Mine acid base balance1

• Reactions in the body are dependent on maintenance
of a physiological hydrogen ion concentration and
its regulation is called acid–base balance.
• Changes in ventilation, perfusion and infusion of
electrolyte containing solutions, rapidly alter acid–base
balance.

Acid–base chemistry
• Hydrogen ion concentration & pH
• Acids & bases
• Endogenous acid production
• Effect of change in pH
• Compensatory Mechanisms/Regulation of pH
(1) Immediate Chemical buffering
(2) Respiratory compensation
(3) Renal compensatory response
B. Common disturbances
Acidosis
1) Respiratory
2) Metabolic
Alkalosis
C. Diagnosis of acid–base Disorders

ACID–BASE CHEMISTRY
Hydrogen Ion Concentration & pH
Water molecules reversibly dissociate into
H2O↔H+ +OH−
this process is described by the dissociation
constant ------ Kw
Kw=[H+] * [OH−] = 10−14
{Like most dissociation constants, KW is affected by
changes in temperature}
Example: if [H+] = 10–8 nEq/l,
Then,
[OH−] = 10–14 ÷ 10–8
= 10–6 nEq/l.

*****The Law of Mass Action and Equilibrium Constants
Using the Law of Mass Action, which says that for a balanced
chemical equation of the type
in which A, B, C, and D are chemical species and a, b, c, and d
are their stoichiometric coefficients, a constant quantity, known as
the equilibrium constant (K), can be found as:
where the brackets indicate the concentrations

Equilibrium Constant for an Acid-Base Reaction
Using the Law of Mass Action, we can also define an equilibrium
constant for the acid dissociation equilibrium reaction. This
equilibrium constant, known as Ka, is defined by equation
Equilibrium Constant for the Dissociation of Water

pH
• LOG ???
Log3 9 = how to read?
log 3 raised to the power of x equals 9
Log3 9 = x
we know 32=9
so x=2
• Log 1000=?
Log101000=x
x=3

pH= exponent of [ H+] ion
pH= log 1/[ H+] by sorsen
pH= -log[ H+]
Calculated for 1mol/l or 1 Eq/l of [ H+] ion concentration
Eg. pH of a neutral solution?
[neutral solution] concentration=1*10-7
pH=-log[ H+]
=-log{1*10-7}
=- {log1 +log10-7}
= - {0-7}
=7

pH is inversely related to [H+
So,
Increase in pH - H+ ion 
Decrease in pH - H+ ion 
pH of blood
7.35 to 7.45

If you are given
1 mol/l =[H+]
We know pH= -log[ H+]
= -log 1 = 0
Remember,
1 mol/l =1 Eq/l
Now,
Arterial [H+] is normally 40 nEq/L, or 40 × 10–9 mol/L
so,
pH= -log[ H+]
=-{ log 40 +log 10–9}
=-{1.6-9}
= 7.4 which is the normal pH

Hydrogen ion concentrations between 16 and 160 nEq/L
are compatible with life.
What pH is life threatening?
pH < 7.2 or pH > 7.55
Effect of change in pH
disruption of vital cellular enzymatic reactions and physiological
process
• Na+- k+ pump activity  by half when pH rises by one
unit.
1. interferes with tissue oxygenation
2. normal neurological and muscular functioning
• Phosphofructokinase is a glycolytic enzyme 90%
reduction when pH falls by 0.1
• Mitosis is  by 85% if intra cellular pH falls by 0.4

Acids & bases Brönsted– Lowry
Acid -chemical species that can act as a proton H+
donor, e.g carbonic acid
Base -is a species that can act as a proton acceptor
e.g bicarbonate (HCO3)
A strong acid is a substance that readily and almost
irreversibly gives up an H+ and increases [H+],
strong base avidly binds H+ and decreases [H+].
In contrast,
weak acids reversibly donate H+
weak bases reversibly bind H+ less of an effect on [H+]

Endogenous acid production
 From birth till death life is a acidogenic process.
 Body is under a constant obligation to balance
HYDROGEN ION output against intake and
production.
 Our diet contains hydrogen ion in the form of sulphur
containing amino acids, phosphates etc. which is
added to ECF.
 Urine is the sole channel of hydrogen ion excretion.
 This acid formed is of 2 types
VOLATILE ACIDS and NON-VOLATILE ACIDS

Volatile acids – produced by oxidative metabolism
of carbohydrate ,fat, protein.
in the form of  carbonic acid (H2CO3)
It determines the level of CO2 in blood (paCO2)
Excreted  lung as CO2 gas
22,000 mEq volatile acids produced daily

Non volatile acids - (fixed acids) – acids that do not
leave solution.
Once produced, remain in body fluids until eliminated by
kidney
e.g.organic acids
Produced by dietary and engogenous protein catabolism
at the rate of 1mEq/kg

The suffix “-osis” is used here to denote any pathological
process that alters arterial pH.
Acidosis - disease which reduces pH due to either
increase in acid or decrease in alkali
Alkalosis - disease which increases pH due to decrease
in acid or increase in alkali
“-emia” :it is the result of process in blood
Acidemia: acid+ emia(blood)
Ph<7.35
Alkalemia: alkaline + emia(blood)
Ph >7.45

If the disorder primarily affects
[HCO3
–]---metabolic
[PaCO2]---respiratory
When only one pathological process occurs by itself,
the acid–base disorder is considered to be simple
To minimize changes in pH ,body have different
Compensatory Mechanisms

When body is unable to handle,

Compensatory Mechanisms/Regulation of pH
physiological responses to changes in [H+] are
characterized by three phases:
(1)Immediate Chemical buffering
(2)Respiratory compensation
(3)Renal compensatory response (a slower, but more
effective)

That may nearly normalize arterial pH even if the
underlying pathological process remains present.

Acute buffer capacity of the body is
10 mmol/kg hydrogen ion
that means 500 to 700 in an adult person
which is nearly 10 times of daily intake.
So, If oral intake ceases even then hydrogen ion does
not reach lethal level for 7 to 10 days.

1)IMMEDIATE CHEMICAL BUFFERING
 They are the first line of defence against pH shift
 Buffers minimize any change in [H+] by readily
accepting or giving up hydrogen ions.
 Conjugate Pairs & Buffers
 Types Of Buffer System

Conjugate Pairs & Buffers
When the weak acid (HA) is in solution, HA can act as
an acid by donating an H+, and A– can act as a base by
taking up H+.
A– is therefore often referred to as the conjugate base of
HA.
A similar concept can be applied for weak bases.
A weak base B can
B+H+ ↔BH+ = conjugate acid of B.
A buffer is a solution that contains a weak acid
and its conjugate base or a weak base and its conjugate
acid (conjugate pairs).

kept in mind,
• Buffers are most efficient in minimizing changes in the
[H+] of a solution when pH = pK.
• The conjugate pair must be present in significant
quantities in solution to act as an effective buffer.

Types Of Buffer System
 Plasma proteins
 Hemoglobin
 Tissue proteins

LOCATION BUFFERING DONE BY CAPACITY
ECF Proteins
Phosphate
Ammonia
inorganic compounds
¼
IN THE CELLS Bicarbonate(most
important and fast)
Phosphate
Proteins
Hemoglobin
CO2 stores
¾
URINARY
B u f f e r i n g b y l o c a t i o n

• Buffering of the extracellular compartment can also be
accomplished by the exchange of extracellular H+ for
Na+ and Ca2+ ions from bone and by the exchange of
extracellular H+ for intracellular K+.
• Acid loads can demineralize bone and release
alkaline compounds (CaCO3 and CaHPO4).
• Alkaline loads (NaHCO3) increase the deposition of
carbonate in bone.
Up to 50% to 60% of acid loads may ultimately be
buffered by

bone and intracellular buffers. [slower (2–4 h)]

Most body cells constantly generate CO2.
CO2 is 120 L in body and 48ml/100 ml in arterial blood.
CO2 is transported in 3 forms
1. Solution 5% (most important)
2. Bicarbonate 90% (in prescence of carbonic
anhydrase enzyme in RBC ,carbonic acid is
formed)
3. Carb-amino compounds.
Most CO2is converted to carbonic acid (H2CO3), which
dissociates into H+ and a bicarbonate ion

 This system consist of
H2CO3 ( weak acid) and NaHCO3 (strong base)
carbonic acid bicarbonate ion
 HCl + NaHCO3 ==== H2CO3 + NaCl
 H2CO3 ==== H2O + CO2 excreted by lung
 First strong acid is swept for a weak carbonic acid and
then it dissociates to form water and CO2 which is
excreted by lung.

FACTS
• Prevents changes in pH caused by organic acids and
fixed acids in ECF
• Cannot protect ECF from changes in pH that result
from elevated or depressed levels of CO2 itself
• Functions only when respiratory system and
respiratory control centers are working normally
Ability to buffer acids is limited by availability of
bicarbonate ions

pKa (acid dissociation constant)
1. pKa is a number that shows how weak or strong an acid is.
2. The lower the value of pKa, the stronger the acid and the
greater its ability to donate its protons.
A strong acid will have a pKa of less than zero so lower the value
of pKa, the stronger the acid
pKa is the negative log base ten of the Ka value (acid dissociation
constant).

When pH = pKa, the concentration of HA is equal to the
concentration of A−
The buffer region extends over the approximate range pKa ± 2.
Buffering is weak outside the range pKa ± 1.
The relationship between pH and pKa is described by the
Henderson-Hasselbalch equation

Bicarbonate is not an efficient extracellular buffer
Because,
If adjustments are made in the dissociation constant for
the bicarbonate buffer and if the solubility coefficient for
CO2 (0.03 mEq/L) is taken into consideration,
the Henderson–Hasselbalch equation for bicarbonate
can be written as follows:
where pK′ = pKa of bicarbonate =6.1.
and this its pK’ is away from the normal arterial pH of
7.40 by 1.3

BUT it is still important
(1)Bicarbonate (HCO3
–) is present in high concentrations
in extracellular fluid
(2) more importantly, PaCO2 and plasma [HCO3
–] are
closely regulated by the lungs and the kidneys,
respectively.

