2. Concept of Acid & base.
pH and H ion concentration.
Handerson-Hasselbalch equation.
What is Acid Base Balance
Mechanisms to maintain acid base balance.
Applied aspects.
Agenda
3. Any compound which forms H+ ions in solution(proton
donors) eg: Carbonic acid releases H+ ions.
Strong acids ? HCL, H2SO4
Weak acids ? H2CO3
ACIDS
4. 1. Volatile Acids:
Can leave the solution and enter the
environment.
H2CO3 is the only volatile acid in the body.
2. Non-Volatile Acids (Fixed Acids/Metabolic Acids):
Acids that do not leave the solution.
All other acids in the body.
Ex: Pyruvic acid, Lactic acid, Phosphoric acid etc.
H2CO3 H2O + CO2
ACIDS – Types of Acids in Body
5. Any compound which combines with H+ ions in solution(proton
acceptors)
Physiologically important bases:
Bicarbonate (HCO3
-)
Biphosphate (HPO4)
OH- +H+ H2O
BASE
eg: Bicarbonate(HCO3
- ) accepts H+ ions
6. pH
Normal pH :7.35-7.45
pH = - log [H+]
Different compartment of human body has specific pH.
pH has role in Enzyme activity.
7. pH – Effects of Abnormal pH
Acidosis
Physiological state resulting from abnormally low plasma pH
Alkalosis
Physiological state resulting from abnormally high plasma pH
plasma pH> 7.45
plasma pH< 7.35
ACIDOSIS ALKALOSIS
NORMAL
DEATH DEATH
Venous
Blood
Arterial
Blood
7.3 7.4 7.5
6.8 8.0
**pH of the ECF is regulated very precisely
8. pH changes have dramatic effects on normal cell function
pH – Effects of ph Change
Changes in excitability of nerve and muscle cells
Influences enzyme activity
Influences K+ levels
pH decrease (more acidic) depresses the central nervous system
Can lead to loss of consciousness
pH increase (more basic) can cause over-excitability
Tingling sensations, nervousness, muscle twitches
9. ■pH increases or decreases can alter the shape of the
enzyme rendering it non-functional
pH – Influences on enzyme activity
■Changes in enzyme structure can result in accelerated
or depressed metabolic actions within the cell
10. Addition of various acids or
alkalies by metabolic activities
alters body/blood pH.
pH – Why blood pH is Altered
11. Most Effective Buffer
By the law of mass action, at equilibrium
Henderson-Hasselbalch Equation
HA +
H+ A-
[H+] = K [HA]/[A-]
pH = log 1/ [H+]
Log 1/[H+] = log 1/K +log [A-]/[HA] pH = pK + log [A-]/[HA]
Thus pH= pK
Thus most effective buffers in the body are those with pK close to the pH
in which they operate.
This equation reflects that buffering capacity of buffer system is greatest
when amount of anion[A-] and undissociated acid [HA] is same.
K = [H+][A-] / [HA] K = Dissociation constant of acid
12. Acid Base balance is a homeostatic mechanism
Acid Base Balance is a physiological
and biochemical mechanism
associated to maintain body/blood pH.
Acid Base Balance
Carried out to regulate the altered pH of blood
and other body compartments to its normal
constant range.
Maintenance of Acid Base balance is a prime
requisite to maintain normal healthy and active life
13. 13
First Line of Defense
Chemical Buffer System
Second Line of Defense
Respiratory Mechanism
Third Line of Defense
Renal Mechanism
Factors Regulating Acid Base Balance
React very rapidly (less than a second)
Reacts rapidly (seconds to minutes)
Reacts slowly (minutes to hours)
14. Depend on absolute concentration of salt & acid.
Chemical Buffer
Buffers mixture of weak acids and its salt with a strong base
Resist change in pH of blood when small amount of
acids or alkalis added to the medium.
Most effective within 1 pH unit of the pK of the buffer
15. Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3)
Maintain a 20:1 ratio : HCO3
- : H2CO3
HCl + NaHCO3 ↔ H2CO3 + NaCl
NaOH + H2CO3 ↔ NaHCO3 + H2O
Chemical Buffer – Bicarbonate Buffer
Weak acid H2CO3 formed during buffering action of Bicarbonate buffer is then expired out by Lungs.
Thus Bicarbonate buffer is connected to the respiratory system
Bicarbonate buffer is also termed as Respiratory buffer.
Alkali reserve is represented by the concentration of NaHCO3 in the
blood.
Alkali reserve concentration(HCO3-) determines the strength of buffering action towards
added H+ ions by acids.
More the concentration of Alkali reserve ,more is the buffering action and vice a versa.
