AcidAcid :: Proton (HProton (H
++
) donor ) donor e.g. e.g. HCl, HHCl, H
22SOSO
44
BaseBase :: Proton acceptor Proton acceptor e.g. e.g. ClCl
--
, HCO, HCO
33
--
Conjugate baseConjugate base :: Acid after proton release. Acid after proton release.
HH
22COCO
33 HCO HCO
33
--
+ H + H
++
Conjugate baseConjugate base
Acidity Acidity
State of HState of H
++
concentration of a solution. concentration of a solution.
Directly proportional to acid content. Directly proportional to acid content.
Indirectly proportional to base / alkali content. Indirectly proportional to base / alkali content.
Expression of Acidity Expression of Acidity
1. Arithmetic scale1. Arithmetic scale
Measure HMeasure H
++
concentration in absolute unit. concentration in absolute unit.
e.g.e.g. 10 10
-3-3
mol/L or 0.001 mol/L mol/L or 0.001 mol/L
2. Logarithmic scale (pH scale)2. Logarithmic scale (pH scale)
Measure acidity by anti-log of HMeasure acidity by anti-log of H
++
conc. conc.
pHpH
Negative log of HNegative log of H
++
conc.; when conc. expressed in mol/L conc.; when conc. expressed in mol/L
If HIf H
++
conc. = 10 conc. = 10
-3-3
mol/L; pH = -log 10 mol/L; pH = -log 10
-3-3
= 3 = 3
If HIf H
++
conc. = 10 conc. = 10
-7-7
mol/L; pH = -log 10 mol/L; pH = -log 10
-7-7
= 7 = 7
pH & HpH & H
++
conc. of Solution conc. of Solution
Inversely relatedInversely related
One unit rise of pH causes 10 times fall of HOne unit rise of pH causes 10 times fall of H
++
One unit fall of pH causes 10 times rise of HOne unit fall of pH causes 10 times rise of H
++
pH & HpH & H
++
conc. of H conc. of H
22OO
pH = 7pH = 7
HH
++
conc. conc. = 10= 10
-7-7
mol/L mol/L
= 10= 10
-7-7
× 10 × 10
99
nmol/L = 100 nmol/L nmol/L = 100 nmol/L
Acidity of Body Fluid Acidity of Body Fluid
In logarithmic scale
(pH)
In arithmetic scale
(H
+
conc. in
nmol/L)
6.8 160
7.3 50
7.35 45
7.4 40
7.45 35
7.5 30
7.8 16
Normal : 7.35 to 7.45
Clinically safe : 7.3 to 7.5
Compatible to life: 6.8 to 7.8
Contd…
6.8 7.8
7.35 7.45
Acidosis
(Acidemia)
Alkalosis
(Alkalemia)
Proton deficitProton excess
Normal
Death
Death
Contd…
ICF
7.0 – 7.3
ECF
7.35 – 7.45
Built-in by Almighty
Make me happy
I will give you haven
Metabolic Acids & BasesMetabolic Acids & Bases
Acid / base Daily production
Volatile acid (CO
2) 15 – 20 mol
Non volatile acid 230 mmol
Non volatile base 160 mmol
The net account:The net account: Net acid producer Net acid producer
1. Volatile acid : 15 – 20 mol/d
2. Non volatile acid: 70 (50-100) mmol/d
Source of Volatile AcidSource of Volatile Acid
•Complete oxidation of glucoseComplete oxidation of glucose
•Complete oxidation of fatty acid Complete oxidation of fatty acid
•Oxidation of amino acidOxidation of amino acid
Source of Non Volatile AcidSource of Non Volatile Acid
•In complete oxidation of glucose & fatty acid In complete oxidation of glucose & fatty acid
•Oxidation of amino acid (basic & sulfur)Oxidation of amino acid (basic & sulfur)
•Oxidation of phosphate containing substance Oxidation of phosphate containing substance
Source of Non Volatile BaseSource of Non Volatile Base
