225

WATER AND ACID BASE BALANCE

WATER
1 Give an account of water distribution and its balance in the body.
2 Water toxicity.
3 Describe the rennin-angitensin - aldosterone system and its
importance. Pon. May 201
Water distribution
1 Body maintains a nearly constant amount of water that is approximately 50% to
60% of body weight in adults and 75% of body weight in children.
2 60% of the total body water is intracellular and 40% extracellular.
3 The extracellular water includes the fluid in plasma (blood after the cells have
been removed) and interstitial water (the fluid in the tissue spaces, lying between
cells).
4 Transcellular includes gastrointestinal secretions, urine, sweat, and fluid that has
leaked through capillary walls because increased hydrostatic pressure or
inflammation.
Water Balance:
Intake: 2500 ml/day
1. Exogenous water: Ingested water and beverages, water content of solid foods
constitute the exogenous source of water.
2. Endogenous water: The metabolic water produced within the body is the
endogenous water. This water (300-350 ml/day) is derived from the oxidation of
foodstuffs. On an average/ about 125 ml of water is generated for 1,000 Cal
consumed by the body.
Output: 2500 ml/day
1 Urine : In a healthy individual, the urine output is about l-2 l/day
2 Lung: During respiration about 400 ml/day is lost through the expired air.
3 Skin: About 450 ml/dayis lost through skin as sweat. The loss of water by
perspiration (via skin) and respiration (via lungs) is collectively referred to as
insensible water loss.
4 Fecal: A bout 150 ml/day is lost through feces in a healthy individual

Water toxicity: Overhydration

226
1
2

Overhydration or water intoxication is caused by excessive retention of water in the

body.
This may occur due to excessive intake of large volumes of salt free fluids, renal
failure, overproduction of ADH etc. Overhydration is observed after major trauma or
operation, lung infections etc.
Water intoxication is associated with dilution of ECF and ICF with a decrease in
osmolality. The clinical symptoms include headache, lethargy and convulsions. The
treatment advocated is stoppage of water intake and administration of hypertonic
saline.
ACID BASE BALANCE

Questions:
1. What is the normal pH? How is regulated? Write in detail about the Renal
Mechanism of regulation of pH. Pon May 2009
2. What is the normal pH of the blood? Explain how kidney regulates acid base
balance. Write a note on metabolic acidosis. Pon Nov 2010
3. What is the normal pH of blood? Explain the different mechanisms involved in
the maintenance of acid base balance. Pon Nov 2011
4. Describe the different mechanisms by which human body regulates pH of blood.
Pon May 2013
5. What is normal pH of blood? Explain the various a mechanism by which normal
pH of blood is maintained. Feb 2005
6. What is normal blood pH? Write a note on blood buffers. What is the acid base
status respiratory acidosis and how it is compensated by the buffers. April 1999.
7. Write in detail diagrammatically the reaction mechanisms by which HCO3 is
reclaimed and regenerated in kidneys. What is meant by metabolic acidosis and
how it is compensated: March 2002
8. Write how acid base balance is maintained in the body. Mention causes and
biochemical alterations of metabolic acidosis. Oct 2003
9. Discuss the regulation of blood pH. April 1994
10.Write in detail diagrammatically the reaction mechanisms by which HCO3 is
reclaimed and regenerated in kidneys. What is meant by metabolic acidosis and
how it is compensated? March 2002
11.Write how acid base balance is maintained in the body. Mention causes and
biochemical alterations of metabolic acidosis. Oct 2003
12.What is normal blood pH? Write a note on blood buffers. What is the acid base
status in respiratory acidosis and how it is compensated by the buffers? April
1999
Short notes:
1. Lactic acidosis - Nov 1993
2. Metabolic acidosis- Nov 1994; April 1995; Feb 2006; Aug 2007; April 2001; April
1998; April 2000
3. Respiratory acidosis- Nov 1995
4. Anion gap and its diagnostic importance. August 2005
5. Role of kidneys in acid base balance April 2001

227
6.
7.
8.
9.

