Acid base balance and disorders

1. Acid Base
Balance and Disorders
Dr Jemil Makadia

2. pH
• pH in body maintained in very narrow range
• Plasma/blood- 7.4
• Intracellular- 7
• Importance of pH maintenance
• Enzymes, transport molecule, membrane, nucleic acid
• pH= -Log [H+] = log 1/[H+]
• Change in pH by 1 leads to change in [H+] by 10 times
• pH range- 0-14
• Acid- liberate proton
• Base- Accept proton

3. Acid-Base
• HA H+ + A-
• Keq = [H+][A-]/[HA] = Ka (dissociation constant)
• Strong acid
• HCl, HNO3, H2SO4
• Liberate more H+
• Ka is more
• Weak acid
• H2CO3, CH3COOH
• Liberate less H+
• Ka is less

4. • pK = - log Ka
• Conjugate Base
• HA H+ + A-
(Acid) (Conjugate base)
Strong Weak
Weak Strong
Weak Acid
Strong Acid
High
Low
pH
Low
High
Ka
High
Low
pK

5. • Polyprotic Acid
• Acids which give more than one proton
• More than one Ka value
• H2CO3
K1 H+ + HCO3
- K2 H+ + CO3
-2
• Base
• Proton acceptors
• NH3
+, OH-, H2O
• Conjugated acid
• Kb, pKb
• NH3
+ + H2O NH4OH NH4
+ + OH-
(Base) (Conj. Acid)

6. - Groups acting as bases
- NH2, NH3
+
- COO-
- HCO3
-
- HPO4
-
-H2PO4
-
- Alkali- NaOH, KOH
Weak Base
Strong Base
Low
High
pH
Low
High
Kb
High
Low
pKb

7. Buffer
• Buffer is a system that resist any alteration in its pH when a
small amount of acid or alkali is added to it.
• Most effective when two components are present in
equimolar concentration. When pH = pK’
• Buffer remains effective when pH is within range of pK’ ± 1
• HA H+ + A-
(acid) (Base)
• Acid (H+) added
• H+ + A- HA

8. • Alkali (OH-) added
• OH- + HA A- + H2O

9. Titration curve
pH
pK Buffer zone
Base

10. Henderson Hasselbalch Equation
• HA H+ + A-
• K’ = [H+][A-]/[HA]
• [H+] = K’ [HA] / [A-]
• - log [H+] = - log K’ - log [HA] / [A-]
• pH = pK’ + log [A-]/[HA]

11. Major Body Buffers
• Cellular metabolism
• Generate acids
• First line of defence
• Bicarbonate buffer
• Phosphate buffer
• Proteins

12. Bicarbonate Buffer
• Major extracellular buffer
• Base- HCO3
- (Bicarbonate)------ Kidney
• Acid- H2CO3 (Carbonic acid)----- Lung
• More Acid (H+) CA
• H+ + HCO3
- H2CO3 H2O + CO2
• More base (OH-)
• OH- + H2CO3 H2O + HCO3
-
• Normal H2CO3/HCO3
-
• 1/20

13. Phosphate Buffer
• Major intracellular buffer
• pK’ = 6.86 (normal intracellular pH- 7)
• H2PO4
- (Acid)
• HPO4
-2 (Base)
• H2PO4
- HPO4
-2 + H+

14. Proteins/Acetate/Ammonium
• Amino acid
• Histidine (Imidazole group)
• pK’ = 6
• Most of buffering capacity of blood is due to Hb
• Next is plasma proteins
• Due to high content of histidine
• High conc. of 12-16 gm/dl
• Intracellular fluid proteins serve as major
buffers
Acetate buffer pK’- 4.76
Ammonium buffer pK’- 9.25 not effective

15. Acid-Base Balance
• Range of pH= 7.35 – 7.45
• Intracellular pH- 7
• Deviation from pH
• Disrupt structural and function of proteins
• Enzymes
• Nucleic acids
• Cell membrane

16. • Three tier defence
• Body metabolism
• H2O + CO2 H2CO3
1. Buffers
2. Lungs
3. Kidneys
1. Buffers
• First line of defence (Bicarbonate buffer)

17. 2. Pulmonary ventilation
• Start in few hours
• CO2 (Acidic)
• Regulated by negative feedback
• pH Chemoreceptor Respiration
3. Renal
• Start in few days
• Final defence
• Generate HCO3
-

18. Mechanism to control bicarbonate level
1. Carbonate dehydratase system
2. Kidney in bicarbonate homeostasis
• Reclamation
• New generation
3. Urinary buffers
4. Role of erythrocytes

19. Carbonate Dehydratase System
• Renal tubular cells
• RBC
• Gastric parietal cells
• H+ + HCO3
- H2CO3 CA H2O + CO2
• CA= carbonic anhydrase
• For each H+ removed from the cell, one bicarbonate ion is
generated.