•Oxidation of amino acid (acidic)Oxidation of amino acid (acidic)
•Salts of organic acid of fruits & vegetables Salts of organic acid of fruits & vegetables
Acid Base Disposal (routes) Acid Base Disposal (routes)
Acid / base Route of disposal
Volatile acid Pulmonary route
Non volatile acid Renal route
Base Renal route
Contd…
Defense of Body Fluid pHDefense of Body Fluid pH
1. Body buffer system1. Body buffer system :: Act within second to minutes Act within second to minutes
2. Pulmonary system2. Pulmonary system:: Act within minute to hoursAct within minute to hours
3. Renal system3. Renal system :: Act within hours days Act within hours days
Buffer System Buffer System
Mixture of weak acid Mixture of weak acid (HB) (HB) & its conjugate base & its conjugate base (B(B
--
))
Prevent marked change of pH (HPrevent marked change of pH (H
++
conc.) of solution conc.) of solution
Acid component donate proton (HAcid component donate proton (H
++
) in proton deficit) in proton deficit
Base component take up proton (HBase component take up proton (H
++
) in proton excess ) in proton excess
Body Buffer System Body Buffer System
Buffer system Weak acid Conjugate base
Bicarbonate
HCO
3
-
/ H
2
CO
3
H
2
CO
3
(carbonic acid)
HCO
3
-
(bicarbonate ion)
Phosphate
PO
4
-2
/ H
2
PO
4
-
H
2
PO
4
-
Buffering Activity Buffering Activity
In proton deficit (alkalosis): In proton deficit (alkalosis):
HH
22COCO
33 (HB) (HB) HCO HCO
33
--
(B (B
--
))
HH
++
Acid releases proton & converted to conjugate baseAcid releases proton & converted to conjugate base
Acid conc. (HB or HAcid conc. (HB or H
22COCO
33) decreases) decreases
Base conc. (BBase conc. (B
--
or HCO or HCO
33
--
) increases ) increases
Proton (HProton (H
++
) conc. & pH near normal) conc. & pH near normal
Contd…Contd…
In proton excess (acidosis): In proton excess (acidosis):
HCOHCO
33
--
(B (B
--
) ) H H
22COCO
33 (HB) (HB)
HH
++
Base take up proton & converted to weak acidBase take up proton & converted to weak acid
Acid conc. (HB or HAcid conc. (HB or H
22COCO
33) increases) increases
Base conc. (BBase conc. (B
--
or HCO3 or HCO3
--
) decreases ) decreases
Proton (HProton (H
++
) conc. & pH near normal ) conc. & pH near normal
Contd…Contd…
Response of HCOResponse of HCO
33 Buffer Buffer
1. In acidosis: 1. In acidosis:
2. In alkalosis:2. In alkalosis:
32
-
3
COH
HCO
32
-
3
COH
HCO
Base Excretion Base Excretion
Renal HCORenal HCO
33
--
Reabsorption / Excretion (PCT) Reabsorption / Excretion (PCT)
H
+
H
+
HCO
3
-
H
2
CO
3
CO
2
H
2O
CO
2
+ H
2
O
H
2
CO
3 HCO
3
-
HCO
3
-
LUMEN CELL BLOOD
Acid Excretion Acid Excretion
Renal acid excretion & HCORenal acid excretion & HCO
33 generation (DCT) generation (DCT)
H
+ H
+
CO
2
+ H
2
O
H
2
CO
3 HCO
3
-
HCO
3
-
LUMEN CELL BLOOD
HPO
4
-2
, NH
3
H
2
PO
4
-
, NH
4
+
H
+ H
+
Excretion
HCO
3
-
+ H
+
H
2
CO
3
CO
2
+ H
2
O
pH depends on plasma HCOpH depends on plasma HCO
33
--
conc. conc.
pH depends on plasma HpH depends on plasma H
22COCO
33 conc. conc.
pH depends on plasma HCOpH depends on plasma HCO
33
--
/ H / H
22COCO
33 ratio. ratio.
Single best answer ??? Single best answer ???
