ACID-BASE BALANCE AND

ANION GAP
• pH of arterial blood = 7.35 – 7.45
•pH < 7.35 acidosis
•pH > 7.45 alkalosis.
• Alteration of pH value out of the range 7.35-7.45 will have
effects on normal cell function.
• pH< 6.8 or > 8.0 death occurs
 So how can the body self-regulate acid-
base balance in order to maintain pH within
the normal range?

 This is accomplished by using delicate

buffer mechanisms between the respiratory
and renal systems.
 IMPORTANT DEFINITIONS

 In terms of pH, the blood can reflect either acidemia or

alkalemia.

 The terms acidemia and alkalemia provide no specific

information about acidosis vs. alkalosis, metabolic
disorder vs. respiratory disorder, or the underlying
clinical causes.

 To characterize a patient's blood as having acidemia or

alkalemia, only one value is needed; pH.
 Acidemia indicates an acid blood pH (less than 7.35),
 Alkalemia indicates an alkaline blood pH (greater
than 7.45).
 6 7 8 9 10
4 5 11
23 12
13
pH 1
0 14

acid base

regulation mechanism maintains constant pH:

• Buffer system
• Respiratory regulation
• Renal regulation
Metabolic acidosis
– A primary physiologic process that causes a decrease
in the serum bicarbonate.
– When not complicated by other acid­base disorders,
lowers the blood pH.

Metabolic alkalosis
– A primary physiologic process that causes an
increase in the serum bicarbonate
– When not complicated by other acid­base disorders,
raises the blood pH.

Compensatory process
– Not a primary acid­base disorder, but a change that
follows a primary disorder to restore the blood pH to
normal and is not appropriately termed acidosis or
alkalosis.
 RESPIRATORY BUFFER RESPONSE

 The function of the lung in maintaining acid-base

balance is through excretion or retention of CO2.

 In alkalosis, the lung will compensate by retaining

CO2

 In acidosis, the lung excretes CO2 through expiration.

 This occurs by increasing or decreasing the rate and

depth of respiration until the appropriate amount of
CO2 has been resumed.

 This process usually takes less than 5 minutes.

 THE RENAL BUFFER SYSTEM
 The function of the kidneys in maintaining acid-base
balance is excreting or retaining bicarbonate (HCO-3).

 In acidosis, the kidneys will compensate by retaining HCO-3

 In alkalosis, the kidneys excrete HCO-3 through the urine.

 This is a very effective way for regulation of acid-base

balance but it takes hours to days to be effective.

 Both systems (respiratory and renal) work together to keep

the blood pH balanced by maintaining 1 part acid to 20
parts base (HCO3/CO2 = 20/1)
 Normal values

pH = 7.35 - 7.45

PaCO2 = 35 – 45 mm Hg

HCO3- = 22 - 26 mEq/L
 Metabolic Acids and Metabolic Acidosis

 The term "metabolic acids" includes all the

body acids EXCEPT carbon dioxide.

 The body can not get rid of metabolic acids by

expiration as carbon dioxide.

 They have to be neutralized, metabolized, or

excreted via the kidney.

 Any change in the pH unexplained by the

pCO2 indicates a metabolic abnormality.
 Metabolic acidosis
 Occurs when:
 pH of less than 7.35.
 Bicarbonate level in the blood < 22 mEq/L

-
H2CO3 CO 3-
HHCO3

H 2CO 3

== 7.4
7.4
1 : 10
20
 METABOLIC ACIDOSIS

 It is due to:
Excess of acid due to:
 increased production of organic acids
 rarely, ingestion of acidic compounds
 Inadequate Excretion of H+
Low concentration of bicarbonate.
 Excess of acid .1
a) Excess H+ Production:
– This is the commonest cause of metabolic acidosis
– It results from the excessive production of organic
acids:
Usually lactic acid as a result of anaerobic
metabolism. (This may result from local or global
tissue hypoxia).
Another form of metabolic acidosis is diabetic
ketoacidosis due to accumulation of ketone bodies.
b) Ingestion of Acids:
This is an uncommon cause of metabolic acidosis
and is usually the result of poisoning with agents
such as ethylene glycol (antifreeze) or ammonium
chloride.
Salicylate intoxication
Excessive Loss of Bicarbonate .2

