Physiology of Acid base balance

1. Acid Base Balance
Prof. Dr. Rashid Mahmood

2. Acid Base Balance
(Review)
Prof. Dr. Rashid Mahmood

3. Objectives
♦Identify the defense mechanisms the body uses to minimize the impact
of acid and alkali on the pH of body fluids
♦Distinguish among the roles of the kidneys, lungs, and liver in acid-base
balance
♦Describe the mechanisms for H+ transport in the various segments of
the nephron and ways that these mechanisms are regulated
♦Distinguish between the reabsorption of the filtered load of HCO3− and
the generation of new HCO3−
♦Explain the importance of urine buffers, and especially NH4+
production and excretion, in the process of new HCO3
− formation
♦Distinguish between metabolic and respiratory acid-base disorders
Acid Base Balance | © Prof. Dr. Rashid Mahmood

4. Lesson Contents
1. Defenses against change in [H+]
2.Buffer system of the body
3.Respiratory Regulation of Acid-Base Balance
4.Renal Control of Acid-Base Balance
5.H+ secretion in different parts of nephron
6.HCO3
- Reabsorption in different parts of
nephron
7.New HCO3
- generation
8.Disorders of Acid-Base Balance
Counter-Current Mechanism | © Prof. Dr. Rashid Mahmood
16 July 2021 4

5. Defenses against change in [H+]
•Buffer system of body fluids
•Respiratory regulation of acid – base balance
•Renal control of acid base balance
Acid Base Balance | © Prof. Dr. Rashid Mahmood

6. Preamble
•Q. 1-3: Pretest;
•Q. 4-6: Post-test
Acid Base Balance | © Prof. Dr. Rashid Mahmood

7. Defenses against change in [H+]
Acid Base Balance | © Prof. Dr. Rashid Mahmood
System Rapidity Sequence of
action
Action
Buffer
systems
with in
fraction of
second
1st line of
action
Only keep H+
tied up
Respiratory
System
few minutes
(3 – 12 min)
2nd line of
action
altering CO2
elimination
Renal Control Relatively
slow (Most
powerful)
3rd line of
action
excreting an
acidic or basic
urine

8. Buffer systems
Buffer System Components Main site of action
HCO3
- Buffer
System
H2CO3 / NaHCO3 extracellular fluid
Phosphate Buffer
System
Na2HPO4 +,
NaH2PO4
renal tubular fluid
(and I.C.F)
Proteins in the cells
Acid Base Balance | © Prof. Dr. Rashid Mahmood

9. Kidneys regulate pH by three basic
mechanisms
•Secretion of H+
•Reabsorption of filtered
HCO3
-
•Production of new HCO3
-
Acid Base Balance | © Prof. Dr. Rashid Mahmood

10. Mechanism of H+
secretion is different
in different tubular
segments.
Acid Base Balance | © Prof. Dr. Rashid Mahmood
Associated with HCO3- - Reabsorption in
Early segments of Nephron

11. H+ secretion in early tubular segment
(PCT, Thick AL, DCT)
•Na K ATPase
pump
•Na H counter
transport
Acid Base Balance | © Prof. Dr. Rashid Mahmood

12. H+ secretion in late tubular segments (Late
DCT; intercalated cells)
 Hydrogen
ATPase
H+- K+ ATPase
Acid Base Balance | © Prof. Dr. Rashid Mahmood

13. Reabsorption of HCO3
-
Acid Base Balance | © Prof. Dr. Rashid Mahmood

14. Generation of new HCO3
- ions and Combination
of excess H + with urinary buffers:
• H+ secreted in excess of HCO3
- filtered
are excreted in free ionic form or in
combination with urinary buffers.
• Two buffer systems in renal tubules:
1. Phosphate buffer system: (HPO4 /
H2PO4)
2. Ammonia buffer system
Acid Base Balance | © Prof. Dr. Rashid Mahmood

15. • HCO3
- is
reabsorbed in
interstitial fluid
and as this
HCO3
- ion has
not come from
tubular fluid,
so we say, that
a new HCO3
- is
added to the
blood for each
H+ secreted
1. Phosphate buffer system: (HPO4 / H2PO4)
and Generation of new HCO3- -