Normal HCONormal HCO
33
--
/ H / H
22COCO
33 ratio = 20:1 ratio = 20:1
If the ratio is 20; body pH will be normal (7.4) irrespective If the ratio is 20; body pH will be normal (7.4) irrespective
of plasma HCOof plasma HCO
33
--
conc. & H conc. & H
22COCO
33 conc. conc.
Bicarbonate Buffer Bicarbonate Buffer
PCOPCO
22 dCOdCO
22 H H
22COCO
33 HCO HCO
33
--
+ H+ H
++
Total COTotal CO
22 (TCO (TCO
22))
TCOTCO
22 = 28 mmol/L, HCO = 28 mmol/L, HCO
33
--
= 25 mmol/L = 25 mmol/L
95% of TCO95% of TCO
22 is HCO is HCO
33
--
Interpretation of TCOInterpretation of TCO
22 & HCO & HCO
33
--
is identical. is identical.
Standard HCOStandard HCO
3 3 : 25 mmol/L: 25 mmol/L
It is the plasma HCOIt is the plasma HCO
33
--
conc. at conc. at
Body temperature 37°CBody temperature 37°C
Arterial PCOArterial PCO
22 40 mmHg 40 mmHg
Hb conc. normal (14-16 g/dl)Hb conc. normal (14-16 g/dl)
Oxygen saturation of Hb normal (>95%)Oxygen saturation of Hb normal (>95%)
Base Excess (BE)Base Excess (BE)
Difference between present HCODifference between present HCO
33
--
& standard HCO & standard HCO
33
--
BE = [HCOBE = [HCO
33
--
]]
pp – [HCO – [HCO
33
--
]]
stdstd
(-2 to +2 mmol/L) (-2 to +2 mmol/L)
Positive BE: Positive BE: Present HCOPresent HCO
33
--
> standard HCO > standard HCO
33
--
e.g. e.g. metabolic alkalosismetabolic alkalosis
Negative BE:Negative BE: Present HCO Present HCO
33
--
< standard HCO < standard HCO
33
--
e.g. e.g. metabolic acidosismetabolic acidosis
Classification of Acid Base Disorder (ABD)Classification of Acid Base Disorder (ABD)
32
-
3
COH
HCO
log1.6pH
2
-
3
PCO 0.03
HCO
log1.6pH
2
-
3
PCO
HCO
pH
Contd…Contd…
2
-
3
PCO
HCO
pH
1. Simple ABD:1. Simple ABD: either HCO either HCO
33 or PCO or PCO
22 abnormal abnormal
•Metabolic ABD: Metabolic ABD:
abnormal HCOabnormal HCO
33 with normal PCO with normal PCO
22
•Respiratory ABD: Respiratory ABD:
abnormal PCOabnormal PCO
22 with normal with normal
HCOHCO
33
2. Mixed (complex) ABD:2. Mixed (complex) ABD: both HCO both HCO
33 & PCO & PCO
22 abnormal abnormal
different combination of simple ABDdifferent combination of simple ABD
Contd…Contd…
Types of Metabolic ABDTypes of Metabolic ABD
1. Metabolic acidosis:1. Metabolic acidosis: ↓ HCO ↓ HCO
33 but PCO but PCO
22 normal normal
2. Metabolic alkalosis:2. Metabolic alkalosis: ↑ HCO ↑ HCO
33 but PCO but PCO
22 normal normal
Contd…Contd…
2
-
3
PCO
HCO
pH
2
-
3
PCO
HCO
pH
Types of Respiratory ABDTypes of Respiratory ABD
1. Respiratory acidosis:1. Respiratory acidosis: ↑ PCO ↑ PCO
22 but but
HCOHCO