Disadvantages of bicarbonate buffer system
 It cannot protect ECF from change in pH due to
elevated or depressed level of CO2 so bicarbonate
buffer is effective against metabolic but not
respiratory acid–base disturbances.
 Functions only when respiratory and respiratory
control centers are working properly
 Ability to buffer acids is limited by the availability of
bicarbonate ions

 Most potent buffering system (per molecule)
 Important in buffering pH of ICF and works best at 6.4
optimal pH. Monobasic phosphate dibasic phosphate
 Consist of (HPO4
2-/H2PO4
-) which are two salts,
KH2PO4(monobasic potssium phosphate) [weak acid]
and
K2HPO4(dibasic potssium phosphate) [conjugate base]
When Hydronuim ions are added,then
HPO4
2- + H3O+ H2PO4
- + H2O
When Hydroxyl ions are added,then
H2PO4
- + OH- HPO4
2- + H2O

Limitations of Buffer Systems
1. Provide only temporary solution to acid–base
imbalance
2. Do not eliminate H+ ions
3. Supply of buffer molecules is limited

 Proteins are negatively charged
 Bind with either H+ ions or Ca2+ ions
 If pH  - binding with H+ ion 
 If pH  – binding with Ca2+ ions 
That is why in alkalosis we see tetany
varities
 Plasma proteins
 Hemoglobin
 Tissue proteins

• Proteins are quantitatively the most important buffer in
the body
• They contain both acid and basic groups
-COOH which dissociate to –COO- and H+
NH2 which accept H to form NH3
+
• pKa of protein vary but many work at pH of 7.4

Hemoglobin
• This is responsible for half of the buffering power of
the blood and has immidiate effect
• Hemoglobin is rich in histidine, which is an effective
buffer from pH 5.7 to 7.7 (pk 6.8).
• Hemoglobin exists as in red blood cells in equilibrium
as a weak acid (HHb) and a potassium salt (KHb).
• It buffers both respiratory and metabolic acids.
• Acidity in these group is influenced by oxygenation
and reduction of hemoglobin.
Hb is a weaker acid in reduced form and accepts H+ and
CO2 in tissue and reverse occur in lungs where it
become strong acid to release H+ and CO2

Mechanics…
Inside RBC
CO2 diffuses across RBC membrane (no transport
mechanism required)
CO2 + H2O H2CO3 H+ + HCO3
-
reduced form of hemoglobin weak acid (HHb) and a potassium salt (KHb).
Bicarbonate ions diffuses into plasma in exchange of
chloride ions (chloride shift)

The chloride shift or "Hamburger effect"
movement of chloride into RBCs occurs when the buffer
effects of deoxygenated haemoglobin increase the
intracellular bicarbonate concentration, and the
bicarbonate is exported from the RBC in exchange for
chloride.
Benefit-permits the plasma to be used as a storage site
for bicarbonate without changing the electrical charge of
either the plasma or the red blood cell.

2)THE RESPIRATORY SYSTEM
 Balances by changes in alveolar ventilation
Mediated by chemoreceptors within the brainstem and
the carotid and aortic bodies
 When does it comes into action ?
When chemical buffers alone fail
Respond to -changes in cerebrospinal spinal fluid pH
Eliminates -volatile acid & CO2
Time of onset- 1 to 3 min
Buffering capacity – double compared to chemical
buffer

Job- CO2 production and excretion are balanced -
maintaining PaCO2 at 40 mmHg
In fact, the lungs are responsible for eliminating the approximately
15 mEq of CO2 produced every day as a byproduct of
carbohydrate and fat metabolism.
When rate of CO2 production  (pH )
chemoreceptors at central medulla stimulated
Hyperventilation
PaCO2 normal
for every (acute) 1 mm
Hg increase in PaCO2

Minute ventilation
increases 1 to 4 L/min

Respiratory Compensation During
Metabolic Acidosis
Respiratory compensatory responses are also important
in defending against marked changes in pH during
metabolic disturbances.

Decreases in arterial blood pH
stimulate medullary
respiratory centers.
increase in alveolar ventilation lowers PaCO2
pH normal
PaCO2 normally decreases 1 to 1.5 mm Hg below 40 mm hg for every 1
meq/L decrease in plasma [HCO3
–].
Rapidly ie .1-3 mins but
steady state is achieved
in 12 to 24 h
But,
pH is never completely
restored to normal.

When does respiratory regulation fail?
Underlying Respiratory or CNS disorder

Hypoventilation

CO2 excretion reduced

Hypercapnia

pH decreased

Respiratory acidosis

Respiratory Compensation During
Metabolic Alkalosis

arterial blood pH
depress respiratory centers.
hypoventilation -----------Hypoxemia
 PaCO2
pH toward normal.
less predictable than the respiratory response to
metabolic acidosis
Because…

Later on,
Hypoxemia, due to hypoventilation
activates oxygen-sensitive chemoreceptors
stimulates ventilation and limits the compensatory
respiratory response.
Consequently, PaCO2 usually does not increase above
55 mm Hg in response to metabolic alkalosis.
As a general rule, PaCO2 can be expected to increase
0.25 to 1 mm hg for each 1 meq/L increase in [HCO3
–].

3) THE KIDNEY
 For both metabolic and respiratory acid–base
disturbances.
 Aim of kidney-
1. retain and regenerate HCO3
-
2. eliminating the non-volatile acid load(uric acid, and
incompletely oxidized organic acids)
Endogenous bases are also produced during the
metabolism of some anionic amino acids (eg, glutamate)
but the quantity is insufficient to offset the endogenous
acid production hence kidney needs to eliminate.

During ACIDOSIS what does kidney do?
three-fold response of kidney
•  reabsorption of the filtered HCO3
–
•  excretion of acids
•  production of ammonia.
activated immediately but effects are generally not
appreciable for 12 to 24 h and maximal up to 5 days.

A)Increased Reabsorption of HCO3
–

1. CO2 within renal tubular cells combines with water in
the presence of carbonic anhydrase.
2. The carbonic acid (H2CO3) formed rapidly dissociates
into H+ and HCO3
–.
3. Bicarbonate ion then enters the bloodstream while
the H+ is secreted into the renal tubule, where it
reacts with filtered HCO3
– to form H2CO3.
4. Carbonic anhydrase associated with the luminal
brush border catalyzes the dissociation of H2CO3 into
CO2 and H2O.
5. The CO2 thus formed can diffuse back into the renal
tubular cell to replace the CO2 originally consumed.

Recalimation by site
PROXIMAL TUBULES - 80% of the filtered bicarbonate
load along with sodium
DISTAL TUBULES -20% ,not sodium linked
Unlike the proximal H+ pump, the H+ pump in the distal
tubule is not linked to sodium reabsorption and is
capable of generating steep H+ gradients between
tubular fluid and tubular cells.
Urinary pH can  to as low as 4.4

Effect of urinary pH
• Weak acid drugs are more unionized in acid & more
ionized in alkaline media.
• Weak base drugs are more unionized in alkaline &
more ionized in acid media.
Alkalinization of urine (Na or K Acetate, Bicarbonate )
increase Renal excretion of weak Acid drugs e.g. Aspirin
Acidification of Urine (NH4Cl or “Vit C”) increases Renal
excretion of weak Base drugs e.g. Ephedrine &
Amphetamine.

B. Increased Excretion of Acids

After all of the HCO3
– in tubular fluid is reclaimed,
H+ secreted combine now with
HPO4
2– to form H2PO4
–

(not readily reabsorbed because of its charge)
which is eliminated in urine.
So, H+ is excreted from the body as H2PO4
–
With a pK of 6.8, it is ideal urinary buffer. Normal urine
pH-4.6 to 8.0
When urinary pH approaches 4.4, however, all of the
phosphate reaching the distal tubule is in the H2PO4
–
form; HPO4
2– ions are no longer available for eliminating
H+.

C. Increased Formation of Ammonia

After complete reabsorption of HCO3
– and consumption
of the phosphate buffer
the NH3/NH4
+ pair is The urinary buffer.
Source of NH3 - Deamination of glutamine within
proximal tubular cells
Acidemia markedly  renal NH3 production
Passively

Cell’s luminal membrane

Tubular fluid

React with H+

Form NH4
+ Combines with Cl-
Upregulated
in long term
acidosis

Renal Compensation During ALKALOSIS
Kidney does a lot of HCO3
– handling , so can also
excrete bicarbonate or reabsorb on demand.
highly effective
against metabolic alkalosis
If at all it occurs, it occurs if there is concomitant
sodium deficiency or mineralocorticoid excess.

Secreting H+ as ion itself help
neutralize pH raise by
bicarbonate secretion in the
tubule lument
In DCT
HCO3
- is
exchanged
for Cl-
Cl-

Sodium deficiency
Na+ depletion decreases ECF volume

enhances Na+ reabsorption in the proximal tubule.

[maintaining neutrality], the Na+ ion is brought across
from lumen with a Cl– ion.
when Cl– ions decrease in number in lumen(<10 mEq/L
of urine), HCO3
– must be utilized.
Increased H+ secretion in exchange for augmented Na+
reabsorption favors HCO3
– formation with metabolic
alkalosis.

Increased mineralocorticoid
Increased aldosterone

Na+ reabsorption in exchange for H+ secretion in the
distal tubules.

Increase in HCO3
– formation

Metabolic alkalosis.

Factors affecting H+ secretion/ reabsorption HCO3¯
A. CO2 concentration,
B. pH
C. Aldosterone
D. ECF volume
E. Potassium concentration
F. Chloride
 Renal system may take from hours to days to correct
the imbalance.

