2. Content
General points
Maintenance of blood pH
Primary defense – Hco3-, hpo4-2, protein buffers
Respiratory mechanism for pH regulation
Renal mechanism for pH regulation
Acid base disorders
Analysis and clinical evaluation of acid base disorders
3. General points
1. Acids –Bases
2. pH, 7,4 denotes H+ conc of
0.00004mEq/l
3. pH of normal biological fluids
4. Maintenance of blood pH
Normal plasma pH is 7.4
Plasma pH compatible with life varies from 7.7 to 6.9
pH of mixed venous blood is 7.38 compared with 7.41 of arterial blood
pH of ECF is maintained between a narrow range of 7.35 and 7.45
5. Dietary and metabolic production of
acid and bases
Volatile acids
1. Co2
Non volatile acids
1. Sulphuric acid
2. Phosphoric acid
3. Hydrochloric acid
4. Lactic acid
5. Acetic acid and β-hydroxybutyric
acid
6. Uric acid
1. Hco3-
2. NH3
6. Primary line of defense
A buffer is a solution, consisting of a weak acid and its salt with strong
base, which prevents a change in pH when H+ ions are added to or
removed from a solution
Buffers are most effective within 1.0 pH unit of the pK of the buffer
7. Bicarbonate versus nonbicarbonate
buffers
Bicarbonate buffer forms 53% of the buffering in the whole body.
Out of it: Plasma HCO3 − contributes 35%
Erythrocyte HCO− contributes 18%
Nonbicarbonate buffers form remaining 47% of the buffering in the whole
body.
Haemoglobin and oxyhaemoglobin 35%
Plasma proteins 7%
Organic phosphate 3%
Inorganic phosphate 2%
8. Extracellular versus intracellular buffers
Bicarbonate (HCO3 ) is the major
extracellular buffer, which is produced
from CO2 and H2O
Phosphate is a minor extracellular
buffer.
Plasma proteins
Haemoglobin
Organic phosphate-AMP,ADP,
ATP,2.3DPG
Proteins
Hco3-
10. Addition of strong acid, e.g. HCl is followed by buffering of H+
Addition of strong base (e.g. NaOH), results in conversion into a weak base
(NaHCO3 )
11. Phosphate buffer system
In ECF (plasma and interstitial fluid), the HPO4 2− /H2PO4 − buffer exists
in small concentration (0.66 mmol/L) and thus contributes little to the
buffering capacity of plasma
In intracellular fluid (ICF), the HPO4 2− /H2PO4 − forms an important
buffer pair
In renal tubules, the HPO4 2− /H2PO4 − forms an effective extracellular
buffer
12. Organic phosphate buffer system
Organic phosphates (such as AMP, ADP, ATP and 2,3- diphosphoglycerate,
i.e. (2,3-DPG)
They exist in quantitatively significant amount in ICF (8.4 mmol/L)
Giving this compartment the capacity to effectively buffer both
noncarbonic and carbonic acid, as well as alkali.
13. Protein buffer system
The protein buffer system of the blood is constituted by the plasma
proteins and haemoglobin combinedly.
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
14. Plasma proteins buffer system
Plasma proteins buffer system accounts for 15% of the buffering capacity
of the whole blood
Haemoglobin buffer system
Deoxyhaemoglobin (Hb) is a better buffer than oxyhaemoglobin (HbO2 ),
because the imidazole groups of Hb dissociate less than those of HbO2 ,
making Hb a weaker acid
15. Respiratory mechanism of pH
regulation
Second line of defense
Effect of CO2
Effect of pH
Hyperventilation. It occurs in response to metabolic acidosis and results in
lowering of pCO2 to match the decreased (HCO3 − )
Hypoventilation occurs in response to metabolic alkalosis and results in
raising the pCO2 to match the increased (HCO3 − )
16. Renal mechanism for pH regulation
Reabsorption’ of filtered HCO3 −
‘Generation’ of new HCO3 −
H+ excretion in the form of titrable acid and NH4 +
17. Acid base disorders
The simple acid–base disorders
1. Metabolic acidosis
2. Metabolic alkalosis
3. Respiratory acidosis
4. Respiratory alkalosis
Mixed acid–base disorders
1. Metabolic acidosis and respiratory
acidosis
2. Metabolic acidosis and respiratory
alkalosis
3. Metabolic alkalosis and respiratory
alkalosis
4. Metabolic alkalosis and respiratory
acidosis
18. Metabolic acidosis
Metabolic acidosis is either increased net nonvolatile acid load or loss of
base (HCO3 − )
Causes –
1. Addition of nonvolatile acids – DKA, Lactic acidosis,
Methanol/formaldehyde intoxication etc
2. Loss of nonvolatile alkali – Diarrhoea, Type 2 renal tubular acidosis
3. Failure of the kidney to excrete sufficient net acid to replenish HCO3 −
used to titrate the net daily acid load – CRF, Type I distal renal tubular
acidosis
19. Uncompensated metabolic acidosis
It has Low plasma pH and low plasma HCO3 −
Respiratory compensation
Renal compensation
20. Hyperchloraemic versus normochloraemic
metabolic acidosis.