Write the difference between metabolic and respiratory acidosis. April 2000
S.N: Write briefly on maintenance of pH of blood. Oct 99
S.N: Definition, expression and significance of Km value. Oct 2003
Discuss the role of kidney in acid base balance. Pon Nov 2007

Introduction:
1. Normal pH of blood is 7.4 (7.35 to 7.45); the pH of interstitial fluid is 0.5 units
below that of plasma.
1. <7.3 is acidosis; <7 is incompatible with life.
2. >7.5 is alkalosis and >7.8 is incompatible with life.
2. Functions of hydrogen ions:
1. Difference in H+ concentration acts as a driving force for oxidative
phosphorylation in mitochondria
2. Provides Surface charge and structure of proteins
3. Helps ionization of week acids and facilitates their physiological functions.
3. Normal Acid and base production during metabolic activities:
Acid

Source

H2Co3

Cellular oxidation.

Sulphuric acid

Oxidation of sulphur of ingested proteins

Phosphoric acid

Oxidation of phosphorus of ingested

proteins, nucleoproteins and
phospholipids.

Lactate and keto

acids

Normal metabolic activities

Basic
substances

food which is alkaline in nature

4. Definitions:
1. Acids: proton donors; an acid is defined as any compound, which forms
hydrogen ions in solution.
2. Base: Proton acceptors; A base is a compound that combines with hydrogen
ions in solution.
3. Week acid and base: ionize incompletely in solutions
4. Strong acid and base: ionize completely in solutions
5. Dissociation constant (Ka): the ratio between dissociated (H+ and A-) and
un dissociated substance (HA) is a constant at equilibrium. The pH at which
the acid is half ionized is called pKa.
a. Ka = [H+] [A-]
i. [HA]
6. pH is the negative of the logarithm of hydrogen ion concentration: 7 is
neutral pH.
1. pH =
1

228
7.
log [H+]
8. Henderson Hasselbalch equation:
pH = pKa + log [base]
[acid]
REGULATION OF BLOOD PH
Normal pH
1. The normal pH of the blood is maintained in the narrow range of 7,35-7.45, i.e.
slightly alkaline.
2. <7.3 is acidosis; <7 is incompatible with life. >7.5 is alkalosis and >7.8 is
incompatible with life.
Buffers:
The body has developed three lines of defense to regulate the body's acid-base
balance and maintain the blood pH (around 7.4).
(1) Blood buffers
(2) Respiratory mechanism
(3) Renal mechanism.
BLOOD BUFFERS:
1) A buffer may be defined as a solution of a weak acid (HA) and its salt (BA) with a
strong base. The buffer resists the change in pH by the addition of acid or alkali and
the buffering capacity is dependent on the absolute concentration of salt and acid.
2) The blood contains 3 buffer systems.
(1) Bicarbonate buffer
(2) Phosphate buffer
(3) Protein buffer
Bicarbonate buffer system:
(1) Sodium bicarbonate and carbonica cid (NaHCO3- H2CO3) is the most predominant
huffer system of the extracellular fluid, particularly the plasma. Carbonic acid
dissociates into hydrogen and bicarbonate ions.
H2Co3 H+ + HCo3(2) Henderson-Hasselbalch equation for bicarbonate buffer is:

(3) As per this equation, pH is dependent on ratio of the concentration of the base,
HCO3 to acid H2CO3.
(a) The plasma bicarbonate (HCO3) conceritration is around24 mmol. Carbonic
acid is a solution of CO2 in water.
(b) lts concentratioins given by the product of pco2 (arterial partial pressure of
CO2 = 49 mm Hg) and the solubility constant of CO2 (0.03). Thus H2CO3 = 40
x 0.03 = 1.2 mmol/L.
(c) Substituting the values (blood p H = 7.4; pK a for H2CO3 = 6.1; HCO3 = 24
mmol/l; H2CO3 = 1.2 mmol/L, in the above equation