Base Excess & Base Deficit
defined-
the amount of acid or base(expressed in mEq/L ) that
must be added
for blood pH to return to 7.40 and PaCO2 to return to 40
mm Hg at full O2 saturation and 37°C.
−2 to +2 mEq/L
+ value = excess =metabolic alkalosis
- value = deficit =metabolic acidosis

Comparison of the base excess with the reference range
assists in determining whether an acid/base disturbance
is caused by a respiratory, metabolic, or mixed
metabolic/respiratory problem.
While carbon dioxide defines the respiratory component
of acid–base balance, base excess defines the
metabolic component.
The predominant base contributing to base excess is
bicarbonate. Thus, a deviation of serum bicarbonate
from the reference range is ordinarily mirrored by a
deviation in base excess.
Base excess is usually derived from a nomogram and
requires measurement of hemoglobin concentration.

Base excess can be estimated from the bicarbonate
concentration ([HCO3
−]) and pH by the equation
A high base excess, thus metabolic alkalosis, usually
involves an excess of bicarbonate.
It can be caused by
• Compensation for primary respiratory acidosis
• Excessive loss of HCl in gastric acid by vomiting
• Renal overproduction of bicarbonate

A base deficit, thus metabolic acidosis, usually involves
either excretion of bicarbonate or neutralization of
bicarbonate by excess organic acids.
Caused by-
• Compensation for primary respiratory alkalosis
• Diabetic ketoacidosis, Lactic acidosis,
• Chronic kidney failure, preventing excretion of acid and
resorption and production of bicarbonate
The serum anion gap is useful for determining whether a
base deficit is caused by addition of acid or loss of
bicarbonate.
Base deficit with elevated anion - addition of acid
(e.g., ketoacidosis).
Base deficit with normal anion gap - loss of
bicarbonate (e.g., diarrhea).
In the bleeding patient, there is a direct correlation between the
severity of the base deficit and the magnitude of blood loss, and
rapid correction of the base deficit is associated with more
favorable outcomes (13).
4. Monitoring the base deficit has been a popular practice in
trauma resuscitation, but the base deficit is essentially a
surrogate measure of lactic acidosis, and it has less predictive
value than serum lactate levels in trauma patients (14). Since
lactate levels are easily obtained, there is no justification for
monitoring the base deficit.

• Physiological effect of acidemia
• Respiratory acidosis
• Metabolic acidosis

PHYSIOLOGICAL EFFECTS
OF ACIDEMIA
Biochemical reactions are sensitive to changes in [H+].
[H+] is strictly regulated (36–43 nmol/L), as H+ ions have
high charge densities and “large”electric fields that affect
the strength of hydrogen bonds of molecules.
The overall effects of acidemia represent the balance
between the direct biochemical effects of H+ and the
effects of acidemia-induced sympatho- adrenal
activation.
• Direct effect on myocardial
• smooth muscle
• hyperkalemia

Severe acidosis (pH <7.20)direct myocardial and
smooth muscle depression

reduces cardiac contractility and peripheral vascular
resistance

progressive hypotension.
Severe acidosis can lead to tissue hypoxia, despite a
rightward shift in hemoglobin affinity for oxygen.
1

cardiac and vascular smooth muscle become less
responsive to catecholamines

ventricular fibrillation threshold is decreased
The movement of K+ out of cells in exchange for
increased extracellular H+ results in hyperkalemia that is
also potentially lethal.
Plasma [K+] increases approximately 0.6 mEq/L for
each 0.10 decrease in pH.
Central nervous system not much prominent with
metabolic acidosis but with respiratory.
2
3

(pH, CO2, Ventilation)
 Define - pH less than 7.35 with a PaCO2 greater
than 45 mmHg.
 How -The increase in PaCO2, in turn, decreases the
bicarbonate (HCO3
–)/PaCO2 ratio, thereby
decreasing the pH.
Cause -
 Excess CO2 in the inspired gas
 Decreased ventilation✔
 Increased production of CO2 by the body
Bicarbonate gets used
to balance

The level of PaCO2 is determined by –
rate of carbon dioxide production (VCO2) and
rate of alveolar ventilation (VA), as follows:
PaCO2 = K x VCO2 / VA where K is a constant.
What is the problem in apnea?
During apnea, PaCO2 rises by about 3 -6 mmHg per
minute.
H+ ion accumulate at a rate of 10mmol/min
This is 20 times faster than the kidney can excrete them.

Differential diagnosis.
Increased inhailation of CO2 rich gas
Alveolar hypoventilation
1. CNS –depression, Cerebral ischemia, Cerebral trauma
2. Drug-induced
3. Obesity hypoventilation (Pickwickian) syndrome
4. Neuromuscular disorders,Chest wall abnormalities
5. Respiratory -Airway obstruction , COPD
Increased CO2 production
1. Malignant hyperthermia
2. Intensive shivering
3. Prolonged seizure activity
4. Thyroid storm

Signs & symptoms
 Respiratory: Dyspnoea,
Respiratory Distress
Shallow Respiration.
 CNS: Headache,
Impaired Mental Activity
Extremely high –Drowsiness and Unresponsiveness
 CVS: Heart Depressed,
Peripheral Vasodilatation
Cerebral Vasodilation
Pulmonary Vasoconstriction .
Tachycardia.
 High CO2,depresses the conduction system of heart
particularly bundle of his ,slow ventricular rhythm can occur.

Types
1. Acute respiratory acidosis
2. Chronic respiratory acidosis

Acute respiratory acidosis
(6–12 h) completed within 5-10 min from onset of hypercapnia
the PaCO2 is elevated above 45 mm Hg with an
accompanying acidemia (pH <7.35)
compensatory response is limited.
Buffering by - hemoglobin
- exchange of extracellular H+ for Na+ & K+
from bone and the intracellular fluid compartment
CO2 + H2O ↔ H2CO3 ↔ HCO3
- + H+
H+ + Buf- ↔ Hbuf
The renal response to retain more bicarbonate is little.
As a result, pH increases by 0.008 plasma [HCO3
–]
increases only about 0.1 mEq/L for each 1 mm Hg
increase in PaCO2 above 40mmHg.

Chronic Respiratory Acidosis
PaCO2 is elevated above 45 mm Hg with a normal or
near-normal blood pH secondary to renal compensation
and an elevated serum bicarbonate (HCO3
− >30 mm
Hg).
Compensation –Renal via synthesis and retention of
HCO3
- and excretion of H+occurs after 12 to 24 h and
maximal after 3 days.
pH by 0.003 and [HCO3
–]  by 0.4meq/l for 1mmHg
in PaCO2 above 40 mm Hg

The expected change in pH with respiratory acidosis can
be estimated with the following equations:
Acute RA –
Change in pH = 0.008 × (40 – PaCO2)
Chronic RA –
Change in pH = 0.003 × (40 – PaCO2)

Treatment of Respiratory Acidosis
Oxygenation
Reverse The Imbalance
Correct Underlying Disorder
Intravenous Solutions

1)OXYGENATION –
In acute resperatory acidosis coexistent hypoxemia is
common & major threat of life is HYPOXIA not
hypercapnia or acidemia.
So O2 supplement is needed but is carefully controlled,
because the respiratory drive in these patients may
be dependent on hypoxemia, not PaCO2
“Normalization” of PaCO2 or relative hyperoxia can
precipitate severe hypoventilation.
in chronic hypercapnia, O2 therapy should be instituted
cautiously and in lowest possible since hypoxia may
be the primary and the only stimulus to respiration.
(O2 is double edged sword in RA)

2) REVERSE THE IMBALANCE between of CO2
exchange by
increasing alveolar ventilation
Because CO2 production can not be controlled except in
situations like-
1. malignant hyperthermia- dantrolene,
2. status epilepticus- muscle paralysis
3. thyroid storm- anti-thyroid medication
4. parenteral nutrition- reduced caloric intake
3) CORRECT UNDERLYING DISORDER
***Avoid rapid decrease in chronicaly elevated PCO2 to
avoid post hypercapnic metabolic alkalosis
(arrythmias, seizures  adequate intake of Cl-)

improving alveolar ventilation
Temporary measure
• Bronchodilation,
• Reversal of narcosis,
• Improving lung compliance via diuresis
When to mechanically ventilate?
1. Severe acidosis (pH <7.20),
2. CO2 narcosis (PaCO2>80mmhg),
3. Refractory severe hypoxia or apnea.
4. respiratory muscle fatigue

4) INTRAVENOUS NaHCO3 is rarely necessary, unless pH is less
than 7.10 and HCO3
– is less than 15 mEq/L ( N- 23 to 30 mEq/L)
But ,sodium bicarbonate therapy will transiently increase PaCO2:
Problems with alkali therapy- Volume expansion & CO2
production
Buffers that do not produce CO2
Carbicarb TM-mixture of 0.3 M sodium bicarbonate and 0.3 M
sodium carbonate -mainly produces sodium bicarbonate
instead of CO2
Tromethamine (THAM)-advantage of lacking sodium and
effective intracellular buffer.
are theoretically attractive alternatives; however, there is

Chronic RA- special consideration.
return PaCO2 to the patient’s “normal” baseline.

will produces the equivalent of a respiratory alkalosis
And can precipitate severe hypoventilation.

Due to decrease in [HCO3
–]
Defination pH  to less than 7.35 with HCO3
– less
than 22 mEq/L
Cause-
(1)consumption of HCO3
– by a strong nonvolatile acid
(2)renal or gastrointestinal wasting of bicarbonate
(3)rapid dilution of the extracellular fluid compartment
with a bicarbonate-free fluid.

Differential diagnosis / Types
may be facilitated by calculation of the anion gap.

Anion Gap
Use - assess acid-base status in D/D of metabolic
acidosis
HA H+ + A-
When acid is added to the body, the [H+] increases and
the [HCO3
-] decreases.
In addition, the concentration of the anion, which was
associated with the acid, increases.
This change in the anion concentration provides a
convenient way to analyze and help determine the
cause of a metabolic acidosis by calculating anion gap.

