Concepts of acid base balance and its disorders are very important for practice of medicine.It is for the benefit of medical and students of allied fields.

1. Dr.S.Sethupathy, M.D.,Ph.D.,
Professor of Biochemistry,
Rajah Muthiah Medical College,
Annamalai university

2.  Metabolism is the basis of life.
 Metabolism is possible only because of
enzymes.
 Enzyme activity is influenced by pH
 So, maintenance of acid base balance is
crucial for life.

3. 3
 Acids take in with foods
 Acids produced by metabolism of lipids and
proteins
 Cellular metabolism produces CO2.
 CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3
-

4.  Acid is a protein (H+) donor
Eg : HCl H+ + Cl
 Base is a proton (H+) acceptor.
NaOH + HCl NaCl + H2O
 Strong acids completely dissociate
into their constituent ions in solution
eg. HCl
 Weak acids partially dissociate –
lactic acid, carbonic acid

5. 5
 Homeostasis of pH is tightly regulated
 ECF= 7.4
 Blood = 7.35 – 7.45
 < 6.8 or > 8.0 death occurs
 Acidosis (acidemia) below 7.35
 Alkalosis (alkalemia) above 7.45

6.  It is a mixture of weak acid and its salt or
weak base and its salt
 Buffers resist pH change
 Example : Bicarbonate buffer
 NaHCO3 / H2CO3
 Buffering capacity depends on actual
concentrations of salt and acid and its ratio.
 Buffering capacity is maximum in the range of
1 unit ± of its pK value.

9. 9
 Sodium Bicarbonate (NaHCO3) and carbonic
acid (H2CO3)
 Maintain a 20:1 ratio : HCO3
- : H2CO3
HCl + NaHCO3 ↔ H2CO3 + NaCl
NaOH + H2CO3 ↔ NaHCO3 + H2O

10. 10
 Major intracellular buffer
 H+ + HPO4
2- ↔ H2PO4-
 OH- + H2PO4
- ↔ H2O + H2PO4
2-

11. 11
 Includes hemoglobin, proteins in ICF
 Carboxyl group gives up H+
 Amino Group accepts H+
 Some side chains of amino acid residues
can buffer H+ - lysine, arginine, histidine

12.  Weak acids dissociate only partially in the
solution.
 Conjugate base is the unprotonated form of
corresponding acid.
 For example: Cl-, HCO3
-
 Weak acid H2CO3 H+ + HCO3-
 Proton (conjugate
base)
 Conjugate base of weak acid is strong.
 Strong acid
 HCl H+ + Cl- (conjugate base)
 Conjugate base of strong acid is weak.

13.  The dissociation of an acid is a freely
reversible reaction.
 So at equilibrium, the ratio of dissociated
and undissociated particles is constant.
(Ka - dissociation constant)
 Ka = H+ + A- dissociated / HA un
dissociated
 H+ - proton A- - conjugate base or anion

14.  It is the pH at which the acid is half
dissociated.
 It is negative logarithm of acid
dissociation constant Ka to the base
10.
 At pK value, Salt : acid ratio is 1:1.
 pKa = - log 10 Ka

15.  pH = pKa + log 10 ( salt / acid)
 Due to metabolism mainly acids are produced.
 The acids are of two types.
1.Fixed acids or non volatile acids
Eg. phosphoric, sulfuric acids, organic acids
such as pyruvic, lactic, ketoacids.
2.Volatile acid- carbonic acid
 Carbonic acid ,being volatile is eliminated by
lungs as CO2.
 Fixed acids are excreted by kidneys.

16.  pKa of carbonic acid is 6.1.
 pH = 6.1 + log 10 (bicarbonate/ carbonic acid –
0.03 x pa CO2 ) { paCO2- 40mm of Hg}
=6.1 + log 10 (24/1.2)
 = 6.1 + 1.3 = 7.4
 Arterial blood pH = 7.4
 Bicarbonate represents alkali reserve and it is
twenty times more than carbonic acid to ensure
high buffering efficiency.

17.  Histidine residue of hemoglobin can act as acid
or base.
 Histidine has pKa value of 6.5 and it is efficient
buffer .
 Deoxyhemoglobin in tissues accepts H+ ions to
form HHb. (KHb / HHb buffer )
 Oxygenated hemoglobin releases H+ ions in
lungs.
 Amino groups of hemoglobin interact with CO2
to form carbamino hemoglobin.

18.  Action of hemoglobin buffer
 In tissues, CO2 diffuses into erythrocytes to
form carbonic acid by carbonic anhydrase.
 H2O + CO2 H2CO3
 H2CO3 H+ + HCO3
-
 KHb accepts H+ and releases K+ .
 Bicarbonate diffuses into the plasma where its
concentration low.
 To maintain electrical neutrality, Chloride
(Cl- ) enters the erythrocytes.
 This is called chloride shift.

20.  In lungs, oxygenation of haemoglobin
releases H+ which combines with
bicarbonate to form carbonic acid by
carbonic anhydrase.
 Carbonic acid dissociates into water and
CO2.
 CO2 is expired out by lungs.
 Chloride comes out in exchange for
HCO3
- to maintain electrical neutrality.