229
7.4 = 6.1 + log 24
1.2
= 6.1 + log 20
= 6.1 + 1.3
= 7.4
(4) lt is evident that at a blood pH 7.4, the ratio of bicarbonate to carbonic acid is 20 :
1. Thus, the bicarbonate concentration is much higher (20 times) than carbonic
acid in the blood. This is referred to as alkali reserve and is responsible for the
effective buffering of H+ ions, generated in the body.
Phosphate buffer system:
1. Sodium dihydrogen phosphate and disodium hydrogen phosphate ( NaH2POaNa2HPOa)
constitute the phosphate buffer. lt is mostly an intracellular
buffer and is of less importance in plasma due to its low concentration.
2. With a pK of 6.8, the phosphate buffer would have been more effective, had it
been present in high concentration. lt is estimated that the ratio of base to acid for
phosphate buffer is 4 compared to 20 for bicarbonate buffer.
Protein buffer system:
1) The plasma proteins and hemoglobin together constitute the protein buffer system
of the blood. The buffering capacity of proteins is dependent on the pK of ionizable
groups of amino acids. The imidazole group of histidine (pK = 6.7) is the most
effective contributor of protein buffers. The plasma proteins account for about 2%
of the total buffering capacity of the plasma.
2) Hemoglobin of RBC is also an important buffer. lt mainly buffers the fixed acids,
besides being involved in the transport of gases (O2 and CO2).
RESPIRATORY MECHANISM FOR PH REGULATION:
1) Respiratory system provides a rapid mechanism for the maintenance of acid-base
balance. This is achieved by regulating the concentration of carbonic acid (H2CO3)
in the blood i.e. the denominator in the bicarbonate buffer system.
2) The large volumes of CO2 produced by the cellular metabolic activity endanger
the acid base equilibrium of the body. But in normal circumstances, all of this CO2
is eliminated from the body in the expired air via the lungs, as summarized below.
Carbonica nhydrase
H2CO3 --------------------- CO2+ H2O.
3) The rate of respiration (or the rate of removal of CO2) is controlled by a respiratory
centre, located in the medulla of the brain. This centre is highly sensitive to
changes in the pH of blood. Any decrease in blood pH causes hyperventilation to
blow off CO2, thereby reducing the H2CO3 concentration. Simultaneously the H+
ions are eliminated as H20. Respiratory control of blood pH is rapid but only a
short term regulatory process, since hyperventilation cannot proceed for long.
4) Hemoglobin as a buffer :
a. Hemoglobin is also important in the respiratory regulation of pH. At the
tissue level, hemoglobin binds to H+ ions and helps to transport CO2 as
HCO2 with a minimum change in pH (referred to as isohydric transport).
b. ln the lungs, as hemoglobin combines with 02, H+ ions are removed
which combine with HCO3 to form H2CO3.The latter dissociates to

230
release CO2 to be exhaled. The plasma CO2 diffuses into the RBC along
the concentration gradient where it combines with water to form H2CO3.
This reaction is catalysed by carbonic anhydrase (alsocalled carbonate
dehydratase).
c. In the RBC, H2CO3 dissociates to produce H+ and HCO3 . The H+ ions
are trapped and buffered by hemoglobin. As the concentration of HCO3
increases in the RBC, it diffuses into plasma along with the concentration
gradient, in exchange for Cl- ions, to maintain electrical neutrality. This
phenomenon, referred to as chloride shift, helps to generate HCO3.
RENAL MECHANISM FOR PH REGULATION:
1. The renal mechanism tries to provide a permanent solution to the acid-base
disturbances. This is in contrast to a short term respiratory mechanism.
2. The kidneys regulate the blood pH by maintaining the alkali reserve, besides
excreting or reabsorbing the acidic or basic substances.
3. The pH of urine is acidic (-6.0). The H+ ions generated in the body are eliminated
by acidified urine.
Carbonic anhydrase and renal regulation of pH:
1. The enzyme carbonic anhydrase is of central importance in the renal regulation of
pH which occurs by the following mechanisms.
i. Excret ion of H+ ions
ii. Reabsorption of bicarbonate
iii. Excretion of titratable acid
iv. Excretion of ammonium ions.
2. Excretion of H+ ions: Carbonic anhydrase catalyses the production of carbonic
acid (H2CO3) from CO2 and H2O in the renal tubular cell. H2CO3 then dissociates
to H+ and HCO3. The H+ ions are secreted into the tubular lumen in exchange for
Na+. The Na+ in association with HCO3 is reabsorbed into the blood. This is an
effective mechanism to eliminate acids (H+) from the body with a simultaneous
generation of HCO3.
3. Reabsorption of bicarbonate: Bicarbonate freely diffuses from the plasma into
the tubular lumen. Here HCO3 combines with H+, secreted by tubular cells, to
form H2CO3. H2CO3 is then cleaved by carbonic anhydrase (of tubular cell
membrane) to form CO2 and H2O. CO2 diffuses into the tubular cells along the
concentration gradient. In the tubular cell, CO2 again combines with H2O to form
H2CO3 which then dissociates into H+ and HCO3. The H+ is secreted into the
lumen in exchangef or Na+. The HCO3 is reabsorbed into plasma in association
with Na+.