Anion gap = plasma cations − plasma anions
([Na+]+ [K+])− ([Cl−] + [HCO3
−])

([Na+]+ [K+])− ([Cl−] + [HCO3
−])
Potassium constitutes only a small proportion of total positive charge
Anion gap = ([Na+] − ([Cl−] + [HCO3
−])
Anion gap = 140 − (104 + 24) = 12 mEq/L
(Normal range = 7 − 14 mEq/L)
BUT so AG should be 0
[Na+] =135 to 145 mEq/L
[Cl−] =96 to 106 mEq/L.

If AG is high, that means some
unmeasured anions are
present
AG = Unmeasured cations −
Unmeasured anions
Why is it useful in acidosis?
A)High AG Acidosis B)Normal AG Acidosis

High AG Acidosis –
 Organic acids

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3
-
So HCO3
- used and its level decrease
in serum
Organic acids
Lactic acid
Ketoacids
Formic acid (methanol)
Oxalic acid (ethylene glycol)
Phosphate, sulphate, urate
salysilate

Disorder
Lactic acidosis(, shock liver disease)
Diabetic Ketoacidosis and starvation
Methanol poisoning
ethylene glycol poisoning
Renal failure
Salysilate -(asprin overdose)
Organic acids
Lactic acid
Ketoacids
Formic acid (methanol)
Oxalic acid (ethylene glycol)
Phosphate, sulphate, urate
Salicylate

Normal AG Acidosis –
 Bicarbonate HCO3
− by loss
As HCO3
− decrease,
charge difference is
balanced by chloride
Kidneys compensate HCO3
− loss by reabsorbing Cl-
So a normal AG acidosis is also
called hyper-chloraemic acidosis
Because Cl- 

Bicarbonate HCO3
− decreases availability of bicabonate to
neutralie H+
Cause of Normal AG Acidosis –
Diarrhea
Diarrheal fluid contains 20 to
50 mEq/L of HCO3
– because
Small bowel, biliary, and
pancreatic fluids are all rich in
HCO3
–
patients taking
carbonic
anhydrase
inhibitors
acetazolamide

Other Causes of Hyperchloremic Acidosis
• Dilutional hyperchloremic acidosis - occur when extracellular
volume is rapidly expanded with a bicarbonate-free, chloride-
rich fluid such as normal saline. HCO3
– is diluted, and this fall in
[HCO3
–] is compensated by a rise in [Cl–].
[[[[[[[[[[[This is a reason to prefer balanced salt solutions over 0.9%
saline for fluid resuscitation.]]]]]]]]
• Amino acid infusions (TPN) contain organic cations that contain
chloride in excess of organic anions and can produce
hyperchloremic metabolic acidosis
• Lastly, ammonium chloride or arginine hydrochloride (usually
given to treat a metabolic alkalosis), can cause hyperchloremic
metabolic acidosis.

Normal AG Acidosis –
 Bicarbonate HCO3
− by loss
Summary
High AG Acidosis –
 Organic acids

Unmeasured anions ----include all organic anions
(including plasma proteins), phosphates, and sulfates.
Any process that  “unmeasured anions” or 
“unmeasured cations” will increase the anion gap.
Conversely, any process that  “unmeasured anions” or
 “unmeasured cations” will decrease the anion gap.
Plasma albumin normally accounts for the largest
fraction of the anion gap (approximately 11 mEq/L).
The anion gap decreases by 2.5 mEq/L for every 1 g/dL
reduction in plasma albumin concentration.
vice- versa in cations,
Unmeasured cations ---include K+, Ca +, and Mg2+

Mild elevations of plasma anion gap up to 20 mEq/L are
not helpful diagnostically during acidosis, but values
greater than 30 mEq/L usually indicate the presence of a
high anion gap acidosis.
Metabolic alkalosis can also produce a high anion gap
because of extracellular volume depletion, an increased
charge on albumin, and a compensatory increase in
lactate production.

Urine anion gap
used to - determine whether the kidneys are capable of
appropriately acidifying urine or not
[Na+ ]+[ K+ ]−[ Cl−]
*In contrast to the serum anion gap equation, the
bicarbonate is excluded. This is because urine is acidic,
so the bicarbonate level would be negligible.
When NAGA to define the cause we use urine AG,which
is representative of the unmeasured ions in urine.
the most important unmeasured ion in urine is NH4
+
since it is the most important form of acid excretion by
the kidney.
Urine NH4+ is difficult to measure directly, but its
excretion is usually accompanied by the anion chloride.

A negative urine anion gap can be used as evidence of
increased NH4+ excretion. In a NAMA:
positive urine anion gap suggests a low urinary NH4
+
(e.g. renal tubular acidosis).
A negative urine anion gap suggests a high urinary NH4
+
(e.g. diarrhea).

diagnosed when- serum lactate is persistently 5 mmol/L or greater
and serum pH< 7.35.
Normal Lactate levels -0.3 to 1.3 mEq/L or less than two mmol/L
Lactate levels can be measured in venous or arterial blood, with equivalent results
Associated with elevated anion gap
Types based on Cause-
✔Type A(hypoxic) hypoxemia,
hypoperfusion (ischemia)
inability to utilize oxygen (cyanide poisoning)
Type B(metabolic) defect in mitochondria, ethanol, methanol,
salicylate,metformin, Malignancy(Warburg effect)
Warburg effect is the phenomenon in which cancer cells produce additional energy
through increased glycolysis followed by lactic acid fermentation
d-Lactic acidosis: Generated from glucose and carbohydrate by
bowel bacteria in short bowel syndromes

An uncommon and often undiagnosed cause of lactic acidosis is
d-lactic acidosis.
humans have a large capacity to metabolize d-lactate so nomaly
not a concern but when there ia
Jejuno-ileal bypass surgery -
absorption and accumulation of d-lactate from abnormal intestinal
bacteria cause acidosis.
All commonly used laboratory assays for lactate use l-lactate
dehydrogenase, which does not detect d-lactate.
Signs and symptoms
1. Shallow breathing, Tachypnoea
2. Muscle pain that may later lead to cramping
3. Loss of weight and loss of appetite
4. Myalgia
5. Nausea, vomiting
6. Tachycardia

Treatmnent of lactic acidosis
• Correcting the underlying conditions and stop exercise to
rehydrate.
• Restoring tissue oxygen
• IV fluids to maintain circulation
• Avoiding sodium bicarbonate –makes CO2 that
Stimulate respiratory centre Hyperventilation worsen oxygen
delivery to tissue Increase PCO2 in capillary
• Haemodialysis -Dialysis would allow bicarbonate infusion
without precipitating or worsening fluid overload.

Serious, predominantly in those with type 1 diabetes
Cause-lack of insulin  hyperglycemia progressive
ketoacidosis from the accumulation of β-hydroxybutyric and
acetoacetic acids and dehydration
Diadnosis-high anion gap
Signs and symptoms-
Tachypnea/kussmaul respirations
•Fruity odour in breath.
Treatment-
1. Fluid replacement
2. Electrolyte replacement.
3. Insulin therapy.
Ketoacidosis may also be seen following starvation or alcoholic
binges.
glucose >250 mg/dL

Types
Acute MA
most often occurs during hospitalizations, and acute critical
illnesses. It is often associated with poor prognosis, with a
mortality rate as high as 57% if the pH remains untreated at 7.20.
Chronic MA
commonly occurs in people with Chronic Kidney Disease(CKD)
detrimental changes to the bones and muscles due to Acid
buffering leads to bone fractures, renal osteodystrophy, and
muscle wasting.

Effects
Respiratory Effects
• hyperventilation (Kussmaul respirations) – fast, deep breaths
• shift of oxy-haemoglobin dissociation curve (ODC) to the right
– decreased affinity of the haemoglobin for oxygen
after 6 hours of acidosis,
decreased 2,3 DPG levels in red cells (shifting the ODC back to
the left back towards normal).
Cardiovascular Effects
• depression of myocardial contractility
• sympathetic over-activity
• resistance to the effects of catecholamines
• peripheral arteriolar vasodilatation
• venoconstriction of peripheral veins
• vasoconstriction of pulmonary arteries
• effects of hyperkalaemia on heart in chronic
Other effects
• increased bone resorption
(chronic acidosis only)
• shift of K+ out of cells
causing hyperkalaemia

Signs & symptoms
Symptoms are not specific, and diagnosis can be difficult unless
patients present with clear indications for arterial blood gas
sampling.
Extreme acidemia :
CNS: lethargy, stupor, coma, seizures
CVS: Abnormal heart rhythms (e.g., ventricular tachycardia) and decreased
response to epinephrine, both leading to low blood pressure
CNS-altered mental status such as
severe anxiety due to hypoxia,
Cranial nerve abnormalities are
reported in ethylene glycol poisoning
eg nerve VII palsies
decreased visual acuity, retinal edema
can be a sign of methanol intoxication.
GIT- vomiting, abdominal pain, and
weight gain,
CVS- Palpitations, headache MUSCLE AND BONE -muscle
weakness, bone pain, and joint pain.

COMPENSTATION
Kidney: generation of new bicarbonate
Liver: metabolism of acid anions to produce bicarbonate
but
in DKA ,ketoacids are lost in diuresis thus aren’t available for
HCO3
- regeneration

Treatment
general measures
Ventilation- if necessary a PaCO2 in the low 30s
NaHCO3-
if arterial blood pH remains below 7.20, alkali therapy, usually in
the form of a 7.5% NaHCO3 solution may be necessary.
Exogenous administration of sodium bicarbonate
time honoured method to ‘speed up’ the return of bicarbonate
levels to normal.
useful in--------- mineral acidosis (hyperchloraemic metabolic
acidosis) where there are no endogenous acid anions which can
be metabolised by the liver.
***PaCO2 may transiently rise so ventilation is important in severe
acidemia. The amount of NaHCO3
dose (1 mEq/kg) or is derived from the base excess and the
calculated bicarbonate space

*serial blood gas measurements are mandatory to avoid
complications (eg, overshoot alkalosis and sodium overload)
Q. Calculate the amount of NaHCO3 necessary to correct a base
deficit (BD) of –10 mEq/L for a 70-kg man with an estimated
HCO3
– space of 30%of ECF
A. NaHCO3 = BD × 30% × body weight in L
= –10 mEq/L × 30% × 70 L = 210 mEq
In practice, only 50% of the calculated dose (eg., 105 mEq) is
usually given, after which another blood gas is measured.
Precaution taken during NaHCO3 administration
• Avoid I.V bolus of sodacarb except in emergency.
• Correct hypokalemia before correcting acidosis
• Avoid mixing with Ca2+ to avoid precipitation.
hemodialysis with a bicarbonate dialysate-Profound or refractory
acidemia.