16. 2. Ammonia buffer system
and Generation of new HCO3
-
• Composed of NH3 and NH4
•Quantitatively more important than phosphate
buffer system
•Mechanism of H + secretion and new HCO3
-
regeneration is different in proximal tubules and
collecting tubules.
Acid Base Balance | © Prof. Dr. Rashid Mahmood

17. Proximal tubules and thick
ascending and distal tubules
Acid Base Balance | © Prof. Dr. Rashid Mahmood

18. Collecting ducts
Freely
Permeable
To NH3,
Not
Permeable
To NH4
+
Acid Base Balance | © Prof. Dr. Rashid Mahmood

19. How many legs?
Acid Base Balance | © Prof. Dr. Rashid Mahmood

20. Disorders of
acid base
balance
Acidosis
Respiratory
Acidosis
(↑ pCO2)
Respiratory
Alkalosis
(↓ pCO2)
Alkalosis
Metabolic
Acidosis
(all causes
Other than↑
pCO2)
Metabolic
Alkalosis
(all causes
Other than↓ pCO2)
Acid Base Balance | © Prof. Dr. Rashid Mahmood

21. Acid Base Balance | © Prof. Dr. Rashid Mahmood
Primary event is indicated by the double arrows
Arterial Blood

22. Metabolic Acidosis
•Any type of acidosis except
those caused by excessive
CO2
Acid Base Balance | © Prof. Dr. Rashid Mahmood

23. Compensation of Metabolic Acidosis
A. Chemical Buffers (immediately)
B. Respiratory compensation (in
minutes)
C. Renal compensation (hours to
days)
Acid Base Balance | © Prof. Dr. Rashid Mahmood

24. Respiratory Compensation of Metabolic
Acidosis
•Acidosis 
stimulation of respiratory center
Acid Base Balance | © Prof. Dr. Rashid Mahmood

25. Renal Compensation of Metabolic Acidosis
(hours to days)
•4 mechanisms:
1. Complete reabsorption of HCO3
-
2.  loss H+ in combination with urinary
buffers e.g. HPO4 / H2PH4, NH3 etc.
3.  filtration of HCO3
- →  utilization of H+
to neutralize HCO3
-
4.  regeneration of new HCO3- ions ( H+
stimulates glutamine)
Acid Base Balance | © Prof. Dr. Rashid Mahmood
Contd…..

26. Metabolic Alkalosis
•pH of blood 
• HCO3
-
• loss of H+
Acid Base Balance | © Prof. Dr. Rashid Mahmood

27. Compensation of Metabolic Alkalosis
•Usually not much helpful and is very
difficult
a. Chemical buffers
b. Respiratory compensation
• ventilation   respiratory rate   PCO2
  H2CO3
•But soon  PCO2 stimulate respiration
•So compensation is not of great significance
Acid Base Balance | © Prof. Dr. Rashid Mahmood
Contd…..

28. Compensation of Metabolic Alkalosis
•c. Renal compensation:
• HCO3
- secretion in renal tubules
• reabsorption of filtered HCO3
-
• new synthesis of HCO3
-
Acid Base Balance | © Prof. Dr. Rashid Mahmood
Contd…..

29. Compensation of Respiratory
Acidosis
•Chemical Buffers
•Renal compensation
• secretion of H+
• reabsorption of HCO3-
• regeneration of HCO3-
Acid Base Balance | © Prof. Dr. Rashid Mahmood

30. Compensation of Respiratory Alkalosis
•Chemical buffers
•Renal compensation
• HCO3
- reabsorption
• HCO3
- regeneration
•in chronic cases:-  secretion of HCO3
-
Acid Base Balance | © Prof. Dr. Rashid Mahmood

31. Analysis of simple acid-base disorders


32. Home Task/ Self-Study
•Effects of Acid-Base disorders on Na+, K+
and Ca++ concentration
•Causes & Treatment of Acid-Base disorders
•Anion gap
•Titrable acid
Acid Base Balance | © Prof. Dr. Rashid Mahmood

33. Learning Resources
•Guyton and Hall (Text book of physiology),
13th Edition
•Berne & Levy Principles of Physiology
(Koeppen BM), 6th Edition
•Human Physiology, Silverthorn
•Human Physiology : from cells to system,
Lauralee Sherwood, 9th edition
Vascular
distensibility &
Functions of
Arterial and
Venous System |
33
16-Jul-21