The loss of small bowel contents rich in sodium

bicarbonate e.g. excessive diarrhea

Carbonic anhydrase inhibitor (e.g. Acetazolamide,

used in the treatment of acute mountain sickness
and glaucoma) may cause excessive urinary
bicarbonate losses.
- Inhibition of carbonic anhydrase slows the
conversion of carbonic acid to CO2 and water in
the renal tubule.
-Thus, more carbonic acid is lost in the urine and
bicarbonate is not reabsorbed.
 Major causes of metabolic acidosis

 Renal failure
 Diabetic ketoacidosis
 Anaerobic metabolism (any conditions
that cause tissue hypoxia)
 Starvation
 Salicylate intoxication
 Signs and symptoms of metabolic acidosis
Are mainly central nervous system, cardiovascular,
pulmonary and GI systems.
 Nervous system:
 headache, confusion, and restlessness progressing to
lethargy, then stupor or coma.
 Cardiac & pulmonary symptoms:
 dysrhythmias are common
 Kussmaul respirations occur in an effort to
compensate for the pH by blowing off more CO2.
 GIT:
 nausea and vomiting are commonly present.
 Skin:
 Warm and flushed
METABOLIC ACIDOSIS
- metabolic balance before onset of
acidosis
- pH 7.4

- metabolic acidosis
- pH 7.1
- HCO3- decreases because of excess
presence of ketones, chloride or organic
ions
- body’s compensation
- hyperactive breathing to “ blow off ”
CO2
- kidneys conserve HCO3- and eliminate H+
ions in acidic urine
- therapy required to restore metabolic
balance
- lactate solution used in therapy is
0.5 10 converted to bicarbonate ions
in the liver
 ANION GAP
 It is the difference between the sum of the major
anions and the major cations:

 AG = ( Na+ +   K+ )  -  ( Cl-   -   HCO3- )

   16 =  (140 +   4 )  -  (104  -   24 ) mMol/L

 It is sometimes calculated as 12±2

 AG indicates the unmeasured anions in the blood.

 Normal AG is due to unmeasured albumin (anion)

 ANIONS & CATIONS
(Concentration in mEq/L)

CATIONS ANIONS
Calcium: 5 Proteins: 15
Magnesium: 1.5 Organic acids: 5
Potassium: 4.5 Bicarbonate: 24
Sodium: 140 Phosphate: 2
Sulphate: 1
Chloride: 104
Total: 151 Total: 151
Under normal physiological conditions, there is
electrochemical balance, so that the sum of all
negatively charged electrolytes (anions) equals
the sum of all positively charged electrolytes
(cations).

However, several anions are not measured

routinely, leading to the anion gap.
If we measure all of them, there would be no
gap, since positives equal negatives.

However, because only Na+, K+, Cl- and HCO3-

are routinely measured, there is an anion
gap; the gap exists because more anions are
unmeasured than are cations.

Because sometimes K+ is not used in the

calculation the normal anion gap is about 12
mEq/L.
Na+ and K+ account for about 95% of total serum
cations while Cl- and HCO3- account for about
85% of the total serum anions in a healthy
individual.

An increased anion gap indicates the presence

of excessive amounts of one or more of these
anions or of some other anion.
The overall general equation can be expressed
as follows:

Na+ + K+ + UC = Cl- + HCO3- + UA

Unmeasured cations (UC): Are rarely increased
enough to decrease the anion gap.
Unmeasured anions (UA) : Lactate, phosphate,
sulfate, ketones, metabolites of some poisons,
such as ethylene glycol, plasma proteins.
Rearrangement of the equation above gives :
UA-UC= (Na++K+) - (Cl-+HCO3-)
So Anion gap (AG) = (UA-UC)
Since UC cannot change enough to affect the anion
gap and still be compatible with life, UC can be
ignored from the equation. Thus,

Anion gap = UA = (Na++K+)-(Cl-+HCO3-)

As can be seen from these equations, the AG is a

figure that indicates the amount of unmeasured
anions in serum expressed in mEq/L.
Variations in the anion gap
1- VERY LOW OR NEGATIVE ANION GAP
(rare):
Some cough medications contain
dextromethorphan bromide; bromides are
measured as chloride.
Excess unmeasured cation, as seen in lithium
toxicity;
Hypo-proteinemia (which is the most common
in this category); a 1 gm/dl decrease in serum
albumin causes a 2.5 mEq/L drop in the AG.
Presence of abnormal, positively charged
proteins (paraproteins), as may occur in multiple
myeloma.
2- ELEVATED ANION GAP:
All excess anions are buffered by bicarbonate,
and in most of the cases, elevated AG usually
means a state of metabolic acidosis whatever
the level of bicarbonate is normal or above
normal.

