ions is
regulated sequentially by:
Chemical buffer systems act within seconds
The respiratory center in the brain stem acts
within 1-3 minutes
Renal mechanisms require hours to days to
effect pH changes

5
 Chemical Buffer Systems
One or two molecules that act to resist pH
changes when strong acid or base is
added
Three major chemical buffer systems
Bicarbonate buffer system
Phosphate buffer system
Protein buffer system

6
 1. Bicarbonate Buffer System
A mixture of carbonic acid (H2CO3) and its
salt, sodium bicarbonate (NaHCO3)
(potassium or magnesium bicarbonates
work as well)
If strong acid is added:
Hydrogen ions released combine with the
bicarbonate ions and form carbonic acid (a
weak acid)
The pH of the solution decreases only slightly
7
 Bicarbonate Buffer System
If strong base is added:
It reacts with the carbonic acid to form sodium
bicarbonate (a weak base)
The pH of the solution rises only slightly
This system is the only important ECF
buffer

8
 2. Phosphate Buffer System
Nearly identical to the bicarbonate system
Its components are:
Sodium salts of dihydrogen phosphate
(H2PO4), a weak acid
Monohydrogen phosphate (HPO42), a weak
base
This system is an effective buffer in urine
and intracellular fluid

9
 3. Protein Buffer System

Plasma and intracellular proteins are the

bodys most plentiful and powerful buffers
Some amino acids of proteins have:
Free organic acid groups (weak acids)
Groups that act as weak bases (e.g., amino
groups)

10
 Buffer Systems

The respiratory system regulation of acid-

base balance is a physiological buffering
system

There is a reversible equilibrium:

CO2 + H2O H2CO3 H+ + HCO3

11
 Buffer Systems

When hypercapnia or rising plasma H+

occurs:
Deeper and more rapid breathing expels more
carbon dioxide
Hydrogen ion concentration is reduced
Alkalosis causes slower, more shallow
breathing, causing H+ to increase

12
 Renal Mechanisms of Acid-Base
Balance
Chemical buffers can tie up excess acids
or bases, but they cannot eliminate them
from the body
The lungs can eliminate carbonic acid by
eliminating carbon dioxide
Only the kidneys can rid the body of
metabolic acids (phosphoric, uric, and
lactic acids and ketones) and prevent
metabolic acidosis
13
 Renal Mechanisms of
Acid-Base Balance
The most important renal mechanisms for
regulating acid-base balance are:
Conserving (reabsorbing) or generating new
bicarbonate ions
Excreting bicarbonate ions
Losing a bicarbonate ion is the same as
gaining a hydrogen ion; reabsorbing a
bicarbonate ion is the same as losing a
hydrogen ion
14
Kidney Hydrogen Ion Balancing:
Proximal Tubule

15
Figure 20-21: Proximal tubule secretion and reabsorption of filtered HCO3-
Reabsorption of Bicarbonate

16
Hydrogen Ion Excretion

17
 Ammonium Ion Excretion
This method uses ammonium ions
produced by the metabolism of glutamine
in PCT cells
Each glutamine metabolized produces two
ammonium ions and two bicarbonate ions
Bicarbonate moves to the blood and
ammonium ions are excreted in urine

18
Ammonium Ion Excretion

19
 Bicarbonate Ion Secretion
When the body is in alkalosis, type B
intercalated cells:
Exhibit bicarbonate ion secretion
Reclaim hydrogen ions and acidify the blood
The mechanism is the opposite of type A
intercalated cells and the bicarbonate ion
reabsorption process
Even during alkalosis, the nephrons and
collecting ducts excrete fewer bicarbonate
ions than they conserve
20
Kidney Hydrogen Ion Balancing: Collecting Duct
CARA TRADISIONAL :

Hendersen-Hasselbalch
(1909)

22
 [HCO
BASA3-]
HCO
Normal
GINJAL HCO 3
3

pH = 6.1 + log Kompensasi

Normal PARU
pCO2
ASAM CO
CO22

23
Carbonic acid/bicarbonate buffer system
pKa = 6.1
ECF: H2CO3 H+ + HCO3-
Carbonic acid Bicarbonate ion

The pKa of carbonic acid is 6.1

Carbonic acid is the major buffer in ECF
The pH of blood can be determined using
the Henderson-Hasselbalch equation

24
 Henderson-Hasselbalch equation
pH = pKa + log [HCO3-]/[H2CO3]

pH = pKa + log [HCO3-]/0.03 x PCO2

7.4 = 6.1 + log 20 / 1

7.4 = 6.1 + 1.3

Plasma pH equals 7.4 when buffer ratio is 20/1

The solubility constant of CO2 is 0.03
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 GANGGUAN KESEIMBANGAN ASAM-BASA
TRADISIONAL