231
4.
x
r
e
i
o
n

E
c
t

of titratable acid:
Titratable acidity refers to the number of milliliters of N/ l0 NaOH required to
titrate 1 liter of urine to pH 7.4. Titratable acidity reflects the H+ ions
excreted into urine which resulted in a fall of pH from 7.4 (that of blood).
The excreted H+ ions are actually buffered in the urine by phosphate buffer.
5. Excretion of ammonium ions:
This is another mechanism to buffer H+ ions secreted into the tubular fluid.
The H+ ion combines with NH3 to form ammonium ion (NH4+). The renal
tubular cells deaminate glutamine to glutamate and NH3. This reaction is
catalysed by the enzyme glutaminase. The NH3, liberated in this reaction,
diffuses into the tubular lumen where it combines with H+ to form NH4.
Ammonium ions cannot diffuse back into tubular cells and, therefore, are
excreted into urine. Renal regulation via NH4, excretion is very effective to
eliminate large quantities of acids produced in the body.
6. Carbon dioxide-the central molecule of ph regulation:
CO2 is of central importance in the acid-base balance of the body. lt has the
ability to combine with H2O to from H2CO3 which can dissociate to HCO3
and H+.
Buffers of intracellular fluids:
The H+ ions generated in the cells are exchanged for Na+ and K+ ions. This is
particularly observed in skeletal muscle which reduces the potential danger of H+
accumulation in the cells.
ACID BASE DISTURBANCES (Acidosis and alkalosis)
1. Body maintains pH in a very range around 7.4 and life is impossible beyond the range
of 7 to 7.6.
2. Classification of acid base disturbances:
a. Acidosis-a decline in blood pH
i. Metabolic acidosis-due to a decrease in bicarbonate.
ii. Respiratory acidosis-due to an increase in carbonic acid.
b. Alkalosis-a rise in blood pH
i. Metabolic alkalosis-due to an increase in bicarbonate.

232
ii. Respiratory alkalosis-due to a decrease in carbonic acid.
c. Mixed type of disorders
d. Compensated states: in real clinical conditions a person will be in different
states of
compensation by altering pCo2 and bicarbonate levels through
various mechanisms.
i. uncompensated
ii. partially compensated
iii. Fully compensated
3. The terms acidemia and alkalemia, respectively, refer to an increase or a decrease in
H+ ion concentration in blood. They are not commonly used.
4. ANION GAP
a. The total concentration of cations and anions (expressed as mEq/l) is equal in
the body fluids. This is required to maintain electrical neutrality.
b. The commonly measured electrolytes in the plasma are Na+, K+, Cl- and
HCO3. Na+ and K+ together constitute about 95% of the plasma cations. Cland HCO3 are the major anions, contributing to about 80% of the plasma
anions.
c. The remaining 20% of plasma anions (not normally measured in the laboratory)
include proteins, phosphate, sulfate, urate and organic acids.
d. Anion gap is defined as the difference between the total concentration of
measured cations (Na+ and K+) and that of measured anion (Cl- and HCOj).
e. The anion gap (A-) represents the unmeasured anions in the plasma which may
be calculated by substituting the normal concentration of electrolytes (mEq/l).
Na++ K+ = Cl- + HCO- + A- (anion gap)
136+4 = 100+25 + A- (15 mEq/l)
f. The anion gap in a healthy individual is around 15 meq/l (range 8-18 meo/l).
Acid-base disorders are often associated with alterations in the anion gap.
g. Metabolic acidosis may exist with high or normal anion gap depending on
clinical state. Classification by Anion Gap
a. 'High anion gap metabolic acidosis'
b. 'Normal anion gap metabolic acidosis'
METABOLIC ACIDOSIS:
1. Definition: It refers to primary deficit of bicarbonate due to accumulation of acid
metabolites or depletion of bicarbonate due to buffering.
2. Causes:
1. Diabetes
a.
b.
c.