Bicarbonate Space
The bicarbonate space is defined as the volume to which HCO3
–
will distribute when administered intravenously.
theoretically should equal the extracellular fluid space i.e.
(approximately 25% of body weight),
in reality, it ranges anywhere between 25% and 60% of body
weight, depending on the severity and duration of the acidosis.
This variation is partly related to the amount of intracellular and
bone buffering that has taken place.

SALICYLATE POISONING-Alkalinization of the urine
ETHANOL INTOXICATION –Fomepizole
RENAL TUBULAR ACIDOSIS-
• correction of pH and electrolyte balance with alkali
therapy.
• sodium bicarbonate
• Vitamin D and oral calcium supplements

ANESTHETIC CONSIDERATIONS IN PATIENTS
WITH ACIDOSIS
• Acidosis potentiate the depressant effects of sedatives and
anesthetic agents on CNS and CVS.
How??
Because most opioids are weak bases, acidosis can increase the
fraction of the drug in the nonionized form and facilitate opioid
penetration into the brain.
• Halothane is more arrhythmogenic in the presence of acidosis.
• Succinylcholine should generally be avoided in acidotic
patients with hyperkalemia to prevent further increases in
plasma [K+].
So correct the disorder before taking into OT.

1. Defination
2. Compensation
3. Differential diagnosis
4. Types
5. Signs and symptoms
6. Treatment

(,CO2, pH, Ventilation)
Definition-a primary decrease in Paco2.
Most common acid-base abnormality observed in
patients who are critically ill.
Compensation-
in 5-10 min from onset of hypocapnia- completed
- by nonbicarbonate buffers
(hemoglobin, proteins and phosphates)
Also kidney loose HCO3 (Cl to balance charges 
hyperchloremia) and reabsorb H+.

Chronic adaptation –
2-3 days of sustained hypocapnia
- by down regulation of renal
acidification
Compensatory mechanism for respiratory alkalosis
[HCO3
-] falls 5 mEq/L for each decrease of 10 mm Hg in
the PCO2; that is, ΔHCO3 = 0.5(ΔPCO2)
The expected change in pH with respiratory alkalosis
can be estimated with the following equations:
Acute respiratory alkalosis: Change in pH = 0.008 X (40
– PCO2)
Chronic respiratory alkalosis: Change in pH = 0.017 X
(40 – PCO2)

Effects of
1. Alkalosis increases the affinity of hemoglobin for
oxygen  shifts the oxygen dissociation curve to
the left, difficult for hemoglobin to give up
oxygen to tissues.
2. Movement of H+ out of cells in exchange for the
movement of extracellular K+ into cells

hypokalemia.

3. Alkalosis increases the number of anionic binding
sites for Ca2
+ on plasma proteins

decrease ionized plasma [Ca2
+],

circulatory depression and neuromuscular irritability.
4. Respiratory alkalosis reduces cerebral blood flow.
4. In the lungs, respiratory alkalosis increases
bronchial smooth muscle tone (bronchoconstriction),
but  pulmonary vascular resistance.

Differential diagnosis
Central stimulation
Pain,Anxiety (supra-tentorial)
Ischemia ,Stroke
Tumor,Infection
Fever
Drug-induced
–Salicylates*
-Progesterone (pregnancy)
-Analeptics (doxapram)
stimulates the CNS ,alkaloids (nicotine), methylxanthines (caffeine and theophylline),
Unknown mechanism –
-Sepsis
-Metabolic encephalopathy
Iatrogenic
Ventilator-induced
Peripheral stimulation
Hypoxemia
High altitude
Pulmonary disease -CHF
-Asthma
-Pulmonary embolism
Severe anemia
Decreased carbon dioxide
production
Sedation,
Paralysis,
Hypothermia,
Hypothyroidism

Types
Chronic & Acute
The distinction between acute and chronic respiratory
alkalosis is not always made, because the
compensatory response to chronic respiratory alkalosis
is quite variable:
Plasma [HCO3
–] usually decreases 2 to 5 mEq/L for
each 10 mm Hg decrease in PaCO2
below 40 mm Hg.

Compensation in an ACUTE Respiratory Alkalosis
Mechanism: due to the lowered pCO2 there is a slight decrease in
HCO3
-.
magnitude: drop in HCO3
- by 2 mmol/l for every 10mmHg
decrease in pCO2 from 40mmHg.
limit: the lower limit of ‘compensation’ for this process is 18mmol/l
– so bicarbonate levels below that in an acute respiratory alkalosis
indicate a coexisting metabolic acidosis.
Compensation in a CHRONIC Respiratory Alkalosis
Mechanism:renal retention of acid causes fall in plasma [HCO3
- ].
magnitude: 5 mmol/l decrease in [HCO3
- ] per 10mmHg decrease
in pCO2 from 40mmHg.
limit: the limit of compensation is a [HCO3
- ] of 12 to 15 mmol/l.

Signs & symptoms
Many of the symptoms presenting are related to hypocalcemia.
CNS: Light Headedness (CBF) ,
numbness,
tingling, confusion,
blurred vision.
decreased intracranial pressure
(secondary to cerebral vasoconstriction)
CVS :Dysrhythmias ,palpitations
Dry mouth, diaphoresis
tetanic spasms of the arms and legs.
*PaCO2 of 20-25mm Hg constitute grave prognosis.

Anesthetic Considerations
Cerebral ischemia can occur from marked reduction in
cerebral blood flow during respiratory alkalosis,
particularly during hypotension.
The combination of alkalemia and hypokalemia can
precipitate severe atrial and ventricular arrhythmias.

Treatment
1. Treat the cause is the only treatment
2. O2 is given as hypoxaemia is common cause of
hyperventilation.
In absence of hypoxaemia hyperventilation need
reassurance and rebreathing in paper bag.
3. If pH>7.55 –sedate and paralyzed and put on
venilator.
4. For severe alkalemia (arterial pH >7.60), intravenous
hydrochloric acid, arginine chloride, or ammonium
chloride may be used

1. Defination
2. Compensation
4. Signs and symptoms
6. Signs & symptoms
7. Treatment
8. Anesthetic Considerations

Definition-Increase in serum HCO3
- and high pH
Compensation-
increase in paCO2
Differential diagnosis
SALINE RESPONSIVE
(chloriede -sensitive)
associated with NaCl deficiency and
extracellular fluid depletion
SALINE NON-RESPONSIVE
(chloriede -resistant)
associated with enhanced mineralocorticoid
activity

Chloride-sensitive
Gastrointestinal
Vomiting
Gastric drainage out from mouth
Chloride diarrhea
Villous adenoma obstruction
Renal
Diuretics
Posthypercapnic
Low chloride intake
Sweat
Cystic fibrosis ---------- more chloride in their sweat

Chloride-resistant
Increased mineralocorticoid activity
Primary hyperaldosteronism
Edematous disorders (secondary hyperaldosteronism)
Cushing syndrome
Bartter syndrome
Severe hypokalemia
Miscellaneous
Massive blood transfusion
Acetate-containing colloid solutions
Alkali therapy
Milk-alkali syndrome
Bone metastases
Glucose feeding after starvation

Chloride-Sensitive Metabolic Alkalosis
• Depletion of ECF renal tubules to reabsorb Na+.
• Because not enough Cl– is available to accompany all the Na+
ions reabsorbed, increased H+ secretion
• In effect, HCO3
– ions that might otherwise have been excreted
are reabsorbed, resulting in metabolic alkalosis.
**Physiologically, maintenance of ECF volume is therefore given
priority over acid–base balance.
• Because secretion of K+ ion can also maintain electroneutrality,
potassium secretion is also enhanced.
• Moreover, hypokalemia augments H+ secretion (and HCO3
–
reabsorption) and will also propagate metabolic alkalosis.
• Indeed, severe hypokalemia alone can cause alkalosis.
• Urinary chloride concentrations during a chloride-sensitive
metabolic alkalosis are characteristically low (<10 mEq/L).

EXAMPLES OF CHLORIDE SENSITIVE
• Diuretic therapy ✔✔ cause of chloride-sensitive
Diuretics, increase Na+, Cl–, and K+ excretion, NaCl
depletion, hypokalemia, and usually mild metabolic
alkalosis.
• Loss of gastric fluid ✔ Vomiting or gastric drainage
can result in marked metabolic alkalosis, extracellular
volume depletion, and hypokalemia.
• Posthypercapnic alkalosis
Rapid normalization of PaCO2 after plasma [HCO3
–] has
risen in chronic respiratory acidosis results in metabolic
alkalosis
• Infants being fed formulas containing Na+ without
chloride readily develop metabolic alkalosis because
of the increased H+ (or K+) secretion that must
accompany sodium absorption.

Chloride-Resistant
Metabolic Alkalosis
• Inappropriate increases in mineralocorticoid activity
sodium retention and expansion of ECF.