20. Bicarbonate homeostasis by Kidney
• Done by
• Bicarbonate reclamation
• New bicarbonate generation
1. Bicarbonate reclamation
• Proximal tubular cell (PCT)
• Na+ - H+ antiport system

22. • HCO3
- moves out because
• HCO3
- conc. Inside cells
• Electric potential
• Impermeability of the luminal membrane for HCO3
-
Loss of H+
Na+ is preserved
2. New Bicarbonate Generation
• DCT and Collecting ducts
• H+ secretion is associated with new bicarbonate
generation
• alkali reserve of the body

24. Urinary Buffers
• H+ secretion into tubular lumen
• Acidification of urine [minimum pH = 4.5]
• High conc. gradient
• Prevent further secretion H+
• H+ taken up by luminal buffer system
• Phosphate buffer (Most imp)
• Ammonia (from renal tubular cells)
Excretion of
30-40
mmol of
hydrogen
ion daily

25. • Phosphate (pK’ = 6.8)

27. Role of Erythrocytes

28. Acid-Base Disorders
• Classified on the basis of Bicarbonate-Carbonic acid
• pH = pK’ + log [base]/[acid]
pK’ = 6.1 (for carbonic acid)
Acid = [CO2] = [pCO2 x 0.23]
Base = [HCO3
-]
• pH = 6.1 + log [HCO3
-]/[pCO2 x 0.23]

29. Classification
Metabolic /
Respiratory
Primary component
Acidosis / Alkalosis
Metabolic
HCO3
-
Acidosis
Respiratory
pCO2
Metabolic
HCO3
-
Alkalosis
Respiratory
pCO2

30. Metabolic Acidosis
• (HCO3
-/pCO2)
• Causes
• Excessive production of organic acid
• Normal process produce acid in small quantity
• Bicarbonate deficit
• Acute
• Lactic acidosis
• Due to anaerobic glycolysis
• Intense muscular exercise

31. • Ketoacidosis
• Due to Increase ketone bodies
• Starvation
• DM (DKA)
• Chronic
• PKU
• Hyperammonaemia
• Maple syrup urine disease
• Excessive loss of HCO3
- from the body
• Due to duodenal fluid
• Intestinal fistula
• Severe diarrhoea

32. • Generalized renal tubular dysfunction
• Poisoning
• Methanol poisoning
• Ethylene glycol poisoning
• Increase in Cl- ion
• RTA (Renal Tubular Acidosis)
• Acetazolamide

33. • Compensation (Respiratory)
• (HCO3
-/pCO2)
• Hyperventilation
• pCO2
• (HCO3
-/pCO2)
• Normal pH

34. • Incomplete
• No new HCO3
-
• Acid metabolite is still present then Renal mechanism

35. Anion gap
• It is discrepancy between the measured electrolytes
• ([Na+] + [K+]) – ([Cl-] + [HCO3
-])
= (140+4) – (100+24)
= 20 mmol/L
• Normal value- 16-20
• Represent unmeasured net negative charge on plasma
proteins

36. • High anion gap
• Excessive production of acids
• Unaffected Cl-
• Decrease HCO3
-
• Normal anion gap
• RTA
• Acetazolamide
• Increase Cl-
• Decrease HCO3
-

37. Respiratory Acidosis
• Decrease alveolar ventilation
• pCO2 (Primary)
• pH

38. • Causes
• Airway obstruction
• Asthma
• COPD
• Pulmonary disease
-RDS -Pneumonia
• Thoracic disease
• Kyphoscoliosis
• Flail chest due to Brocken ribs
• Respiratory centre depression
• General anaesthesia
• Tetanus
• Neurotoxins

40. Metabolic Alkalosis
• Body’s defence against alkalosis are less effective due to little
capacity to buffer the OH-
• Very less common
• Due to increase HCO3
-
• Compensation
• (HCO3
-/pCO2)
• Depression of respiratory center
• pCO2

41. • Causes
• Excessive renal generation of HCO3
-
• Competition between K+ and H+ for secretion
• So if hypokalaemia
• H+ secretion
• HCO3
- generation
• pH

42. • Loop diuretics (Furosemide)
• Inhibit pumping of sodium in the loop of Henle
• Increase Na+ load on DCT
• Increase Na+-K+/H+ exchange
• Increase HCO3
- generation
• Alkalosis

43. • Pyloric stenosis
• Excessive loss of H+ and Cl- due to vomiting
• HCO3
- moves into systemic circulation -> increase pH
• Prevent loss of alkaline duodenum content
• Hypovolemia -> alkalosis

44. • Hypovolemia
• Leads to increase aldosterone
• K+ loss from the urine
• Hypokalaemia
• Alkalosis
• Alkali ingestion
• Treatment of acidosis
• Treatment of gastritis