mellitus (ketoacidosis)
Renal failure
Lactic acidosis
Severe diarrhea

233
d. Renal tubular acidosis
2. Metabolic acidosis is due to an excessive production of organic acids
which combine with NaHCO3 and deplete the alkali reserve.
NaHCO3 + Organic acids --- Na salts of organic acids + CO2
3. Metabolic acidosis is commonly seen in severe uncontrolled diabetes
mellitus which is associated with excessive production of acetoacetic
acid and b-hydroxybutyric acid (both are organic acids).
Anion gap and metabolic acidosis :
a. Increased production and accumulation of organic acids causes an elevation
in the anion gap. This type of picture is seen in metabolic acidosis
associated with diabetes (ketoacidosis).
b. High Anion Gap Metabolic Acidosis:
i. Renal failure: The excretion of H+ as well as generation of
bicarbonate are both deficient.
ii. Diabetic ketoacidosis
iii. Alcoholic ketoacidosis
iv. Starvation ketoacidosis
v. Lactic acidosis: Normal lactic acid content in plasma is less than 2
mmol/L. It is increased in tissue hypoxia, circulatory failure, and
intake of biguanides. Lactic acidosis causes a raised anion gap.
c. Normal Anion Gap Metabolic Acidosis:
vi. When there is a loss of both anions and cations, the anion gap is
normal, but acidosis may prevail.
vii. Diarrhea: Loss of intestinal secretions lead to acidosis.
Bicarbonate, sodium and potassiumare lost.
viii. Renal tubular acidosis may be due to failure to excrete acid or
reabsorb bicarbonate.
d. Decreased Anion Gap is Seen in
ix. Hypoalbuminemia
x. Multiple myeloma (paraproteinemia)
xi. Bromide intoxication
xii. Hypercalcemia

4.

5.

Major Effects of a Metabolic Acidosis

1. Respiratory Effects
1. Hyperventilation ( Kussmaul respirations) - this is the

compensatory response
2. Shift of oxyhaemoglobin dissociation curve (ODC) to the right
3. Decreased 2,3 DPG levels in red cells (shifting the ODC back to

the left)
2. Cardiovascular Effects

234
1.
2.
3.
4.

Depression of myocardial contractility

Sympathetic over activity
Peripheral arteriolar vasodilatation
Effects of hyperkalaemia on heart

3. Other Effects
a. Increased bone resorption (chronic acidosis only)
b. Shift of K+ out of cells causing hyperkalaemia
6. Compensation:
1. Respiratory:
i) Compensation for a metabolic acidosis is hyperventilation to decrease
the arterial pCO2.called Kussmauls respiration.
ii) Maximal compensation takes in 12 to 24 hours
2. Renal:
i) In metabolic acidosis renal compensation occurs slowly by excreting
NH4+ ions and generation of new bicarbonate; This usually occurs as a
consequence of an increase in ammonium excretion.
7. Laboratory values:
Stage
Metabolic acidosis Low
Uncompensated
Low
Partially compensated

pH
Low
Low
Low

HCO3 PaCO2
N
<20
N
<20
Low Low <20

Fully compensated N

Low

Low

Ratio

20

5. Treatment: This is done by giving bicarbonate which is calculated on

the basis of deficit:

Sodium bicarbonate in mEq= body wt in Kg X 0.2 base excess in mEq/L
METABOLIC ALKALOSIS:
1. When acid is lost or base is gained bicarbonate level increases and this is
called metabolic alkalosis.
2. Causes of loss of acid:
a. Loss of HCL from stomach leading to hypochloremic alkalosis in :
a. Severe vomiting when gastric HCL is lost;
b. Gastric aspiration for therapeutic reasons
b. hyperaldosteronism

235
a. There is retention of sodium and loss of potassium leadind
to hypokalemia.
b. The increased aldosterone levels lead to increased distal
tubular Na+ reabsorption and increased K+ & H+ losses.
c. The increased H+ loss is matched by increased amounts of
renal reabsorption of HCO3- .
d. The net result is metabolic alkalosis with hypochloraemia
and hypokalaemia.
e. Due to excess in H+ in urine the pH of urine remains
acidic(Paradoxic acidosis)
c. Intake of alkali (milk alkali syndrome)
d. Diuretic therapy
3. Types of Metabolic alkalosis:
1. Chloride responsive: urinary chloride level is less than 10 mmol/l (as
seen in vomiting , gastric aspiration and diuretic therapy) and responds
to NaCl infusion.
2. Choride resistant: urinary chloride level is more than 10 mmol / l (as
seen in hyperaldosteronism and hypertension) and does not respond to
NaCl infusion.
4. Complications:
1.

decreased myocardial contractility

2.

arrhythmias

3.