DISORDER pH PRIMER RESPON

KOMPENSASI

ASIDOSIS HCO3- pCO2

METABOLIK

ALKALOSIS HCO3- pCO2

METABOLIK

ASIDOSIS pCO2 HCO3-

RESPIRATORI

ALKALOSIS pCO2 HCO3-

RESPIRATORI
Normal Compensatory Response
Any primary disturbance in acid-base
homeostasis invokes a normal
compensatory response.
A primary metabolic disorder leads to
respiratory compensation, and a primary
respiratory disorder leads to an acute
metabolic response due to the buffering
capacity of body fluids.
A more chronic compensation (1-2 days) due
to alterations in renal function.
 Mixed Acid - Base Disorder
Most acid-base disorders result from a single primary
disturbance with the normal physiologic compensatory
response and are called simple acid-base disorders.

In certain cases, however, particularly in seriously ill

patients, two or more different primary disorders may
occur simultaneously, resulting in a mixed acid-base
disorder.

The net effect of mixed disorders may be additive (eg,

metabolic acidosis and respiratory acidosis) and result
in extreme alteration of pH;

or they may be opposite (eg, metabolic acidosis and

respiratory alkalosis) and nullify each others effects on
the pH.
Cara Stewart ;
pH atau [H+] DALAM PLASMA
DITENTUKAN OLEH

DUA VARIABEL

VARIABEL VARIABEL
INDEPENDEN DEPENDEN

Stewart PA. Can J Physiol Pharmacol 61:1444-1461, 1983.

INDEPENDENT VARIABLES DEPENDENT VARIABLES

Strong Ions
Difference

pCO2
pH

Protein
Concentration
 VARIABEL INDEPENDEN

CO2 STRONG ION DIFFERENCE WEAK ACID

pCO2 SID Atot

 DEPENDENT VARIABLES

H+ HCO3-

OH- AH

CO3- A-
 STRONG ION DIFFERENCE

Definisi:
Strong ion difference adalah ketidakseimbangan muatan
dari ion-ion kuat. Lebih rinci lagi, SID adalah jumlah
konsentrasi basa kation kuat dikurangi jumlah dari
konsentrasi asam anion kuat. Untuk definisi ini semua
konsentrasi ion-ion diekspresikan dalam ekuivalensi
(mEq/L).

Semua ion kuat akan terdisosiasi sempurna jika berada didalam

larutan, misalnya ion natrium (Na+), atau klorida (Cl-). Karena
selalu berdisosiasi ini maka ion-ion kuat tersebut tidak
berpartisipasi dalam reaksi-reaksi kimia. Perannya dalam kimia
asam basa hanya pada hubungan elektronetraliti.
Strong Ion Difference
Remember, SID = strong cations strong anions. It
indirectly measures weak ions (HCO3 and A-).

SID = HCO3- + A-
[Just for the record, HCO3 + A- was called Buffer Base as far
back as the 1950s SID was invented by Stewart in 1980.]
 STRONG ION DIFFERENCE
Gamblegram
Mg++
Ca++
K+ 4
SID

[Na+] + [K+] + [kation divalen] - [Cl-] - [asam organik kuat-]

Na+
140 Cl-
102

[Na+] + [K+] - [Cl-] = [SID]

140 mEq/L + 4 mEq/L - 102 mEq/L = 34 mEq/L

KATION ANION
SKETSA HUBUNGAN ANTARA SID,H+ DAN OH-

[H+] [OH-]
Konsentrasi [H+]

Asidosis Alkalosis

() SID (+)

Dalam cairan biologis (plasma) dgn suhu 370C, SID hampir

selalu positif, biasanya berkisar 30-40 mEq/Liter
Gamblegram
Mg++
Ca++
K+ 4 HCO3-
24 SID
Weak acid
(Alb-,P-)

Na+
140
Cl-
102

KATION ANION
 APLIKASI

H3O+ = H+ = 40 mEq/L K
Mg HCO3- SID
Ca HCO3 = 24 SID n
3 SID
HCO -
Alb
P
Alb
Laktat/keto=UA
P
Alb
Na P
140 Keto/laktat
Asidosis
hiperkloremi
asidosis
Cl
CL
Cl
115
95
102
Alkalosis
hipokloremi

KATION ANION
KLASIFIKASI GANGGUAN
KESEIMBANGAN ASAM BASA
BERDASARKAN PRINSIP STEWART

Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of metabolic acid-base disturbances in

critically ill patients. Am J Respir Crit Care Med 2000 Dec;162(6):2246-51
KLASIFIKASI
ASIDOSIS ALKALOSIS
I. Respiratori PCO2 PCO2