33 normal normal
2. Respiratory alkalosis:2. Respiratory alkalosis: ↓ PCO ↓ PCO
22 but but
HCOHCO
33 normal normal
2
-
3
PCO
HCO
pH
2
-
3
PCO
HCO
pH
Simple ABD (Gimpses)Simple ABD (Gimpses)
Simple ADB
Primary
event
Unaffected
component
HCO
3
-
/
PCO
2
ratio
pH
M. acidosis ↓ HCO
3
-
PCO
2 ↓ ↓
M. alkalosis↑ HCO
3
-
PCO
2 ↑ ↑
R. acidosis ↑ PCO
2 HCO
3
-
↓ ↓
R. alkalosis↓ PCO
2 HCO
3 ↑ ↑
Compensation of ABDCompensation of ABD
Follows the primary event of HCOFollows the primary event of HCO
33 or PCO or PCO
22
Second unaffected component (HCOSecond unaffected component (HCO
33 or PCO or PCO
22) changes ) changes
in the direction of primary eventin the direction of primary event
Tends to bring HCOTends to bring HCO
33 / PCO / PCO
22 ratio & pH near normal ratio & pH near normal
Metabolic ABD are compensated by respiratory systemMetabolic ABD are compensated by respiratory system
Respiratory ABD are compensated by renal systemRespiratory ABD are compensated by renal system
Contd…Contd…
ABD Compensation
Type Defect Mechanism Response Extent
M. acidosisHCO
3
↓Hyperventi.PCO
2
↓Large
M. alkalosis HCO
3
↑ Hypoventi. PCO
2
↑ Modest
R. acidosisPCO
2 ↑Renal HCO
3
generation
HCO
3 ↑Modest
R. alkalosis PCO
2
↓ Renal HCO
3
excretion
HCO
3
↓ Large
Contd…Contd…
ABD Scale of compensation Max. limit
M. acido. ∆ PCO
2 = 1.2 ∆ HCO
3 PCO
2 ↓ by 1.2 for
1 unit HCO
3 ↓
PCO
2 not
<10
M. alkalo.∆ PCO
2
= 0.5 ∆ HCO
3
PCO
2
↑ by 0.5 for
1 unit HCO
3 ↑
PCO
2
not
>60
R. acido. ∆ HCO
3
-
= 0.35 ∆ PCO
2 HCO
3 ↑ by 0.35 for
1 unit PCO
2
↑
HCO
3 not
>40
R. alkalo. ∆ HCO
3
-
= 0.5 ∆ PCO
2HCO
3 ↓ by 0.5 for
1 unit PCO
2 ↓
HCO
3 not
<15
Effect of ABD on Bicarbonate Buffer Effect of ABD on Bicarbonate Buffer
PCO
2
dCO
2
H
2
CO
3
HCO
3
-
+ H
+
ABD 1
0
event2
0
event pH Plasma
HCO
3
-
M. acido. HCO
3
-
PCO
2
Near
normal
M. alkalo. HCO
3
-
PCO
2
Near
normal
R. acido. PCO
2
HCO
3
-
Near
normal
R. alkalo. PCO
2 HCO
3
-
Near
normal
2
-
3
PCO
HCO
pH
Outcome of Compensation Outcome of Compensation
Near normal pH Near normal pH
(still in the direction of primary event)(still in the direction of primary event)
Abnormal serum bicarbonate:Abnormal serum bicarbonate:
High bicarbonate in M. alkalosis & R. acidosisHigh bicarbonate in M. alkalosis & R. acidosis
Low bicarbonate in M. acidosis & R. alkalosis. Low bicarbonate in M. acidosis & R. alkalosis.
Correction Correction
Normalization of serum bicarbonate.Normalization of serum bicarbonate.
Done by kidney following treatment of the cause. Done by kidney following treatment of the cause.