decreased cerebral blood flow

4.

confusion

5.

mental obtundation
6. neuromuscular excitability
5. Compensatory mechanisms:
1. Alkalosis depresses respiratory centre and the will be hypoventilation and
retention of CO2 which will increase carbonic acid.
2. Kidneys conserve more H+ and excretes more HCO33. Complete correction of acidosis will be effective only if hypokalemia is
corrected and the cause is treated.
6. Management:
1. Correct cause
2. Correct the deficiency which is impairing renal bicarbonate excretion (ie
give chloride, water and K+)
3. Expand ECF Volume with N/saline
4. Supportive measures: e.g. give O2 in view of hypoventilation;

236
5. Avoid hyperventilation as this worsens the alkalaemia
RESPIRATORY ACIDOSIS:
1. Respiratory acidosis refers to primary increase in carbonic acid; arterial pCO2 is
raised
2. At onset, the acidosis is designated as an 'acute respiratory acidosis'. The
body's initial compensatory response is limited during this phase.
3. As the body's renal compensatory response increases over the next few days,
the pH returns towards the normal value and the condition is now a 'chronic
respiratory acidosis'.
4. The differentiation between acute and chronic is determined by time but occurs
because of the renal compensatory response
Causes of Respiratory Acidosis
1. Inadequate Alveolar Ventilation
1. Central Respiratory Depression
a. CNS trauma,
b. infarct,
c. haemorrhage
d. tumour
2. Drug depression of resp. centre
a. opiates,
b. sedatives,
c. anaesthetics
3. Poliomyelitis
4. Tetanus
5. Cardiac arrest with cerebral hypoxia
2. Nerve or Muscle Disorders
1. Guillain-Barre syndrome
2. Myasthenia gravis
3. Muscle relaxant drugs
4. Toxins e.g. organophosphates, snake venom
5. Various myopathies
3. Lung
1. Pulmonary oedema
2. Adult respiratory distress syndrome
4. Airway Disorders
1. Upper Airway obstruction
2. Bronchospasm/Asthma
5. Over-production of Carbon Dioxide
1. Malignant Hyperthermia
6. Increased Intake of Carbon Dioxide
Compensation:
1. The compensatory response is a rise in the bicarbonate level (acute)

237
1. immediate component which raises the bicarbonate slightly.
2. delayed component where a further rise in plasma bicarbonate due to
enhanced renal retention of bicarbonate. (chronic)
Buffering in Acute Respiratory Acidosis:
1. The compensatory response to an acute respiratory acidosis is limited to

buffering.
2. Ninety-nine percent of the buffering of an acute respiratory acidosis
occurs intracellularly.
3. Proteins (especially haemoglobin in red cells) and phosphates are the
most important buffers
4. These take up the H+ produced from the dissociation of H2CO3.
Buffering in Chronic Respiratory Acidosis:
1. With continuation of the acidosis, the kidneys respond by retaining

bicarbonate.
2.

The renal response in underway by 6 to 12 hours with a maximal effect

reached by 3 to 4 days.

3. The response occurs because increased of intracellular pCO 2 in proximal

tubular cells and this causes increased H + secretion from the PCT cells into the
tubular lumen.
4.

This results in:

1.
2.
3.
4.

increased HCO3 production

increased Na+ reabsorption
increased 'NH3' production to 'buffer' the H+ in the tubular lumen
so urinary excretion of NH4Cl increases

1. In summary, the compensation for hypercapnia is:

Acute: Buffering only and predominantly intracellular (99%)
Chronic: Renal retention of bicarbonate (in addition to buffering)
The pCO2 rapidly returns to normal with restoration of adequate
alveolar ventilation
Treatment:
1. Ventilation and O2 therapy
2. Treat aetiology.

