Acid and Base

1. ACID-BASE BIOCHEMISTRY
200 LEVEL CBD/IBS PROGRAMME
DR. A.Z LAWAL

2. Objectives
 Definition of terms( Acid, Base and pH)
 Method of measuring pH
 Sources of acid
 Physiological PH
 Hydrogen ion Homeostasis
 Clinical importance

3. Definitions of an acid
1. Taste
2. Boyle
3. Arrhenius
4. Bronsted-Lowry
5. Lewis

4. Neutralization:
 Acid release H+ into solution and bases release OH-. When mix together an
acid and base , the H+ ion would combine with the OH- ion to make the
molecule H2O, or plain water:
H+
(aq) + OH-
(aq) → H2O
 The Neutralization reaction of an acid with a base will always produce water
and a salt: HCl + NaOH → H2O + NaCl

5. pH
 Both acids and bases are related to the concentration of hydrogen ions
present.
 Acids increase the concentration of hydrogen ions, while bases decrease the
concentration of hydrogen ions (by accepting them).
 The acidity or basicity of something therefore can be measured by its
hydrogen ion concentration.

6. PH Scale
 PH scale was invented In 1909, by the Danish biochemist Sören Sörensen for
measuring acidity.
 The pH scale is described by the formula: pH = -log [H+]
 Note: concentration is commonly abbreviated by using square brackets, thus
[H+] = hydrogen ion concentration. When measuring PH, [H+] is in units of
moles of H+ per litre of solution.

7. Henderson-Hasselbalch equation,
 A simple expression that relates Pka, PH and Buffers concentration
 Important for understanding buffer action and acid-base balance in the blood
and tissues of vertebrates.
 A useful way of restating the expression for the dissociation constant of an
acid.
 For the dissociation of a weak acid HA into H and A, the Henderson-
Hasselbalch equation can be derived as follows:

8. METHODS of measuring PH
 PH Electrode
 Carbon dioxide electrode
 Oxygen electrode
 Laboratory measurement of bicarbonate
 Ion selective electrodes for K+ Na+ Cl-

9. Physiological PH
 Extracellular fluid ; pH 7.35 – 7.46 (35-45 nmol/L)
 Digestive tract
Gastric Juice 1.0-3.0
Pancreatic Juice 8.0-8.3
 Intercellular organelles;
Lysosomal pH 4-5
Digestive and lysosomal enzymes function optimally at these pH ranges

10. Sources of acid
 Acid production from metabolism of food
 Sulphuric acid from metabolism of sulphur-containing amino acids of proteins
 Lactic acid from sugars
 Ketoacids from fats
 Acid production from metabolism of drugs
 Direct metabolism of drug to more acidic compound eg salicylates urates etc
 Induction of enzymes which metabolise other compounds (endogenous or
exogenous) to acids

11. Sources of acid cont.
 Inborn errors of metabolism
 Organic acid disorders
 Lactic acidosis
Greatest potential source of acid
Carbon dioxide
(1) CO2 + H2O <=> H2CO3
(2) H2CO3 <=> H+ + HCO3
-
Potentially 15,000 mmol/24 hours

12. Hydrogen ion homeostasis
 1. Buffering
 2. Excretion

13. Buffering
 As hydrogen ions are produced, they are buffered – limiting the rise in [H+]
 Buffer solutions consist of a weak acid and its conjugate base
 As hydrogen ions are added some will combine with the conjugate base and convert it
to undissociated acid
 Bicarbonate – carbonic acid buffer system
H+ + HCO3
- <=> H2CO3
 Addition of H+ drives reaction to the right
Conversely
 Fall in H+ drives reaction to the left as carbonic acid dissociates producing more H+

14. Buffering cont.
 Buffering systems in blood
 Bicarbonate ions-most important
 Proteins including intracellular proteins
 Haemoglobin
 Buffer solutions operate most efficiently at [H+] that result in approximately
equal concentration of undissociated acid and conjugate base
 But at normal extracellular fluid pH
[H2CO3]  1.2 mmol
whereas [HCO3
-] is twenty times greater