45. Respiratory Alkalosis
• Decrease pCO2 leads to alkalosis
• Causes
• Hyperventilation from
• Tissue hypoxia
• High altitude
• Anaemia
• Hysterical over breathing
• Assisted breathing
• Encephalitis
• Head injury

46. • Compensation
• Decrease HCO3
- generation in kidney
• Decrease CA activity in kidney and RBC so decrease HCO3
-

47. 9
8
7
6
5
4
3
2
1
7.0
7.1
7. 55
7.36
7.0
7.43
7.2
7.51
7.55
pH (7.35-7.45)
16
35
25
15
12
30
29
18
32
HCO3
-
(22-26
mmol/L)
55
60
22
18
43
60
60
20
55
pCO2 (35-45
mmHg)

48. 9
8
7
6
5
4
3
2
1
7.0
7.1
7. 55
7.36
7.0
7.43
7.2
7.51
7.55
pH (7.35-7.45)
16
35
25
15
12
30
29
18
32
HCO3
-
(22-26
mmol/L)
55
60
22
18
43
60
60
20
55
pCO2 (35-45
mmHg)
M Alk
R C

49. 9
8
7
6
5
4
3
2
1
7.0
7.1
7. 55
7.36
7.0
7.43
7.2
7.51
7.55
pH (7.35-7.45)
16
35
25
15
12
30
29
18
32
HCO3
-
(22-26
mmol/L)
55
60
22
18
43
60
60
20
55
pCO2 (35-45
mmHg)
R Alk
M C
M Alk
R C

50. 9
8
7
6
5
4
3
2
1
7.0
7.1
7. 55
7.36
7.0
7.43
7.2
7.51
7.55
pH (7.35-7.45)
16
35
25
15
12
30
29
18
32
HCO3
-
(22-26
mmol/L)
55
60
22
18
43
60
60
20
55
pCO2 (35-45
mmHg)
R Ac
M C
R Alk
M C
M Alk
R C

51. 9
8
7
6
5
4
3
2
1
7.0
7.1
7. 55
7.36
7.0
7.43
7.2
7.51
7.55
pH (7.35-7.45)
16
35
25
15
12
30
29
18
32
HCO3
-
(22-26
mmol/L)
55
60
22
18
43
60
60
20
55
pCO2 (35-45
mmHg)
C M
Alk
R Ac
M C
R Alk
M C
M Alk
R C

52. 9
8
7
6
5
4
3
2
1
7.0
7.1
7. 55
7.36
7.0
7.43
7.2
7.51
7.55
pH (7.35-7.45)
16
35
25
15
12
30
29
18
32
HCO3
-
(22-26
mmol/L)
55
60
22
18
43
60
60
20
55
pCO2 (35-45
mmHg)
NonC
m Ac
C M
Alk
R Ac
M C
R Alk
M C
M Alk
R C

53. 9
8
7
6
5
4
3
2
1
7.0
7.1
7. 55
7.36
7.0
7.43
7.2
7.51
7.55
pH (7.35-7.45)
16
35
25
15
12
30
29
18
32
HCO3
-
(22-26
mmol/L)
55
60
22
18
43
60
60
20
55
pCO2 (35-45
mmHg)
C M
Ac
NonC
m Ac
C M
Alk
R Ac
M C
R Alk
M C
M Alk
R C

54. 9
8
7
6
5
4
3
2
1
7.0
7.1
7. 55
7.36
7.0
7.43
7.2
7.51
7.55
pH (7.35-7.45)
16
35
25
15
12
30
29
18
32
HCO3
-
(22-26
mmol/L)
55
60
22
18
43
60
60
20
55
pCO2 (35-45
mmHg)
NonC
R Alk
C M
Ac
NonC
m Ac
C M
Alk
R Ac
M C
R Alk
M C
M Alk
R C

55. 9
8
7
6
5
4
3
2
1
7.0
7.1
7. 55
7.36
7.0
7.43
7.2
7.51
7.55
pH (7.35-7.45)
16
35
25
15
12
30
29
18
32
HCO3
-
(22-26
mmol/L)
55
60
22
18
43
60
60
20
55
pCO2 (35-45
mmHg)
R Ac
M C
NonC
R Alk
C M
Ac
NonC
m Ac
C M
Alk
R Ac
M C
R Alk
M C
M Alk
R C

56. 9
8
7
6
5
4
3
2
1
7.0
7.1
7. 55
7.36
7.0
7.43
7.2
7.51
7.55
pH (7.35-7.45)
16
35
25
15
12
30
29
18
32
HCO3
-
(22-26
mmol/L)
55
60
22
18
43
60
60
20
55
pCO2 (35-45
mmHg)
M R
Ac
R Ac
M C
NonC
R Alk
C M
Ac
NonC
m Ac
C M
Alk
R Ac
M C
R Alk
M C
M Alk
R C