• Increased H+ and K+ secretion takes place to balance
enhanced mineralocorticoid mediated sodium
reabsorption, resulting in metabolic alkalosis and
hypokalemia.
• Urinary chloride concentrations are typically greater
• than 20 mEq/L in such cases.
[Cl- ]<10 mEq/L in chloride sensitive

Other Causes of Metabolic Alkalosis
• When patients given even large doses of NaHCO3 and renal
excretion of HCO3
– is impaired.
• The administration of large amounts of blood products and
some plasma protein–containing colloid solutions frequently
results in metabolic alkalosis because citrate, lactate, and
acetate contained in these fluids are converted by the liver into
HCO3
–.
• Patients receiving high doses of sodium penicillin (particularly
carbenicillin) can develop metabolic alkalosis.
Because penicillins act as nonabsorbable anions in the renal
tubules, increased H+ (or K+) secretion must accompany sodium
absorption.
For reasons that are not clear, hypercalcemia that results from
nonparathyroid causes (milk-alkali syndrome and bone
metastases) is also often associated with metabolic alkalosis.

Signs and symptoms
• upto HCO3− 40 mmol/l----asymptomatic.
*concerning is hypokalemia, which increases the
likelihood of cardiac arrhythmias in patients with
coronary heart disease.
• serum HCO3− >45 mmol/l---- arterial oxygen tension
(PaO2) often falls to less than 50 mm Hg (<6.6 kP)
secondary to hypoventilation, and ionized calcium
decreases (due to alkalemia).
• serum HCO3 −>50 mmol/l ----seizures, tetany,
delirium, or stupor.
These changes in mental status are probably multifactorial in
origin, resulting from alkalemia, hypokalemia, hypocalcemia, and
hypoxemia.

Treatment
• Correct underlying disorder.
• When ventilation is controlled, decreasing minute
ventilation to normalize PaCO2.
• If chloride-sensitive metabolic alkalosis -intravenous
saline and potassium (KCl).
excessive loss of gastric fluid -H2-blocker
• Acetazolamide may also be useful in edematous
patients.
• increases in mineralocorticoid activity - aldosterone
antagonists (spironolactone).
• arterial blood pH >7.60 -IV HCl (0.1 mol/L)
or
ammonium chloride (0.1 mol/L),
or
hemodialysis.

DIAGNOSIS OF
ACID–BASE
DISORDERS

ABG provides information on three physiologic processes:
• Alveolar ventilation
• Acid-base balance
• Oxygenation
1. Alveolar ventilation:
High PaCO2 (> 45 mm Hg)  alveolar hypoventilation
low PaCO2 (< 35 mm Hg) alveolar hyperventilation.
2. Acid-base balance.

3. Oxygenation:
• The PaO2 and SaO2 (amount of oxygenated haemoglobin in
the blood)
• PaO2 is used for finding out whether there is ….
• Hypoxemia which is defined as PaO2 of less than 80 mm Hg at
sea level in an adult patient breathing room air.
• PaO2 must always be interpreted in relation to concentration of
inspired oxygen FiO2 and age.
• Since the normal PaO2 in an adult breathing room air with FiO2
of 0.2 is 80 to 100 mmHg, the normal values for PaO2/ FiO2
ratio or oxygenation ratio are 400–500 mm Hg or 4.0 to 5.0
respectively.
• PaO2 /FiO2ratio of less than 200 most often indicates a shunt
greater than 20%.

What are indications for ABG analysis?
1. to assess ventilatory status, acid-base balance, and
oxygenation and the oxygen-carrying capacity of the blood
2. To assess a patient’s response to therapeutic intervention like
ventilator management, circulatory intervention or the
progression of a disease process
3. For surgical evaluation (pulmonary resections).

Concept 1
Shunt: That part of the cardiac output that returns to the left
heart without being exposed to ventilated alveoli.
Dead space: That part of inspired air that does not take part
in gas exchange.

Concept 2
How does age affect oxygenation?
PaO2 = 104–(0.27 × age)
Using this estimation, a 60-year-old patient should have
a PaO2 of 80 mm Hg.

VQ ratio
Normal V (ventilation) is 4 L of air per minute.
Normal Q (perfusion) is 5 L of blood per minute.
So, normal V/Q ratio is 4/5 or 0.8.
When the V/Q is >0.8, it means ventilation exceeds perfusion.
When the V/Q is < 0.8, there is a VQ mismatch caused by poor
ventilation or excess perfusion as in one lung anesthesia.
When V=0 (collapsed non-aerated alveoli), a shunt is
Present
When Q =0 (non-perfused alveolus), dead space is present.

Q .What is the most preferred artery for
puncture?
The radial artery on non-dominant hand is the ideal site for an
arterial puncture for the following reasons:
ƒ
1. It is small, but superficial and Stabilized.
2. It is easily compressible with better control of bleeding
3. There is no nerve nearby to worry about.
4. The collateral arch with the ulnar artery minimizes the risk of
ischemia to the hand in case of occlusion of the radial artery.
5. This must be tested using the Allen’s test

Q .How will you choose the site?
Arterial blood samples are normally obtained from adults at the
radial, brachial, femoral, or dorsalis pedis arteries.
Because radial artery(1) puncture is relatively safe and the site
easily accessible as well as convenient for checking collateral
circulation, this site is preferable.
Before doing arterial puncture one should test for collateral
circulation.
If collateral circulation is absent, the radial artery should never
be used.
The brachial artery (2)is the second choice, as it is relatively
large and easy to palpate, and has good collateral circulation;
however, it lies deeper and its proximity to the basilic vein and
median nerve makes it easy to hit them by mistake. In addition,
the lack of underlying ligaments or bone support increases the
risk of hematoma following the procedure.

The femoral artery(3) is the third choice because it is relatively
easy to palpate and it is sometimes the only site where
sampling will be possible.
However, it lies close to the femoral vein, poses increased risk
of infection, and requires prolonged monitoring after puncture.
It should be selected as a last resort and only within a hospital
setting.
Dorsalis pedis artery is also a useful site for ABG punctures
when a radial artery sample is not obtainable

Q. What are the contraindications for
arterial puncture?
1. Infections over the puncture site
2. Absence of palpable arterial pulse
3. Negative results of an Allen test/ modified Allen test (collateral
circulation test)
4. Coagulopathies OR anti coagulation therapy
5. History of arterial spasms following previous punctures
6. Severe peripheral vascular disease
7. Arterial grafts.

Q.
Is it mandatory to have arterial line for
ABG sampling?

• when more than 4 samples of arterial blood in 24
hours
are anticipated.
*change the puncture site every time, as repeated
puncture of a single site increases the likelihood of
hematoma, scarring, or laceration of the artery

Q What is Allen’s test ?
ƒ
1. Patient elevates hand and makes a fist for 20 seconds.
2. Firm pressure held against radial and ulnar arteries.
3. Patient opens the hand which should be blanched white
4. Examiner releases only ulnar compression.
5. Normal result hand color flushes—color returns within 5 to 7
seconds.
Abnormal result: Delayed or absent hand flushing indicating
inadequate collateral circulation.

Q How to collect ABG sample??
1. Allen test prior to drawing blood
2. Take sterile syringe, and coat with a layer of heparin by
taking in 1ml and then pushing it out.
3. Lying down or sitting with the arm well-supported and the
clinician should also be seated if possible. A rolled towel
positioned beneath the wrist helps hyperextend the site while
the pulse is carefully palpated.
4. Clean and prepare the site and take the sample without
allowing an air pocket to form. If the syringe needs to be
repositioned, the tip should be withdrawn to the
subcutaneous tissue to prevent damaging the artery or
tendons with the needle.
5. Press the site with sterile cause and analyze the sample
within 15 min or keep on ice if it might take a while.
6. After analysis, dispose the syringe according to guidelines.

**Dont’s**
ƒ
1.Palpate too firmly as it might inhibiting blood flow
2.Reposition a needle without first withdrawing the tip to
subcutaneous tissue
3.Ever leave bubbles in an ABG syringe or draw air in
before deairing.
4.Fail to adequately heparinize a sample to prevent
clotting (we can get pre-heparinized syringes
preferably)
5.If unavailable, take a 2 cc syringe flush it with heparin
and then use for ABG collection).

Q . What should be our timing of doing ABG?
sampling must be done during steady state i.e.
whenever there is initiation or change in oxygen therapy;
or changes in ventilatory parameters
In the patients without overt pulmonary disease a steady
state is reached between 3–10 minutes and in patients
with chronic airways obstruction it takes about 20–30
minutes after changes have been made to ventilatory
therapy

Q. Why proper handling of sample is necessary?
• Leukocytes and platelets continue to consume oxygen in the
sample after it is drawn into a syringe and carbon dioxide
continues to be produced.
• This can cause a significant fall in PaO2 and rise in PCO2 over
time at room temperature, especially in the setting of
leukocytosis or thrombocytosis.
• It is essential that the ABG sample be analyzed within 10–15
minutes at room temperature immediately be put on ice.
• An ABG sample can remain stable on ice for at least 1 hour.
• ARGUMENT -that an iced sample can remain stable for up to
several hours, but at that point it is no longer representative of
the patient’s current status and its value as a clinical tool is
severely diminished.

Q. Why is it importantant to minimize
air contact time??
If air bubbles are not removed immediately, oxygen can
diffuse into the sample and compromise the results
because they on mixing with a blood will result in gas
equilibration between the air and the blood.
Room air has a PO2 of approximately 150 mm Hg (sea
level) and a PCO2 of essentially zero.
Thus, air bubbles that mix and equilibrate with arterial
blood will shift the PaO2 toward 150 mm Hg and lower
the PCO2 of the blood sample with subsequent increase
in pH towards alkali.

HEPARIN
Although heparin is highly acidic, excessive heparin in
the sample syringe usually lowers pH only minimally,
but decreases PCO2 in direct proportion to percentage
dilution and has a variable effect on PO2.