15. Buffering cont.
 The bicarbonate system is enhanced by the fact that carbonic acid can be
formed from CO2 or disposed of by conversion to CO2
CO2 + H2O <=> H2CO3
 For every hydrogen ion buffered by bicarbonate – a bicarbonate ion is
consumed.
 To maintain the capacity of the buffer system, the bicarbonate must be
regenerated
 However, when bicarbonate is formed from carbonic acid (CO2 and H2O)
equimolar amounts of [H+] are formed

16. Excretion
 Bicarbonate formation can only continue if these hydrogen ions are removed
 This process occurs in the cells of the renal tubules where hydrogen ions are
secreted into the urine and where bicarbonate is generated and retained in
the body
Two different processes;
 Bicarbonate regeneration (incorrectly reabsorption)
 Hydrogen ion excretion

17. Excretion cont.
Importance of Renal Bicarbonate Regeneration
 Bicarbonate is freely filtered through the glomerulus so plasma and
glomerular filtrate have the same bicarbonate concentration
 At normal GFR approx 4300 mmol of bicarbonate would be filtered in 24 hr
 Without re-generation of bicarbonate the buffering capacity of the body
would be depleted causing acidotic state
 In health virtually all the filtered bicarbonate is recovered

18. ► Carbon dioxide transport
► Carbon dioxide produced by aerobic respiration diffuses out of cells and into
the ECF
► A small amount combines with water to form carbonic acid decreasing the pH
of ECF
► In red blood cells metabolism is anaerobic and very little CO2 is produced
hence it diffuses into red cells down a concentration gradient to form
carbonic acid (carbonate dehydratase) buffered by haemoglobin .

19. ► Haemoglobin has greatest buffering capacity when it is dexoygenated hence
the buffering capacity increases as oxygen is lost to the tissues
► Net effect is that carbon dioxide is converted to bicarbonate in red cells
► Bicarbonate diffuses out of red cells down concentration gradient and
chloride ions diffuse in to maintain electrochemical neutrality (chloride shift)

21.  In the lungs this process is reversed
 Haemoglobin is oxygenated reducing its buffering capacity and generating
hydrogen ions
 These combine with bicarbonate to form CO2 which diffuses into the alveoli
 Bicarbonate diffuses into the cells from the plasma

22.  The hydrogen ion concentration of plasma is directly proportional to the PCO2 and inversely
proportional to bicarbonate
[H+] = k pCO2/[HCO3
-]
[H+] in nmoles/L, [HCO3
-] in mmoles/L
pCO2 in kPa k = 180
pCO2 in mm Hg k= 24
 Possible to use the equation to calculate the bicarbonate concentration from the pCO2 and pH (blood
gas analysers)
 The relationship between [H+], pCO2 and bicarbonate fundamental to understanding pathophysiology
of hydrogen ion homeostasis

23. Clinical importance
Four Components to acid-base disorders
 Generation
 Buffering
 Compensation
 Correction
Occurring concurrently

24. Clinical importance cont.
Classification of acid-base disorders
► Acidosis ;
[H+] above normal, pH below normal
► Alkalosis;
[H+] below normal, pH above normal

25. Clinical importance cont.
 Further classified as
 Respiratory
 Non-respiratory (metabolic)
 Mixed – difficult to distinguish between primary mixed condition and compensated
disorder
 Respiratory disorders involve a change in pCO2
 Metabolic disorders involve change in production or excretion of hydrogen
ions or both
 Non-respiratory acidosis; Increased production/reduced excretion of acid

26.  Overproduction of acid
 Keto acidosis (diabetes, starvation, alcohol)
 Lactic acidosis (inherited metabolic defect or drugs)
 Inherited organic acidoses
 Poisoning (salicylate, ethylene glycol, alcohol)
 Excessive parenteral amino acids
 Reduced excretion of acid
 Generalised renal failure
 Renal tubular acidosis
 Carbonate dehydratase inhibitors
► Loss of Bicarbonate
 Diarrhoea
 Pancreatic, intestinal, biliary fistula or drainage