II. Nonrespiratori (metabolik)

1. Gangguan pd SID

a. Kelebihan / kekurangan air [Na+], SID [Na+], SID

b. Ketidakseimbangan anion
kuat:
i. Kelebihan / kekurangan Cl- [Cl-], SID [Cl-], SID

ii. Ada anion tak terukur [UA-], SID

2. Gangguan pd asam lemah

i. Kadar albumin [Alb] [Alb]

ii. Kadar posphate [Pi] [Pi]

Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of metabolic acid-base disturbances in

critically ill patients. Am J Respir Crit Care Med 2000 Dec;162(6):2246-51
 RESPIRASI METABOLIK

Abnormal Abnormal Abnormal

pCO2 SID Weak acid

Alb PO4-
AIR Anion kuat

Cl- UA-

Alkalosis Turun kekurangan Hipo Turun

Asidosis Meningkat kelebihan Hiper Positif meningkat

Fencl V, Am J Respir Crit Care Med 2000 Dec;162(6):2246-51

KEKURANGAN AIR - WATER DEFICIT
Diuretic
Diabetes Insipidus
Evaporasi

Plasma Plasma

Na+ = 140 mEq/L

Cl- = 102 mEq/L
SID = 38 mEq/L 140/1/2 = 280 mEq/L
102/1/2 = 204 mEq/L
1 liter liter
SID = 76 mEq/L

SID : 38 76 = alkalosis
ALKALOSIS KONTRAKSI
KELEBIHAN AIR - WATER EXCESS

Plasma

1 Liter 140/2 = 70 mEq/L

Na+ = 140 mEq/L H2O 102/2 = 51 mEq/L
Cl- = 102 mEq/L SID = 19 mEq/L
SID = 38 mEq/L 1 liter 2 liter

SID : 38 19 = Acidosis
ASIDOSIS DILUSI
GANGGUAN PD SID:
Pengurangan Cl-

Plasma

Na+ = 140 mEq/L

Cl- = 95 mEq/L
SID = 45 mEq/L 2 liter

SID ALKALOSIS

ALKALOSIS HIPOKLOREMIK
 GANGGUAN PD SID:
Penambahan/akumulasi Cl-

Plasma

Na+ = 140 mEq/L

Cl- = 120 mEq/L
SID = 20 mEq/L 2 liter

SID ASIDOSIS

ASIDOSIS HIPERKLOREMIK
 PLASMA + NaCl 0.9%

Plasma NaCl 0.9%

Na+ = 140 mEq/L Na+ = 154 mEq/L

Cl- = 102 mEq/L Cl- = 154 mEq/L
SID = 38 mEq/L 1 liter SID = 0 mEq/L 1 liter

SID : 38
ASIDOSIS HIPERKLOREMIK AKIBAT
PEMBERIAN LARUTAN Na Cl 0.9%

Plasma

= Na+ = (140+154)/2 mEq/L= 147 mEq/L

Cl- = (102+ 154)/2 mEq/L= 128 mEq/L

SID = 19 mEq/L 2 liter

SID : 19 Asidosis
PLASMA + Larutan RINGER LACTATE

Plasma Ringer laktat

Laktat cepat
dimetabolisme

Cation+ = 137 mEq/L

Na+ = 140 mEq/L Cl- = 109 mEq/L
Cl- = 102 mEq/L Laktat- = 28 mEq/L
SID= 38 mEq/L 1 liter 1 liter
SID = 0 mEq/L

SID : 38
 Normal pH setelah pemberian
RINGER LACTATE

Plasma

= Na+ = (140+137)/2 mEq/L= 139 mEq/L

Cl- = (102+ 109)/2 mEq/L = 105 mEq/L
Laktat- (termetabolisme) = 0 mEq/L 2 liter
SID = 34 mEq/L

SID : 34 lebih alkalosis dibanding jika diberikan

NaCl 0.9%
 MEKANISME PEMBERIAN NA-
BIKARBONAT PADA ASIDOSIS

Plasma;
asidosis Plasma + NaHCO3
hiperkloremik

25 mEq
NaHCO3 HCO3 cepat
Na+ = 140 mEq/L Na+ = 165 mEq/L dimetabolisme
Cl- = 130 mEq/L Cl- = 130 mEq/L
SID =10 mEq/L 1 liter 1.025 SID = 35 mEq/L
liter

SID : 10 35 : Alkalosis, pH kembali normal namun mekanismenya bukan

karena pemberian HCO3- melainkan karena pemberian Na+ tanpa anion kuat yg
tidak dimetabolisme seperti Cl- sehingga SID alkalosis
 UA = Unmeasured Anion:
Laktat, acetoacetate, salisilat, metanol dll.