Temperature Correction
We know, gas solubility is inversely proportionate to
temperature
So
Solubility of gas decreases as temperature increases
Both PCO2 and PO2 therefore decrease during hypothermia,
but pH increases because temperature does not appreciably
alter [HCO3
–] and the dissociation of water decreases
(decreasing H+ and increasing pH).
but Many clinicians use the measurements at 37°C regardless
of the patient’s actual temperature .
Correcting patient temperature, once commonly applied to ABG
samples, especially in patients on cardiopulmonary bypass is
no longer the standard as studies have failed to show much
clinical relevance of temperature corrected PO2 values

LACTATE
*USE --The accumulation of lactate in plasma
produces a progressive metabolic (lactic) acidosis,
which is one of the hallmarks of CN poisoning.
---Propylene glycol toxicity.
The serum lactate level is not only a diagnostic tool,
but also has predictive value;
i.e., the probability of survival is related to both the
initial lactate level (prior to treatment), and the time
required for normalization of lactate levels (called
lactate clearance).
These relationships are demonstrated in Figure.

Elevated Blood Lactate Levels In Cardiogenic Shock And Septic
Shock.
a. The graph on the left in Figure is from a study of septic patients
,and shows a direct relationship between initial lactate levels
and in-hospital mortality.
b. It also shows that mortality rates in the first 72 hours increase
dramatically when the initial lactate level exceeds 4 mmol/L.

• In one study of trauma victims with hemorrhagic
shock, there were no deaths when lactate levels
returned to normal within 24 hours, while 86% of the
patients died when lactate levels remained elevated
after 48 hours.
• Therefore, normalization of lactate levels within 24
hours can be used as an end-point of resuscitation for
hemorrhagic shock
• Studies involving patients with septic shock show that
the rate of lactate clearance has greater prognostic
value than the initial lactate level.
• As a result, serial lactate measurements are advised
for all patients with elevated lactate levels at
presentation.

PROPYLENE GLYCOL TOXICITY: Intravenous preparations of
lorazepam contain propylene glycol (830 mg/mL per lorazepam
vial of 2 mg/mL) to enhance drug solubility in plasma.
Propylene glycol is converted to lactic acid in the liver, and
excessive intake of propylene glycol can produce a toxidrome
characterized by a
• Metabolic (lactic) acidosis
• Delirium (with hallucination)
• Hypotension,
• Multiorgan failure.
An unexplained metabolic acidosis during prolonged (>24 hours)
infusions of lorazepam should prompt a measurement of the
serum lactate levels, and an elevated lactate should raise
suspicion of propylene glycol toxicity.

MEASUREMENT OF BLOOD GAS
TENSIONS & pH
Values obtained by routine blood gas measurement-
1. Oxygen tensions(PO)
2. Carbon dioxide tensions (PCO2),
3. pH,
4. [HCO3
–],-----derived using the Henderson–
Hasselbalch equation
5. base excess,-----from the Siggaard–Andersen
nomogram.
6. Hemoglobin
7. percentage oxygen saturation of hemoglobin.---from
cooximeter

Difference between arterial blood and
venous blood
oxygen tension in venous blood (normally 40 mm Hg) is due to
tissue extraction.
Venous PCO2 - 4 to 6 mm Hg higher than PaCO2,Consequently,
venous blood pH is usually 0.05 Unit lower than arterial blood

P50
This is the partial
pressure of oxygen
required to achieve 50%
haemoglobin saturation.
In the ABG machine,
this value is
extrapolated from the
measured PaO2 and
sO2.
The normal p50 value is
24-28 mmHg

Oxygen content (O2CT)
oxygen saturation (O2Sat)
values.
O2 content measures the
amount of oxygen in the blood.
Oxygen saturation measures
how much of the hemoglobin in
the red blood cells is carrying
oxygen (O2).

What is the difference between actual and
standard bicarbonate?
Actual bicarbonate—The actual bicarbonate is the value
calculated from the blood gas sample.
Standard/corrected bicarbonate is the value of the bicarbonate
had the sample been corrected to 40 mm Hg and at room
temperature. The standard bicarbonate gives an
estimate of the metabolic component causing an acid base
imbalance.
• We know that…
Base deficit/excess is the amount of alkali or acid that must be
added to a solution to restore its pH to 7.4 after it has been
equilibrated to a PCO2 of 40 mm Hg.
• So we can also say,
The base deficit/excess is the amount of deviation of the
standard bicarbonate from the normal.

1. Examine arterial pH: Is acidemia or alkalemia present?
2. Examine PaCO2: Is the change in PaCO2 consistent with a
respiratory component?
3. If the change in PaCO2 does not explain the change in arterial
pH, does the change in [HCO3
–] indicate a metabolic component?
4. Make a tentative diagnosis
5. Compare the change in [HCO3
–] with the change in PaCO2.

Does a compensatory response exist ??????????
Because arterial pH is related to the ratio of PaCO2 to [HCO3
–],
both respiratory and renal compensatory mechanisms are always
such that PaCO2 and [HCO3
–] change in the same direction. A
change in opposite directions implies a mixed acid–base disorder.
6. If the compensatory response is more or less than expected, by
definition, a mixed acid–base disorder exists.
7. Calculate the plasma anion gap in the case of metabolic
acidosis.
An elevated anion gap strongly suggests the presence of a
metabolic acidosis indicated by AG > 30 mmol/L
8. Measure urinary chloride concentration in the case of metabolic
alkalosis. Calculate the urinary anion gap to differentiate between
a GI and renal cause of a normal anion gap acidosis
If pH is NORMAL despite an abnormal CO2 and HCO3
– it must be
compensated.

Finding compensated, partially compensated, or
uncompensated ABG problems:
When PaCO2 is high, but pH is normal instead of being acidic,
and if [HCO3
-] levels are also increased, then it means that the
compensatory mechanism has retained more [HCO3
-] to maintain
the pH.
When PaCO2 and [HCO3
-] values are high but pH is acidic, then it
indicates partial compensation. It means that the compensatory
mechanism tried but failed to bring the pH to normal.
If pH is abnormal and if the value of either PaCO2 or HCO3 is
abnormal, it indicates that the system is uncompensated. This is
probably because of either respiratory or metabolic acidosis.

C a s e S t u d y 1
Consider the following:
pH = 7.50
PaCO2 = 47
HCO3
- = 32
Q1) Is it an acidosis or an alkalosis?

The pH is 7.50. This is higher than normal, so we have
an alkalosis.
pH = 7.50
PaCO2 = 47
HCO3
- = 32

Q2) Is the problem of a respiratory or metabolic nature?
pH = 7.50
PaCO2 = 47
HCO3
- = 32

The HCO3
- is 32, which is high. So we have metabolic
alkalosis.
pH = 7.50
PaCO2 = 47
HCO3
- = 32

Q3) Is there any compensation occurring? Has the body
tried to fix the problem?
pH = 7.50
PaCO2 = 47
HCO3
- = 32

We need to look at the other component, in this case,
what is the CO2?
The CO2 is outside its normal ranges. It’s 47, which is
high.
So the body is trying to fix the problem. However, the pH
is not yet back within normal ranges so a partial
compensation exists.
Conclusion:This ABG is an example of a partially
compensated metabolic alkalosis
pH = 7.50
PaCO2 = 47
HCO3
- = 32

C a s e S t u d y 2
Consider the following:
pH = 7.30
PaCO2 = 50
HCO3
-= 30
Q1) Is it an acidosis or an alkalosis?

The pH is 7.30. This is lower than normal, so we have
an acidosis.
pH = 7.30
PaCO2 = 50
HCO3
-= 30

Q2) Is the problem of a respiratory or metabolic nature?
pH = 7.30
PaCO2 = 50
HCO3
-= 30

What else is acidotic? The CO2 is 50, which is high. So
we have respiratory acidosis.
pH = 7.30
PaCO2 = 50
HCO3
-= 30

Q3) Is there any compensation occurring? Has the body
tried to fix the problem?
pH = 7.30
PaCO2 = 50
HCO3
-= 30

We need to look at the other component, being HCO3
- in this
case. Is the HCO3
- outside its normal ranges? Yes, normal
HCO3
- is between 22-28.
So the body is trying to fix this problem.
Has the body done a good job at fixing the problem? Is the
pH back within normal ranges?
No, the pH is not within normal ranges, so there is partial
compensation occurring.
Conclusion:This ABG is an example of a partially
compensated respiratory acidosis.
pH = 7.30
PaCO2 = 50
HCO3
-= 30

C a s e S t u d y 3
A 63-year-old female who was admitted with shortness
of breath. Patient appears drowsy and is on 10L of
oxygen via a mask.
an ABG reveals the following results:
PaO2: 52.5 mmHg (82.5 – 97.5 mmHg)
pH: 7.29
PaCO2: 68.2 mmHg
HCO3
–: 26 mEq/L
Base excess: +1 (-2 to +2)

PaO2: 52.5 mmHg (82.5 – 97.5
mmHg)
pH: 7.29
PaCO2: 68.2 mmHg
HCO3
–: 26 mEq/L
Base excess: +1 (-2 to +2)
Q .What does the ABG show?

Oxygenation (PaO2)-is low, patient is in respiratory failure,
however, we don’t yet know what type.
pH-reveals an acidosis and assess the CO2 to see if it is
contributing to the acidosis (↑CO2).
PaCO2 In this case, the PaCO2 is raised significantly.
In the context of low PaO2, a raised PaCO2 suggests the patient
has type 2 respiratory failure.
HCO3
–-normal, so the metabolic system isn’t compensating for the
respiratory acidosis, suggesting that this is an acute derangement.
Base excess (BE)-normal limits as there has been no significant
change in the amount of HCO3
–.
If this respiratory acidosis was chronic we would expect that the
kidneys would have generated more HCO3
–to compensate, which
would have resulted in an increased BE.
Interpretation Acute Respiratory acidosis

C a s e S t u d y 4
A 17-year-old patient presents to emergency
complaining of a tight feeling in their chest, shortness of
breath as well as some tingling in their fingers and
around their mouth. They have no significant past
medical history and are not on any regular medication.
An ABG is performed on the patient whilst they’re
breathing room air and the results are shown below:
PaO2: 105 mmHg (82.5 – 97.5 mmHg)
pH: 7.49
PaCO2: 24 mmHg (35.2 – 45 mmHg)
HCO3
–: 22 mEq/L
BE: +2 (-2 to +2)
What does ABG show??