16. ■ This system is most important because the concentration
of both components can be regulated:
Loss of HCl
Addition of lactic acid
Exercise
Vomiting
CO2 + H2O H2CO3
Chemical Buffer – Bicarbonate Buffer
■ Carbonic acid by the respiratory system
■ Bicarbonate by the renal system
17. REMEMBER…….
Buffer cannot remove H+ ions from the body temporarily reduce free
H+ ions
Chemical Buffer – Bicarbonate Buffer
Buffers act quickly but not permanently
H+ ions have to be ultimately removed by the renal mechanism.
The blood buffers are effective as long as The acid load added is not
very high and the alkali reserve (HCO3 -) is not exhausted.
18. Na2
HPO4+ H+ NaH2
PO4+ Na+
Chemical Buffer – Phosphate Buffer
■ Most important in the intracellular system
19. Chemical Buffer – Protein Buffer
■ The most abundant buffer of the body.
■ Behaves as a buffer in both plasma and cells
■ Hemoglobin is by far the most important protein buffer.
■ Most important intracellular buffer.
O
H-
O
H-
O
H-
H
+
H
+
O
+
H-
H
+
H
+
H
+
H
+
O
H-
O
H-
H
+
O
H-
O
H+-
H+
O
H-
H
+
O
H-
H+
H
+
H
+
H+O
H-
H
+
H
+
H
+
H
+
H
+
20. ■ Bound H+to Hb (Hemoglobin) does not contribute to the acidity of blood.
Hb
O
2
O
2
O
2
O
2
■ Liberated H+from H2O combines with HCO3
-
HCO3
- H2CO3 CO2(exhaled)
Chemical Buffer – Protein Buffer
■ H+generated at the tissue level from the dissociation of H2CO3produced
by the addition of CO2.
■ As H+Hb picks up O2from the lungs the Hb which has a higher affinity
for O2releases H+and picks up O2
■ The Imidazole group of Histidine present in Hb structure has
buffering capacity
21. CO2 +H2O H2CO3 H+ + HCO3
Respiratory Regulation
■ Hyperventilation in response to increased CO2 or H+(low pH)
■ Hypoventilation in response to decreased CO2or H+(high pH)
■ Respiratory center in brain is able to detect blood concentration levels of CO2
and H+
■ Increases in CO2 and H+stimulate the respiratory center ↑ RR
■ But the effect diminishes in 1 -2 minutes
■ Respiratory regulation is by increasing or decreasing the exhalation of CO2
from the body.
22. Role of respiration in acid base balance is short term regulatory
process.
VOLATILE ACIDS
Doesn’t affect fixed
acids like lactic acid.
Role of Respiratory Regulation
Respiratory system plays second line of defense mechanism of
Acid Base Balance
24. H2CO3 formed from Bicarbonate Buffer, is exhaled
out through respiratory system.
Increased H2CO3 stimulates the respiratory centre in
Medulla Oblongata.
This in turn stimulates hyperventilation which
promptly removes H2CO3 from blood by expiration.
H+ + HCO3
- ↔ H2CO3 ↔ CO2 + H20
Role of Respiratory Regulation
25. Low H2CO3 concentration
Depresses respiratory center
Hypoventilation
Slow and shallow respiration.
Retains H2CO3 in blood
Role of Respiratory Regulation
26. Blood pH can be
adjusted through
respiratory
mechanism. By
changing rate and
depth of breathing.
If Nervous centre /
Respiratory system
fails.
Acid Base Balance
fails.
Role of Respiratory Regulation
27. Renal mechanism is the third line of
defense mechanism.
Renal Mechanism
Role of renal mechanism is long term
regulatory process.
28. Renal System maintains Acid Base Balance through:
Renal Mechanism
Excretion of Ammonium ions
(Glutaminase activity)
Reabsorption of Bicarbonate (HCO3-) ions.
Excretion of H ions
Excretion of titrable acids(Acid Phosphates)
29. Renal Mechanism
■ Secreted H+ is buffered with :
■ Secretion of H+ occurs in all segments of nephron
■ HCO3
-in proximal segments resulting in absorption of HCO3-
■ Na2
HPO4& NH3in distal segments in production of new HCO3-
31. 31
Excretion Of H+ ions
~Elimination of nonvolatile acid
~Excretion of H+
~Occurs in PCT
~Regeneration of bicarbonate
~H+ combine with non carbonate base and excreated
32. ~Measure of acid excreated by kidney
~Role of phosphate buffer
Reclamation of bicarbonate.
33. 33
EXCRETION OF AMMONIUM ION
NH3 is obtained from Deamination of Glutamine
NH4
+ cant diffuse back
2/3 of body acid load liberated in the form of NH4
+
34.
35.
36. MECHANISM FOR REGULATION OF
ACID BASE BALANCE
Buffer system: temporary solution
Respiratory mechanism provide short time regulation
Renal mechanism : permanent solution
Urine pH < plasma pH ,4.5-9.5
Eliminate nonvolatile acid, buffered by cation (principally
Na+)
Maintain alkali reserve