27.  Compensation of non-respiratory acidosis
Excess hydrogen ions are buffered by bicarbonate forming carbonic acid which dissociates to
carbon dioxide to be lost in expired air
 The buffering limits the rise in [H+] at the expense of reduction in bicarbonate
o Hyperventilation increases removal of CO2
lowering pCO2
o PCO2 / [HCO3
-] ratio falls reducing [H+]
o Hyperventilation is the direct result of increased [H+] stimulating the respiratory centre
(Kussmaul respiration)
Limitations
 Respiratory compensation cannot completely normalise the [H+] because the
hyperventilation is stimulated by the increase in [H+] and as this falls the drive on the
respiratory centre is reduced
 Increased work of respiratory muscles during hyperventilation produces CO2 limiting the
degree to which PCO2 can be lowered

28.  The degree of compensation may be limited further if respiratory function is
compromised
 If it is not possible to correct the cause of the acidosis may get a new steady
state of chronic acidosis
 [H+] [HCO3
-] and ↓PCO2
 If renal function is normal excess [H+] can be excreted by the kidneys
Summary of non-respiratory acidosis
 pH 
 [H+] 
 PCO2 
 [HCO3
-]  

30. Non respiratory alkalosis
 Characterised by primary increase in ECF bicarbonate
 Consequent reduction in [H+]
 Normally increase in bicarbonate causes reduction in renal bicarbonate regeneration
and increased urinary excretion of bicarbonate
Causes;
 Loss of un-buffered hydrogen ions
Gastrointestinal
- vomiting with pyloric stenosis
- diarrhoea
- nasogastric aspiration

31. Non respiratory alkalosis
 Renal causes
Mineralocorticoid excess
Conn’s syndrome
Cushings syndrome
Drugs with mineralocorticoid activity
Diuretic therapy (not K+ sparing)
 Administration of alkali
 Over-treatment of acidosis
 Chronic alkali ingestion (antacids)

32. Non respiratory alkalosis
 Maintenance requires inappropriate renal bicarbonate reabsorption/regeneration
- decrease in ECF volume (hypovolaemia)
- mineralocorticoid excess
- potassium depletion
 Hypovolaemia
 Increased stimulus to sodium reabsorption
 Dependant on adequate anions
 If chloride deficient (GI losses) electrochemical neutrality during Na+ absorption maintained by increased bicarbonate
absorption and by H+ and K+ excretion

33.  Mineralocorticoid excess
 Alkalosis perpetuated by increased hydrogen ion excretion secondary to increased
sodium reabsorption
Potassium depletion
Potassium and hydrogen ion excretion compete for exchange with sodium so depletion of
potassium causes increased H+ excretion
Compensation
 Low H+ inhibits the respiratory centre causing
hypoventilation and increase in PCO2
 Self- limiting as increase in PCO2 increases drive on
respiratory centre
 In chronic state development of reduced sensitivity to PCO2
– more significant compensation BUT
 Hypoventilation causing hypoxaemia will provide stimulation
of RC and prevent further compensation

34. Summary of non respiratory alkalosis
 [H+] 
 pH 
 PCO2 
 [HCO3
-]  
Respiratory alkalosis
 Characterised by reduction in PCO2
 Reduces the PCO2/ [HCO3
-] ratio
For every KPa decrease in PCO2
 decrease in [H+] 5.5 nmol/L
 Small decrease in bicarbonate


35.  Hypoxia
 High altitude
 Severe anaemia
 Pulmonary disease
 Increased respiratory drive
 Stimulants eg salicylates
 Cerebral – trauma, infection, tumours
 Hepatic failure
 Pulmonary disease
- Pulmonary oedema
- Pulmonary embolism
Mechanical over-ventilation

36. Compensation
 reduction in renal hydrogen ion excretion
Develops slowly maximal in 36-72 hours
Mixed acid base disorders;
 respiratory alkalosis with metabolic acidosis
e.g. salicylate poisoning causes respiratory alkalosis by directly stimulating the
hypothalamic respiratory centre causing over-breathing and increased
excretion of CO2
Salicylate metabolised to acids

37. Interpretation of result
 Reference ranges
 pH 7.35 – 7.46
 [H+] 35-45 nmol/L
 pCO2 4.5-6.0 kPa (35-46 mm Hg)
 pO2 11-15 kPa (85-105 mm Hg)
 Total Bicarbonate (CO2) 22-30 mmol/L