34. Take Home Points (1/3)
16-Jul-21 34
•Homeostasis of pH of body fluids is
maintained by three main mechanisms:
•1st line of defense is Buffer Systems of body
fluids that react immediately but only keep H+
tied up
•2nd line of defense is respiratory regulation
that acts in a few minutes
•3rd line of defense is renal control of Acid-
Base Balance that is relatively slow to respond

35. Take Home Points (2/3)
16-Jul-21 35
•Kidneys regulate pH by three basic mechanisms:
•Secretion of H+
•Reabsorption of filtered HCO3
-
•Production of new HCO3
-
• H+ secretion of early tubular segments occurs by
secondary active transport while in late tubule
segments it is by primary active transport
• Excess H+ in renal tubules combines with urinary
buffers that also generate new HCO3-
• There are two buffer systems in renal tubules:
•Phosphate buffer system & Ammonia Buffer system

36. •Metabolic acidosis refers to all types of acidosis
besides those caused by excess CO2
•Metabolic alkalosis results from increased
extracellular fluid HCO3
- concentration
•Respiratory acidosis results from increased PCO2
and decreased ventilation
•Respiratory alkalosis is caused by excessive
ventilation by the lungs
•Kidneys correct pH disorders by altering excretion
of H+ and addition of HCO3
- to the extra cellular
fluid Acid Base Balance | © Prof. Dr. Rashid Mahmood
Take Home Points (3/3)

37. Q. 4-6: Post-test
• Re-answer Q1-3, with explanation
Acid Base Balance | © Prof. Dr. Rashid Mahmood

38. Case
• A 22-year-old man with insulin-dependent diabetes mellitus is seen
in the emergency department. He reports that he “has had the flu
for the past couple days.” Because he has not felt well and was not
eating, he has not taken any insulin during the previous 24 hours. He
also reports taking two aspirin tablets before coming to the
emergency department because of a headache. On examination, he
is found to have rapid and deep respirations. The following
laboratory data are obtained:
pH 7.32 (normal: 7.40)
PO2 100 mm Hg (normal: 100 mm Hg)
PCO2 30 mm Hg (normal: 40 mm Hg)
[HCO3
−] 15 mEq/L (normal: 24 mEq/L)

39. 4. What type of acid-base disorder does this man have?
A. Metabolic acidosis
B. Metabolic alkalosis
C. Respiratory acidosis
D. Respiratory alkalosis
E. Mixed disorder (metabolic acidosis and respiratory alkalosis)
Acid Base Balance | © Prof. Dr. Rashid Mahmood
A
is correct because this is a case of diabetic ketoacidosis due to the lack of insulin.
The blood gas analysis shows that he has a metabolic acidosis with appropriate
respiratory compensation, which is secondary to the generation and accumulation
of keto acids that occurs when insulin levels are not adequate.

40. 5. Why are this man’s respirations rapid and deep?
A. The decrease in Pco2 has stimulated his respiratory center.
B. Hypoxemia has stimulated his respiratory center.
C. This is the normal respiratory response to his acid-base
disturbance.
D. There is poor pulmonary gas exchange caused by an infection in
his lungs.
E. Aspirin has stimulated his respiratory center.
Acid Base Balance | © Prof. Dr. Rashid Mahmood
C
is correct because the normal respiratory response to a metabolic acidosis is to
increase the ventilation rate (i.e., rapid and deep breathing) to reduce the Pco2.
This respiratory compensation is mediated by the respiratory center’s response to
the acidosis.

41. 6. What is the most important component of the compensatory
response of this man’s kidneys to his acid-base disorder?
A. Increased filtered load of HCO3−
B. Decreased secretion of H+ by the proximal tubule
C. Increased production and excretion of NH4+
D. Decreased H+ secretion by the collecting duct
E. Increased secretion of HCO3− by the collecting duct
Acid Base Balance | © Prof. Dr. Rashid Mahmood
C
is correct because the renal compensatory response to a metabolic acidosis is to
increase the excretion of net acid. This occurs primarily through the production
and excretion of NH4+. Moreover, expression and activity of the proximal tubule
enzymes responsible for glutamine metabolism are increased by acidosis.

42. Thank You
Acid Base Balance | © Prof. Dr. Rashid Mahmood
Questions ?
Comments ?
drrashid62@gmail.com
rashid.mahmood@rmi.edu.pk
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