Oxygenation (PaO2)-105 mmHg on air is at the upper limit of
normal, so the patient is not hypoxic.
pH-7.49 is higher than normal and therefore the patient is
alkalotic.
PaCO2-low, which would be in keeping with an alkalosis, so we
now know the respiratory system is contributing to the alkalosis
and is likely to be the entire cause of it.
HCO3
–- normal, ruling out a mixed respiratory and metabolic
alkalosis, leaving us with an isolated respiratory alkalosis.
Base Excess -normal, suggesting there has been no addition of
bicarbonate to cause the alkalosis, ruling out the metabolic
system as the cause.
Compensation-The bicarbonate is on the low end of normal, but
this does not represent compensation.
Compensation would involve a much more significant reduction in
HCO3
–.
Interpretation -----Respiratory alkalosis
Anxiety – panic attack Pain – causing increased respiratory rate
Hypoxia – often seen in ascent to altitude Pulmonary embolism

How does hyperventilation lead to perioral and
peripheral paresthesia?
As blood plasma becomes more alkalotic, the concentration of
freely ionized calcium, decreases
(hypocalcaemia).
Because a portion of both hydrogen ions and calcium are bound
to serum albumin, when blood becomes alkalotic, the bound
hydrogen ions dissociate from albumin, freeing up the albumin to
bind with more calcium and thereby decreasing the freely ionized
portion of total serum calcium leading to hypocalcaemia.
This hypocalcaemia related to alkalosis is responsible for the
paraesthesia often seen with hyperventilation.

C a s e S t u d y 5
a 59-year-old female who has been admitted the acute
medical ward of your hospital. The nurse tells you that
she appears short of breath despite currently receiving 3
litres of oxygen via nasal cannulae.
arterial blood gas which reveals the following results:
PaO2: 68.2 mmHg
pH: 7.30
PaCO2: 63 mmHg (35.2 – 45 mmHg)
HCO3
-: 29 mEq/L
BE: +4 (-2 to +2)

Respiratory acidosis with metabolic compensation
Does this blood gas suggest an acute or chronic
derangement in CO2?
This patient has COPD and has a chronically elevated
level of CO2.
As a result, the metabolic system has had time to
compensate via the generation and retention of HCO3
–
to oppose further decreases in pH.
This explains why the pH is only slightly acidotic, despite
a significantly raised PaCO2.
If this derangement in CO2 was acute, there would not
have been time for a compensatory response from the
metabolic system.

C a s e S t u d y 6
A 22-year-old female is brought into emergency by
ambulance with a 5-day history of vomiting and lethargy.
When you begin to talk with the patient you note that she
appears disorientated and looks clinically dehydrated.
You gain IV access, send off a routine panel of bloods
and commence some fluids. You notice an increased
respiratory rate, low blood pressure and tachycardia..
ABG are shown below (not on oxygen for ABG).
PaO2: 97.5 mmHg
pH: 7.3 (7.35 – 7.45)
PaCO2: 30.7 mmHg (35.2 – 45 mmHg)
HCO3
-: 13 mEq/L
BE: -4 (-2 to +2)

Metabolic acidosis with respiratory compensation
New investigations
Capillary blood glucose:
32 mmol/L
Urinalysis:
Glucose +++
Ketones +++
Diabetic ketoacidosis (DKA)

C a s e S t u d y 7
A 64-year-old man is admitted to emergency with central
crushing chest pain. As the nurses are getting him
attached to the ECG he is found to have a cardiac
arrest. Thankfully CPR was commenced immediately
and after 6 minutes he regained spontaneous circulation
and began breathing again.
An ABG (on 15L O2) performed following this sequence
of events reveals the following:
PaO2: 71.3 mmHg
pH: 7.14
PaCO2: 60.8 mmHg
HCO3-: 15.2 mEq/L
BE: – 9.7 (-2 to +2)

Oxygenation (PaO2) -very low, particularly in the context of 15L
O2, this suggests the presence of impaired ventilation, likely
secondary to the cardiac arrest.
pH 7.14 is low, suggesting this gentleman is acidotic. We now
need to look at the PaCO2 to assess if this is contributing (e.g.
↑CO2).
PaCO2 high, in keeping with type 2 respiratory failure and also in
keeping with a respiratory acidosis. This is again likely secondary
to impaired ventilation.
The next step is to look at the HCO3-.
HCO3- is low, suggesting that the metabolic system is also
contributing to the acidosis.
Base Excess -low, again in keeping with metabolic acidosis.
Interpretation .. Mixed respiratory and metabolic acidosis.

C a s e S t u d y 8
Baby Angela was rushed to the Emergency Room
following her mother’s complaint that the infant has been
irritable, difficult to breastfeed, and has had diarrhea for
the past 3 days.
The infant’s respiratory rate is elevated and the
fontanels are sunken.
The Emergency Room physician orders ABGs after
assessing the ABCs. The results from the ABG results
show
pH 7.39, PaCO2 27 mmHg, and HCO3
- 19 mEq/L. What
does this mean?

Metabolic Acidosis, Fully Compensated
Baby Angela has metabolic acidosis due to decreased
HCO3 and slightly acidic pH. Her pH value is within the
normal range which made the result fully compensated.

C a s e S t u d y 9
Client Z is admitted to the hospital and is to undergo
brain surgery. The client is very anxious and scared of
the upcoming surgery. He begins to hyperventilate and
becomes very dizzy. The client loses consciousness and
the STAT ABGs reveal
pH 7.61,
PaCO2 22 mmHg, and
HCO3 25 mEq/L.
What is the ABG interpretation based on the findings?

Respiratory Alkalosis Uncompensated
The results show that client Z has respiratory
alkalosis since there is an increase in the pH
value and a decrease in PaCO2 which are both
basic. It is uncompensated due to the normal
HCO3 which is within 22-26 mEq/L.

A simplified and more practical derivation of the Henderson–
Hasselbalch equation for the bicarbonate buffer is as follows:
[H+]=24× PaCO2 [HCO3
−]
This equation is very useful clinically because pH can be readily
converted to [H+] .
Note that below 7.40, [H+] increases 1.25 nEq/L for each 0.01
decrease in pH; above 7.40, [H+] decreases 0.8 nEq/L for each
0.01 increase in pH.
Example: If arterial pH = 7.28 and PaCO2 = 24 mm Hg, what
should the plasma [HCO3
–] be?

Delta Ratio
= the increase in Anion Gap / the decrease in HCO3
-
if one molecule of metabolic acid (HA) is added to the ECF and
dissociates, the one H+ released will react with one molecule of
HCO3
- to produce CO2 and H2O (buffering).
the net effect will be an increase in unmeasured anions by the one
acid anion A- (ie anion gap increases by one) and a decrease in
the bicarbonate by one.
if all the acid dissociated in the ECF and all the buffering was by
bicarbonate, then the increase in the AG should be equal to the
decrease in bicarbonate so the ratio between these two changes
(which we call the delta ratio) should be equal to one.
.

WHEN TO USE
in
HAGMA to determine if it is a ‘pure’ HAGMA
Or
if there is coexistant normal anion gap metabolic
acidosis (NAGMA) or metabolic alkalosis.
INTERPRETATION

< 0.4
hyperchloraemic normal anion gap metabolic acidosis (NAGMA)
the reason here is that the acid involved is effectively hydrochloric acid (HCl) and the
rise in plasma [chloride] is accounted for in the calculation of anion gap (ie chloride is a
‘measured anion’).
the result is that the ‘rise in anion gap’ (the numerator in the delta ratio calculation) does
not occur but the ‘decrease in bicarbonate’ (the denominator) does rise in numerical
value.
the net of both these changes then is to cause a marked drop in delta ratio (commonly to
< 0.4)
0.4 – 0.8
consider combined HAGMA + NAGMA, BUT note that the ratio is often < 1 in acidosis
associated with renal failure
1 – 2
usual for uncomplicated HAGMA.
lactic acidosis: average value 1.6
DKA more likely to have a ratio closer to 1 due to urine ketone loss (esp. if patient not
dehydrated)
> 2 a high delta ratio can occur in the situation where the patient had quite an elevated
bicarbonate value at the onset of the metabolic acidosis.
such an elevated level could be due to a pre-existing metabolic alkalosis, or to
compensation for a pre-existing respiratory acidosis (ie compensated chronic respiratory
acidosis).

METABOLIC ACIDOSIS
ASSESSMENT
a metabolic acidosis is often strongly suspected because of the clinical presentation of
the patient (eg diabetes, renal failure, severe diarrhoea).
3 clues from a typical hospital automated biochemical profile are:
(i) low ‘bicarbonate’ (or low ‘total CO2’)
(ii) high chloride
(iii) high anion gap
other useful investigations:
(i) urine tests for glucose and ketones
(ii) electrolytes (incl chloride, anion gap, ‘bicarbonate’)
(iii) plasma glucose
(iv) urea and creatinine
(v) lactate
useful additional indices in assessment of metabolic acidosis include:
(i) Anion gap
(ii) Delta ratio
(iii) Urinary anion gap
(iv) Osmolar gap
COMPENSATION

Osmolar Gap
Use: Screening test for detecting abnormal low MW solutes (e.g.
ethanol, methanol & ethylene glycol.
An elevated osmolar gap (>10) provides indirect evidence for the
presence of an abnormal solute which is present in significant
amounts.
Osmolar gap = Osmolality – Osmolarity
Osmolality (measured) Units: mOsm/kg
Osmolarity (calculated) Units: mOsm/l
Osmolarity = (1.86 x [Na+]) + [glucose] + [urea] + 9 (using values
measured in mmol/l)
Osmolarity = (1.86 x [Na+]) + glucose/18 + BUN/2.8 + 9 (using US
units of mg/dl)
NOTE: even though the units of measured (mOsm/kg) and
calculated (mOsm/l) are different, strictly they cannot be
subtracted from one another… However, the value of the

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