22.  pH = pKa + log {bicarbonate (metabolic
component)/ carbonic acid-paCO2
(Respiratory component)}
 Respiratory component is maintained by
lungs and Metabolic component is
maintained by kidneys.
 Carbonic acid is a volatile acid so it is
eliminated by lungs.
 The rate of respiration is controlled by the
chemoreceptors in the respiratory centre which
are sensitive to pH change of blood.

23. Functions
 Reabsorption of bicarbonate involves the
reabsorption of bicarbonate filtered without
excretion of H+ ions.
 Excretion of H+ ions
 Here there is net gain of bicarbonate for each
H+ excretion. As the H+ ion excretion increases,
the excretion of H+ against concentration
gradient becomes difficult.
 So in the distal convoluted tubules, urinary
buffers buffer the free H+ ions.

26.  Two important urinary buffers are
1. Phosphate buffer
2. Ammonia
 The maximum limit of acidification of urine is
4.5.
 Normally 70 meq acid is excreted daily. In
metabolic acidosis, this can raise to 400
meq/day.

35. Term Symbol Normal value Range Unit
H+ H+ 40 36-44 nmol/L
pH pH 7.4 7.36-7.44 -
CO2 tension PaCO2 40 36-44 mm Hg
Base exces BE 0 –2 to +2 mmol/L
Total CO2 TCO2 25 23-27 mmol/L
Actual HCO3 HCO3 24 22-26 mmol/L
Standard HCO3 SBC 24 22-26 mmol/L
O2 saturation SaO2 98 95-100 %
O2 tension PaO2 95 80-100 mmHg

36. 36
 If underlying problem is metabolic,
hyperventilation or hypoventilation
can help : respiratory compensation.
 If problem is respiratory, renal
mechanisms can bring about
metabolic compensation.

37. 37
 Principal effect of acidosis is depression of the CNS
through ↓ in synaptic transmission.
 Generalized weakness
 Deranged CNS function the greatest threat
 Severe acidosis causes
 Disorientation
 coma
 death

38. 38
 Alkalosis causes over excitability of the central
and peripheral nervous systems.
 Numbness
 Lightheadedness
 It can cause :
 Nervousness
 muscle spasms or tetany
 Convulsions
 Loss of consciousness
 Death

42.  HCO3– level is 24 mEq/L
 The normal range is 22-26.
 When HCO3– level falls below 22 mEq/L (in
conditions like acute watery diarrhea, renal
tubular acidosis, addition of lactic acid and
ketoacids) metabolic acidosis results.
 When the HCO3– levels exceeds 26 mEq/L (in
conditions like persistent vomiting, increased
renin-angiotensin activity, loop diuretics) it is
termed as metabolic alkalosis.
 Kidney regulates HCO3– homeostasis.

43. It can be due to 1.Increased acid production
2. Decreased removal of acids by kidneys (renal
failure)
3.loss of bicarbonate
Increased acid production: The causes are lactic
acidosis in shock, septicemia, ketoacidosis in Von
Gierkes’s disease, diabetes mellitus and
starvation.
Loss of bicarbonate due to diarrhoea
(gastroenteritis).

46.  In severe acidosis when pH falls below 7.20 (H+ ion
concentration >63 nEq/L), grave features like poor
myocardial performance, arrhythmias, hypotension,
pulmonary edema and hyperkalemia occur.
 Similarly in severe alkalosis when the pH exceeds 7.5
(H+ ion concentration <28 nEq/L) features like mental
confusion, muscular irritability, seizures, arrhythmias,
generalized tissue hypoxia and hypokalemia occur.
 Identification of these clinical features is difficult in a
sick child presenting pre-dominantly with the features of
primary disease.
 Normal hydrogen ion concentration in our body is 40
nmol/l and the acceptable range is 36-44 nmol/L.

47. Anion Gap
 It is a measure of unmeasured anions
 A small amount of anion that cannot be
measured by biochemical investigations is
named as anion gap:
 (Na+ + K+) = (Cl– + HCO3–) + AG
 (Unmeasured anions) (Anion gap)
 (135 + 04) = (100 + 24) + other anions
 Anion gap = 8-16 mmol/L
 High anion gap acidosis (HAGMA)
 Normal anion gap acidosis (NAGMA)

50. Increased anion gap
(Normochloremic acidosis)
Normal anion gap (Hyperchloremic
acidosis)
Lactic acidosis Diarrhea
Shock Rental tubular acidosis
Asphyxia Uretero sigmoidostomy
Cyanide Poisoning Parenteral alimentation
Salicylate poisoning Rapid ECF expansion
Paraldehyde poisoning Exogenous chlorides
Biguanides poisoning CaCl2, MgCl2, NH4Cl
Organic acidemias Cholestyramine
Inborn errors of carbohydrate and Carbolic anhydrase inhibitors
pyruvate metabolism Small bowel/biliary fistula
Ketoacids
Diabetes mellitus
Starvation
Sulphuric/phosphoric acids
Renal failure