K K HCO3- SID
HCO3- SID
Keto-

A- A-

Na+ Na+

Cl- Cl-
Lactic/Keto asidosis

Normal Ketosis
 GANGGUAN PD ASAM LEMAH:
Hipo/Hiperalbumin- atau P-

K K K
HCO3 SID
HCO3 SID HCO3 SID
Alb-/P-
Alb-/P- Alb/P

Na Na Asidosis Na Alkalosis
hiperprotein/ hipoalbumin
Cl hiperposfatemi
Cl Cl /hipoposfate
mi

Normal Acidosis Alkalosis

 Anion Gap

Described by Gamble in 1939

Electroneutrality
Na+, Cl-, and HCO3 are measured ions

Na + UC = Cl + HCO3 + UA

UC = Sum of unmeasured cations

UA = Sum of unmeasured anions
 Anion Gap
Unmeasured Cations: Unmeasured Anions:
total 11 mEq/L total 23 mEq/L
Potassium 4 Sulfates 1
Calcium 5 Phosphates 2
Magnesium 2 Albumin 16
Lactic acid 1
Org. acids 3
 Anion Gap

Na + UC = Cl + HCO3 + UA
140 + 11 = 104 + 24 + 23
151 = 151

UA UC = Na - (Cl + HCO3);
Anion Gap = Na - (Cl + HCO3)
Change in Anion Gap vs HCO3
In simple AG Metabolic Acidosis
decrease in plasma bicarbonate = increase in
AG

Anion Gap = 1
HCO3

Helpful in identifying mixed disorders

 If the anion gap is elevated
Then compare the changes from normal between
the anion gap and [HCO3 -].
If the change in the anion gap is greater than the
change in the [HCO3 -] from normal, then a
metabolic alkalosis is present in addition to a gap
metabolic acidosis.
If the change in the anion gap is less than the
change in the [HCO3 -] from normal, then a non
gap metabolic acidosis is present in addition to a
gap metabolic acidosis.
 Anion Gap Acidosis:
Anion gap >12 mEq/L; caused by a
decrease in [HCO3 -]
balanced by an increase in an
unmeasured acid ion from either
endogenous production or exogenous
ingestion (normochloremic acidosis).
 Non anion Gap Acidosis:
Anion gap = 8-12 mmol/L; caused by a
decrease in [HCO3 -] balanced by an
increase in chloride (hyperchloremic
acidosis). Renal tubular acidosis is a type
of non gap acidosis
 Increased Anion Gap
Normal = 8-15
May differ institutionally

Accumulation of organic acids (ketones,

lactate)
Toxic Ingestions
methanol, ethylene glycol, salicylates
Reduced inorganic acid excretion
phosphates, sulfates
Decrease in unmeasured cations
(unusual)
 Increased AG Metabolic Acidosis:
Methanol Lactic Acidosis
Uremia/Renal Has many etiologies
Failure Cyanide, CO, Toluene,
HS
INH, Iron--lactate Poor perfusion
Paraldehyde Ethylene glycol
Salicylates
Methyl salicylate
(Oil of wintergreen)
Mg salicylate

Levraut J et al. Int Care

Med 23:417, 1997
 Increased Anion Gap
Normal = 8-15
May differ institutionally
ion specific electrodes

Accumulation of organic acids (ketones, lactate)

Toxic Ingestions
methanol, ethylene glycol, salicylates
Reduced inorganic acid excretion
phosphates, sulfates
Decrease in unmeasured cations (unusual)
Decreased or Negative Anion Gap
Clin J Am Soc Nephrol 2: 162-174, 2007

Low protein most important

Albumin has many unmeasured negative
charges
Normal anion gap (12) in cachectic person
Indicates anion gap metabolic acidosis
Other etiologies of low AG:
Low K, Mg, Ca, increased globulins (Mult.
Myeloma), I intoxication
Negative AG
more unmeasured cations than unmeasured
anions
Bromide, Iodide, Multiple Myeloma
64
 Respiratory Compensation
for

Metabolic Acidosis: Metabolic Alkalosis:

Occurs rapidly Calculation not as
Hyperventilation accurate
Kussmaul Respirations Hypoventilation
Deep > rapid (high tidal Not Respiratory
volume) Acidosis
Is not Respiratory Alkalosis
Restricted by
hypoxemia
PCO2 seldom > 50-55
 References
1. Achmadi, A., George, YWH., Mustafa, I. Pendekatan Stewart
Dalam Fisiologi Keseimbangan Asam Basa. 2007
2. Beaudoin, D. Electrolytes and ion sensitive electrodes. PPT.
2003.
3. Ivkovic, A ., Dave, R. Renal review. PPT
4. Kersten. Fluid and electrolytes. PPT.
5. Marieb, EN. Fluid, electrolyte, and acid-base balance. PPT.
Pearson Education, Inc. 2004
6. Rashid, FA. Respiratory mechanism in acid-base homeostasis.
PPT. 2005.
7. Silverthorn, DU. Integrative Physiology II: Fluid and Electrolyte
Balance. Chapter 20, part B. Pearson Education, Inc. 2004
8. Smith, SW. Acid-Base Disorders. www.acid-base.com

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