238

RESPIRATORY ALKALOSIS:
Definition:
A respiratory alkalosis is a primary acid-base disorder in which arterial pCO 2
falls to a level lower than expected.
A respiratory alkalosis is due to increased alveolar ventilation
Causes of Respiratory Alkalosis
1. Central Causes
Head Injury
Stroke
Anxiety-hyperventilation syndrome
Increased intra cranial pressure (e.g. Brain tumour; head injury)
Brain stem injury
Septicaemia; meningitis
2. Drugs: salicylate intoxication
3. Iatrogenic
Excessive controlled ventilation
Compensation:
Compensation in an ACUTE Respiratory Alkalosis
1. The buffering is predominantly by protein and occurs intracellularly;
2. There is a drop in HCO3Compensation in a CHRONIC Respiratory Alkalosis
1. Renal loss of bicarbonate causes a further fall in plasma bicarbonate
Complications:
Acute hypocapnia causes a reduction of serum levels of potassium and phosphate
secondary to increased intracellular shifts of these ions. A reduction in free serum
calcium also occurs. Calcium reduction is secondary to increased binding of
calcium to serum albumin. Many of the symptoms present in persons with
respiratory alkalosis are related to the hypocalcaemia.
Management:
1. Respiratory alkalosis itself is rarely life threatening. Therefore, emergent
treatment is usually not indicated unless the pH level is greater than 7.5.
Because respiratory alkalosis usually occurs in response to some stimulus,
treatment is usually unsuccessful unless the stimulus is controlled.
2. In hyperventilation syndrome, patients benefit from reassurance, re breathing
into a paper bag during acute episodes, and treatment for underlying
psychological stress.
NORMAL SERUM ELECTROLYTES:
pH:
7.4
Bicarbonate:
22 to 26 mmol/l
Chloride:
96 to 106 mmol/l
K:
3.5 to 5 mmo/l

239
Sodium:
136 to 145 mmol/l
pCo2:
35 to 45 mm Hg
pO2:
80 to 100 mm of Hg
Measurement of acid base parameters
1. Blood gas analyser : for pco2 and o2 from arterial blood samples
2. Venous blood by titration method ; bicarbonate is estimated at pH 7.4 and from
other electrolytes value anion gap is calculated.
LACTIC ACIDOSIS :
1. Lactic acidosis is a common cause of metabolic acidosis.
2. Each day the body has an excess production of about 1500 m.mols of lactate
which enters the blood stream and is subsequently metabolised mostly in the
liver.
3. Lactate is produced from pyruvate in a reaction catalysed by lactate
dehydrogenase:
Pyruvate + NADH + H+ <=> Lactate + NAD+
4. Lactate is metabolised predominantly in the liver (60%) and kidney (30%) 6.
5. Half is converted to glucose (gluconeogenesis) and half is further metabolised
to CO2 and water in the citric acid cycle.
6. The result is no net production of H + (or of the lactate anion) for excretion from
the body.
7. Other tissues can use lactate as a substrate and oxidise it to CO 2 and water but
it is only the liver and kidney that have the enzymes that can convert lactate to
glucose.
8. Mechanisms involved in Lactic Acidosis : Lactic acidosis can occur due to:
1. excessive tissue lactate production
2. impaired hepatic metabolism of lactate
9. Causes of Lactic Acidosis
Classification of Some Causes of Lactic Acidosis (Cohen & Woods,
1976)
Type A Lactic Acidosis : Clinical Evidence of Inadequate Tissue
Oxygen Delivery

Anaerobic muscular activity

generalised convulsions
Tissue hypoperfusion
o septic shock
o
cardiogenic or hypovolaemic shockhypotension;
o cardiac arrest;
o acute heart failure;
Reduced tissue oxygen delivery or utilisation
o hypoxaemia,
o carbon monoxide poisoning,

Type B Lactic Acidosis: No Clinical Evidence of Inadequate Tissue

Oxygen Delivery

240

type B1 : Associated with underlying diseases

o ketoacidosis,
o leukaemia,
o
lymphoma,
o AIDS
type B2: Assoc with drugs & toxins
o
phenformin,
o cyanide,
o
methanol
o
ethanol intoxication in chronic alcoholics,
o anti-retroviral drugs
type B3: Assoc with inborn errors of metabolism
o congenital forms of lactic acidosis with various enzyme
defects eg pyruvate dehydrogenase deficiency

Diagnosis
The condition is often suspected on the history and examination (eg shock, heart
failure) and is confirmed and quantified by measuring the blood lactate level.
Management
The principles of management of patients with lactic acidosis are:
1. Diagnose and correct the underlying condition
2. Restore adequate tissue oxygen delivery; restore adequate perfusion
3. Avoid sodium bicarbonate (except possibly for treatment of associated severe
hyper kalaemia)
4. When the circulation is restored, the liver can metabolise the circulating
lactate.
5. If lactic acidosis is severe and the cause cannot be corrected, the mortality can
be quite high.