51. Metabolic
acidosis (HCO3)
For every 1 mEq/L fall
in HCO3 PaCO2
should fall by 1 mm of
Hg (1-1.5)
Metabolic
alkalosis (HCO3)
For every 1 mEq/L
increase HCO3–
paCO2 should increase
by 1 mm of Hg (0.5-1)

52.  Normal PaCO2 value - 40 mm Hg (5.3K Pa) - 36-44 mm Hg.
 PaCO2 above >44 mm Hg respiratory acidemia due to
ventilatory failure
 Decrease of PCO2 (<36 mm Hg) due to respiratory alkalosis.
 95% ofCO2 produced is transported by the RBC
 5% by plasma in dissolved (dCO2) and 0.1% as chemically
dissolved (carbonic acid).
 The total CO2 (TCO2 ) includes dCO2 and H2CO3.
 For every 20 mm of Hg increase of PaCO2, pH falls by 0.1
unit
 For every 10 mm of Hg fall of PaCO2, pH increases by 0.1.

53. Failure of ventilation :
 Depression of respiratory centre due to
disease or drug-induced respiratory
depression, head injury.
 Paralysis of muscles (eg, myasthenia gravis,
muscular dystrophy)
 Airway obstruction- foreign body –trachea ,
asthma or chronic obstructive pulmonary
disease (COPD).
 Obesity hypoventilation syndrome

54.  The biochemical findings are:
 pH < 7.35
 paCO2 > 45 mm of Hg (Hypercapnia).
 Renal compensation occurs in 3-5 days.
compensatory metabolic alkalosis.
 Acute respiratory acidosis
 1mmol increase- for every 10 mm of Hg
PaCO2
 Chronic respiratory acidosis, 3.5 mmol of
bicarbonate for every 10mmof Hg PaCO2

55.  It is caused by hyperventilation. The causes for
hyperventilation are: Anxiety, salicylate poisoning
, artificial ventilation and pulmonary embolism.
 The biochemical findings are
 pH is increased > 7.45
 paCO2 is decreased < 35 mm of Hg
 Bicarbonate is normal in uncompensated
condition.
 In compensatory metabolic acidosis, bicarbonate
will be decreased. Kidney responds to decrease in
paCO2 and excretes more bicarbonate.

56. 56
 Conditions that stimulate respiratory center:
 Oxygen deficiency at high altitudes
 Pulmonary disease and Congestive heart failure –
caused by hypoxia
 Acute anxiety ,Fever, anemia
 Early salicylate intoxication
 Cirrhosis, Gram-negative sepsis

57. 57
 Mechanism: Renal loss of bicarbonate causes a
further fall in plasma bicarbonate (in addition
to the acute drop due to the physicochemical
effect and protein buffering).
 Magnitude: An average 5 mmol/l decrease in
[HCO3-] per 10mmHg decrease in pCO2 from
the reference value of 40mmHg. This maximal
response takes 2 to 3 days to reach.
 Limit: The limit of compensation is a [HCO3-]
of 12 to 15 mmol/l.

58. 58
1. Note whether the pH is low (acidosis) or high
(alkalosis)
2. Decide which value, pCO2 or HCO3
- , is
outside the normal range and could be the
cause of the problem. If the cause is a change
in pCO2, the problem is respiratory. If the
cause is HCO3
- the problem is metabolic.

59. 59
3. Look at the value that doesn’t correspond to the
observed pH change. If it is inside the normal
range, there is no compensation occurring. If it
is outside the normal range, the body is
partially compensating for the problem.
 A patient is in intensive care because he
suffered a severe myocardial infarction 3 days
ago. The lab reports the following values from
an arterial blood sample:
 pH 7.3
 HCO3- = 20 mEq / L ( 22 - 26)
 pCO2 = 32 mm Hg (35 - 45)

60. 60
 Metabolic acidosis
 With compensation

65.  Predicted pCO2 = 1.5 x HCO3 + 8 ± 2
 ( measured bicarbnate)
 Measured pCO2 = Predicred pCO2
(Pure Metabolic acidosis )
 Measured pCO2 > Predicred pCO2
 (Metabolic acidosis & Respiratory acidosis)
 Measured pCO2 < Predicred pCO2
 (Metabolic acidosis & Respiratory alkalosis)

66.  pH: 7.35 – 7.45
 PCO2:
 Males: 35 – 48 mm Hg
 Females: 32 – 45 mm Hg
 HCO3: 22 – 27 mEq/L
 Base Excess:
 New born (0 – 7 days): -10 to -2 mmol/L
 Infant (1 week – 1 year): -7 to –1 mmol/L
 Child (1 – 16 years): -4 to +2 mmol/L
 Adult (>16 years): -3 to +3 m

67.  Warm the area for 3-10 mins not > than 420C –
arterialization - 0.2 ml
 Lithium heparin – fill 2 capillary tubes without
air bubble –cap both ends
 Within 15 mins – analyze
 > 30 mins , clotted sample – discard
 Critical values
 pCO2: < 15 and > 70 mm Hg
 pH: < 7.2 and > 7.6

68. Thank you