Normochloraemic metabolic acidosis - decreased plasma (HCO3 − ) and
low plasma pH with normal serum Cl − levels – Renal failure
Hyperchloraemic metabolic acidosis - decreased plasma (HCO3 ) and low
plasma pH with an increase in plasma (Cl − ) – Diarrhoea, Type 2 RTA
21. ANION GAP
In normochloraemic metabolic acidosis, the concentration of unmeasured
anions is increased to replace HCO3 – and hence the serum anion gap is
increased – DKA, lactic acidosis etc
In hyperchloraemic metabolic acidosis, the concentration of Cl − is
increased to replace the HCO3 − , so the serum anion gap is normal –
diarrhoea
22. A. Normal ionogram showing the major cations
(Na + ) and the minor cations (K + , Ca 2+ and
Mg 2+ ). The major anions are HCO3 − and Cl −
and the unmeasured anion constitute the anion
gap
B. Simplified ionogram showing Na + as the only
cation and making the anion column fall as the
Na + column
C. Ionogram depicting increased anion gap in
normochloraemic metabolic acidosis
D. ionogram depicting normal anion gap but
increased [Cl − ] in hyperchloraemic metabolic
acidosis
23. Metabolic alkalosis
Metabolic alkalosis is either addition of nonvolatile alkali or loss of H+
from the body
Causes-
1. Addition of nonvolatile alkali – Antacids
2. Volume contraction alkalosis - Haemorrhage Loop or thiazide diuretics
3. Loss of H+ from the body – Vomiting, Hyperaldosteronism
24. Uncompensated metabolic alkalosis
Has high plasma pH and high plasma HCO3 −
Respiratory compensation
Renal compensation
25. Respiratory acidosis
Increased pCO2 , which by mass action causes an increase in H+ and thus
lowers the blood pH
Causes –
1. Inadequate ventilation - Drug-induced, Weakening of respiratory muscles,
Airway obstruction.
2. Impaired gas diffusion – ARDS,COPD
26. Uncompensated respiratory acidosis
low plasma pH and high pCO2
Renal compensation
Acute respiratory acidosis
Because of intracellular buffering, plasma (HCO3 − ) increases 1 mEq/L for
every 10 mm rise in pCO2 during this period
Chronic respiratory acidosis
During this phase, plasma (HCO3 − ) increases 3.5 mEq/L for every 10 mm
rise in pCO2
27. Respiratory alkalosis
Decreased pCO2 associated with low (H+ ) and an elevated plasma pH
Causes –
Pneumonia and pulmonary embolus
High altitude
Psychogenic hyperventilation
Salicylate intoxication.
28. Uncompensated respiratory alkalosis,
Has high plasma pH and low pCO2
Intra cellular compensation
Renal compensation
Acute respiratory alkalosis - plasma (HCO3 − ) decreases 2 mEq/ L for
every 10 mmHg fall in pCO2 .
Chronic respiratory alkalosis - plasma (HCO3 − ) decreases by 5 mEq/L for
every 10 mmHg reduction in pCO2.
29.
30. Analysis and clinical evaluation of
acid– base disorders
Three-step approach
Step I. Estimate pH to know acidosis (pH < 7.4) or alkalosis (pH > 7.4).
Step II. Detect primary disturbance to know whether the disorder is
metabolic (primary disturbance of HCO3 − ) or respiratory (primary
disturbance of pCO2 ).
Step III. Analysis of compensatory response can be done from the values of
plasma HCO3 − and pCO2 .
31.
32. The shaded areas of the
diagram show the 95 per
cent confidence limits for
the normal compensations
to simple metabolic and
respiratory disorders
6-12 hrs and 3-5 days
Ex 1 - pH 7.30, plasma
HCO3 – concentration 12.0
mEq/L, and plasma PCO2
25 mm Hg
Ex 2 - pH 7.15, plasma
HCO3 – concentration 7
mEq/L, and plasma PCO2
50 mm Hg
33. Davenport diagram
Point A, represents uncompensated
respiratory acidosis
Point B, represents uncompensated
respiratory alkalosis
Point C, represents uncompensated
metabolic acidosis
Point D, represents uncompensated
metabolic alkalosis
Point E, represents respiratory acidosis
+ metabolic acidosis
Point F, represents respiratory acidosis
+ metabolic alkalosis
Point G, represents respiratory
alkalosis + metabolic acidosis
Point H, represents respiratory
alkalosis + metabolic alkalosis