What level of anion gap should be

considered abnormal?
Anion gap between 16 and 20 mEq/L, no
specific anion gap acidosis can be diagnosed in
the majority of the patients.

Above 20 mEq/L the probability of a true anion

gap metabolic acidosis increases.

AG above 29 mEq/L, it is true anion gap

metabolic acidosis.

At AG of 20 mEq/L or more we should look for

the cause which may be:
Causes of anion gap metabolic acidosis:

Diabetic ketoacidosis (ketone bodies)

Renal failure ( sulphate and phosphate)
Lactic acidosis (as in hypoxia)
Alcoholic acidosis
Aspirin toxicity
Methanol ingestion
Ethylene glycol ingestion (ketone bodies)
 Non anion gap metabolic acidosis

AG =  Na+ +   K+  -   Cl-   -   HCO3-

 If the acid anion is chlorine, hyperchloremic

metabolic acidosis will result.

 Since chlorine is part of the formula for anion

gap, hyperchloremic metabolic acidosis does
not result in an increased anion gap.
 Causes of non anion gap metabolic
acidosis
 Infusion of saline

 Ingestion of acids containing Cl- (CLOROX)

 Chloride Gas intoxication

 GIT losses of bicarbonate (diarrhea, fistula)

 Renal losses of HCO3- :

 Renal tubular acidosis due to defect in proximal or distal tubules

 Hypoaldosteronism because renal mechanisms retain chloride

in an attempt to preserve ECF volume

 Early stages of renal failure

 Metabolic alkalosis
 Bicarbonate level > 26 mEq/liter
 pH > 7.45.
 It is due to:
An excess of base or
Loss of acid

H2 CO HCO -
H2CO3 3 HCO3- 3

= 7.4
11 : 40
20
 Excess base:
 Ingestion of antacids
 Excess use of bicarbonate (rapid infusion or
chronic administration)
 Use of lactate in dialysis.
 Loss of acids:
 Severe vomiting
 Gastric suction
 Movement of H+ into cells (hypokalemia)
 Hypochloremia (occur in volume depletion which
stimulate aldosterone secretion which cause H+
and K+ secretion)
 Excess administration of diuretics
 High levels of aldosterone.
 Symptoms of metabolic alkalosis

 They are mainly neurological and musculoskeletal.

 Neurologic:
 dizziness, lethargy, disorientation, seizures and coma.

 Musculoskeletal:
 Weakness, muscle twitching, muscle cramps (may be due
to hypoxia) and tetany (due to decreased ionized calcium).

 Nausea, vomiting, and respiratory depression may be present.

 It is one of the most difficult acid-base imbalances to treat.

 It is worth mention that metabolic alkalosis in hospitalized

patients is usually iatrogenic in nature.
METABOLIC ALKALOSIS
- metabolic balance before onset of alkalosis
- pH = 7.4

- metabolic alkalosis
- pH = 7.7
- HCO3- increases because of loss of chloride
ions or excess ingestion of NaHCO3

- body’s compensation
- breathing suppressed to hold CO2
- kidneys conserve H+ ions and eliminate
HCO3- in alkaline urine

- therapy required to restore metabolic

balance

1.25 25 - HCO3- ions replaced by Cl- ions

 Components of the Arterial Blood Gas
 pH: measurement of acidity or alkalinity, based on the
hydrogen (H+) ions present, normal range is 7.35 to
7.45

 PaO2: the partial pressure of oxygen that is dissolved

in arterial blood, normal range is 80 to 100 mm Hg

 SaO2: the arterial oxygen saturation, normal range is

95% to 100%

 PaCO2: the amount of carbon dioxide dissolved in

arterial blood, normal range is 35 to 45 mm Hg
 HCO3: It is the calculated value of the amount of
bicarbonate in the bloodstream, normal range is 22 to
26 mEq/liter
 The base excess (B.E)
– It is the number of mEq of strong acid which has to
be added to a litre of fully saturated blood at 37°C
to bring its pH to 7.4 when the PCO2 = 40mmHg.

– Thus, it indicates the level of bicarbonate in the

system.

– When HCO3 is ↓ → B.E ↓

– It is the commonest parameter used to express

non-respiratory pH disturbances.

– The normal range is –2 to +2 mEq/liter.

0 = normal
+ve figures = metabolic alkalosis (↑ HCO3)
-ve figures = metabolic acidosis. (↓ HCO3)