ABD HCO
3 Correction
M. acidosis HCO
3
generation
M. alkalosis HCO
3
excretion
R. acidosis HCO
3
excretion
R. alkalosis HCO
3
reabsorption
Acid Base Parameter Acid Base Parameter
Parameter Normal value
(arterial blood)
Significance
pH 7.35 – 7.45 Confirmatory
PCO
2
40 mmHg (35 – 45) Confirmatory
HCO
3
25 mmol/L (22 - 28) Confirmatory
BE
- 2 to + 2 meq/L Confirmatory
Anion gap
10 – 20 meq/L Suggestive
Data Interpretation (steps)Data Interpretation (steps)
Step-1:Step-1: Evaluation of pH change Evaluation of pH change
It determines acidosis or alkalosisIt determines acidosis or alkalosis
Step-2: Step-2: Evaluation of HCOEvaluation of HCO
33
--
change change
If compatible with pH → primary eventIf compatible with pH → primary event
If not compatible with pH → compensatory event If not compatible with pH → compensatory event
Step-3: Step-3: Evaluation of PCOEvaluation of PCO
22
If compatible with pH → primary eventIf compatible with pH → primary event
If not compatible with pH → compensatory event If not compatible with pH → compensatory event
Contd…Contd…
Problem-1Problem-1
pH pH = 7.3 = 7.3
HCOHCO
33 = 16= 16
PCOPCO
22 = 30= 30
Step-1:Step-1: Acidosis Acidosis
Step-2:Step-2: Decreased HCO Decreased HCO
33 compatible with decreased pH compatible with decreased pH
So metabolic acidosis So metabolic acidosis
Step-3:Step-3: Decreased PCODecreased PCO
22 not compatible with decreased pH not compatible with decreased pH
So not respiratory acidosis So not respiratory acidosis
Final diagnosis:Final diagnosis: Compensated metabolic acidosis Compensated metabolic acidosis
Simple Way of Data Interpretation Simple Way of Data Interpretation
pH HCO
3
PCO
2
Diagnosis
Decreased Decreased Decreased M. acidosis
Increased Increased Increased M. alkalosis
Decreased Increased Increased R. acidosis
Increased Decreased Decreased R. alkalosis
Contd…Contd…
Complex ABDComplex ABD
1. If 21. If 2
ndnd
(unaffected) component changes in opposite. (unaffected) component changes in opposite.
M. acido + R. acidoM. acido + R. acido
2. If 22. If 2
ndnd
(unaffected) component remain normal. (unaffected) component remain normal.
M. acido + R. acidoM. acido + R. acido
3. Over compensation.3. Over compensation.
R. acido + M. alkaloR. acido + M. alkalo
4. Under compensation.4. Under compensation.
R. alkalo + M. alkaloR. alkalo + M. alkalo
5. Normal pH but abnormal PCO5. Normal pH but abnormal PCO
22 & / or HCO & / or HCO
33..
e.g. e.g. M. acidosis + R. alkalosisM. acidosis + R. alkalosis
M. alkalosis + R. acidosis M. alkalosis + R. acidosis
6. Clinical features of ABD but normal pH, PCO6. Clinical features of ABD but normal pH, PCO
22, HCO, HCO
33..
e.g. e.g. M. acidosis + M. alkalosisM. acidosis + M. alkalosis
Some Tips Some Tips
1. HCO1. HCO
33 < 10 meq/L. < 10 meq/L.
M. acidosis is likely. R. alkalosis is unlikelyM. acidosis is likely. R. alkalosis is unlikely
2. HCO2. HCO
33 > 40 meq/L. > 40 meq/L.
M. alkalosis is likely. R. acidosis is unlikelyM. alkalosis is likely. R. acidosis is unlikely
3. Plasma anion gap: 20 to 30 meq/L.3. Plasma anion gap: 20 to 30 meq/L.
M. acidosis is likely.M. acidosis is likely.
4. Plasma anion gap >30 meq/L.4. Plasma anion gap >30 meq/L.
M. acidosis confirm. M. acidosis confirm.
Contd…Contd…
5. If HCO5. If HCO
33 & PCO & PCO
22 changes in same direction: changes in same direction:
simple ABD is most likely simple ABD is most likely
6. If HCO6. If HCO
33 & PCO & PCO
22 changes in opposite direction: changes in opposite direction:
complex ABD is definitecomplex ABD is definite
7. If PCO7. If PCO
22 is higher than expected for respiratory is higher than expected for respiratory
compensation in metabolic ABD:compensation in metabolic ABD:
R. acidosis coexist R. acidosis coexist
Contd…Contd…
8. If PCO8. If PCO
22 is lower than expected for respiratory is lower than expected for respiratory
compensation in metabolic ABD:compensation in metabolic ABD:
R. alkalosis coexist R. alkalosis coexist
9. If HCO9. If HCO
33 is higher than expected for renal is higher than expected for renal
compensation in respiratory ABD:compensation in respiratory ABD:
M. alkalosis coexist M. alkalosis coexist
10. If HCO10. If HCO
33 is lower than expected for renal is lower than expected for renal
compensation in respiratory ABD: compensation in respiratory ABD:
M. acidosis coexistM. acidosis coexist
Anion GapAnion Gap
In plasma: Total cation = Total anion.In plasma: Total cation = Total anion.
NaNa
++
+ K + K
++
+ UC = Cl + UC = Cl
--
+ HCO + HCO
33
--
+ UA. + UA.
(Na(Na
++
+ K + K
++
) – (Cl) – (Cl
--
+ HCO + HCO
33
--
) = UA-UC.) = UA-UC.
So, anion gap So, anion gap
= (Na= (Na
++
+ K + K
++
) – (Cl) – (Cl
--
+ HCO + HCO
33
--
))
OROR
= UA = UA (unmeasured anion)(unmeasured anion) – UC – UC (unmeasured cation)(unmeasured cation)..
Normal anion gap Normal anion gap = 10 – 20 meq/L. = 10 – 20 meq/L.
Contd…Contd…
Common unmeasured anion: Common unmeasured anion:
Albumin, phosphate, sulfate, lactate, Albumin, phosphate, sulfate, lactate,
keto acid anion, weak organic acid anion etc. keto acid anion, weak organic acid anion etc.
Common unmeasured cation:Common unmeasured cation:
Calcium, magnesium, γ-globulin etc. Calcium, magnesium, γ-globulin etc.
Contd…Contd…
Causes of Increased Anion Gap Causes of Increased Anion Gap
Renal failure.Renal failure.
Lactic acidosis.Lactic acidosis.
Ketoacidosis.Ketoacidosis.
Intoxication (poisoning).Intoxication (poisoning).
Alkalosis. Alkalosis.
modestly affect modestly affect (not by > 6 (not by > 6
meq/L)meq/L)
Contd…Contd…
Importance of Anion GapImportance of Anion Gap
1. Determine etiology of metabolic acidosis.1. Determine etiology of metabolic acidosis.
a) high anion gap variety e.g. CRF, LA, KA etc.a) high anion gap variety e.g. CRF, LA, KA etc.
b) normal anion gap variety e.g. diarrhea, RTA.b) normal anion gap variety e.g. diarrhea, RTA.
2. Diagnose ABD in critical scenario when pH, PCO2. Diagnose ABD in critical scenario when pH, PCO
22, ,
HCO HCO
33 found normal. found normal.
e.g. M. alkalosis + lactic acidosis e.g. M. alkalosis + lactic acidosis
Contd…Contd…
3. Differentiate between simple & complex ABD.3. Differentiate between simple & complex ABD.
a) simple high anion gap M. acidosis.a) simple high anion gap M. acidosis.
b) simple normal anion gap M. acidosis. b) simple normal anion gap M. acidosis.
* AG = (Na* AG = (Na
++
+ K + K
++
) – (Cl) – (Cl
--
+ + ↓↓HCOHCO
33
--
))
1
HCO
AG
3
0
HCO
AG
3
Contd…Contd…
c) M. acidosis + other ABD.c) M. acidosis + other ABD.
* AG = (Na* AG = (Na
++
+ K + K
++
) – (Cl) – (Cl
--
+ + ↓↓HCOHCO
33
--
))
* If >1: high AG M. acidosis + M. alkalosis* If >1: high AG M. acidosis + M. alkalosis
* If between 0 to 1 (<1): normal & high AG M. acidosis * If between 0 to 1 (<1): normal & high AG M. acidosis
1or 10between
HCO Δ
AG Δ
3