Physiology of Acid-Base Balance: Homeostasis by Kidneys & Disorders 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
- secretion
8.Disorders a Acid-Base Balance
Counter-Current Mechanism | © Prof. Dr. Rashid Mahmood1 May 2018 4

5. Acid Base Balance
• For normal body functions and normal enzymes activities, a normal
hydrogen ion conc. i.e. normal pH is essential.
• pH is the negative log of H+ conc.
• Normal [H+] of arterial blood = 0.00004 mEq/lit (40 nEq/L) which is
equal to pH of 7.4
• pH of venous blood = 7.35
• Intracellular pH is slightly lower than PLASMA pH
• pH of urine = 4.5 – 8
• A pH of body fluids less than normal = Acidosis
• A pH of body fluids more than normal = Alkalosis
Acid Base Balance | © Prof. Dr. Rashid Mahmood

6. 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

7. 1. Buffer Systems of Body Fluids:
•Buffer: Any substance that can reversibly
bind H+
•Buffer solution: resists change in pH
Acid Base Balance | © Prof. Dr. Rashid Mahmood

8. Buffer systems
• Buffer system reacts with in fraction of
second
• Only keep H+ tied up
Acid Base Balance | © Prof. Dr. Rashid Mahmood

9. i. HCO3
- Buffer System: consist of
H2CO3 / NaHCO3
•Quantitatively most important buffer
system of extracellular fluid
•PK = 6.1
Acid Base Balance | © Prof. Dr. Rashid Mahmood

10. ii. Phosphate Buffer System:
Na2HPO4 + NaH2PO4
• Important buffer system in renal tubular fluid and I.C.F
• PK – 6.8
• Especially important for renal tubular fluid because
1. Phosphates are concentrated
2. pH of tubular fluid is lower than pH of E.C.F i.e. it is close to PK
of system
Acid Base Balance | © Prof. Dr. Rashid Mahmood

11. iii. Proteins: important
intracellular buffer system
• Higher concentration with in the cells
•PK close to 7.4
Acid Base Balance | © Prof. Dr. Rashid Mahmood

12. 2. Respiratory Regulation:
• 2nd line of defense
• Acts with in a few minutes (3 – 12 min)
• Controls pH by altering CO2 elimination form body by lungs
H+ + HCO3  H2CO3  CO2 + H2O
Acid Base Balance | © Prof. Dr. Rashid Mahmood

13. 3. Renal Control of Acid Base
Balance:
•By excreting an acidic or basic
urine
•Relatively slow to response
•Most powerful Acid Base
regulatory system
Acid Base Balance | © Prof. Dr. Rashid Mahmood

14. Mechanism:
•80 mEq of non-volatile
acids
•4320 mEq HCO3- / day
•Each HCO3
- reabsorption requires a H+
secretion
•So 4320 + 80 = 4400 mEq of H+/dayAcid Base Balance | © Prof. Dr. Rashid Mahmood

15. 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

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

17. Mechanism of H+
secretion is different
in different tubular
segments.
Acid Base Balance | © Prof. Dr. Rashid Mahmood

18. H+ secretion in early tubular segment
(up to early DCT)
•Na K ATPase
pump
•Na H counter
transport
Acid Base Balance | © Prof. Dr. Rashid Mahmood

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

20. Combination of excess H + with urinary
buffers and generation of new HCO3
- ions:
• H+ secreted 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

21. Phosphate buffer system: (HPO4 / H2PO4)
• 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
Acid Base Balance | © Prof. Dr. Rashid Mahmood

22. 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

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

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

25. 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

26. Metabolic Acidosis:
• Any type of acidosis except those caused by excessive
CO2.
• Causes
1. Failure of kidney to excrete metabolic acids normally formed in
the body.
2. Formation of excessive quantity of metabolic acids in the body
e.g. Diabetes Mellitus
3. Ingestion of acids e.g. Aspirin, Methyl alcohol.
4. Loss of base e.g. failure of kidneys to reabsorb HCO3
-Severe,
diarrhea, and vomiting of intestinal contents, large quantity of
HCO3
-are lostAcid Base Balance | © Prof. Dr. Rashid Mahmood

27. 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

28. Respiratory Compensation of Metabolic
Acidosis
•Acidosis 
stimulation of respiratory center 
 rate of depth of respiratory 
fall in CO2
Acid Base Balance | © Prof. Dr. Rashid Mahmood

29. Renal Compensation of Metabolic Acidosis
•C. Renal compensation (hours to
days)
• secretion of H+ in tubular human have
two effects
•Complete reabsorption of HCO3
-
• loss H+ in combination with urinary
buffers e.g. HPO4 / H2PH4, NH3 etc.
Acid Base Balance | © Prof. Dr. Rashid Mahmood
Contd…..

30. Renal Compensation of Metabolic Acidosis
•As there are  HCO3
- in plasma, so 
filtration of HCO3
-, so less utilization of H+
to neutralize HCO3
- which further  H+ loss
in urine
• regeneration of new HCO3
- ions by
•Phosphate buffer system
•NH3 buffer system
•Glutamine metabolism
• H+ stimulate glutamineAcid Base Balance | © Prof. Dr. Rashid Mahmood
Contd…..

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

32. Causes:
1. Vomiting of gastric contents or suction through
Naso-gastric tube
2. Administration of diuretics – chlorthiazide
3. Excessive aldosterone secretion
4. Hypokalemia:- Which lead to greater loss of H+
5. Ingestion of alkaline drugs e.g. sod bicarbonate
Acid Base Balance | © Prof. Dr. Rashid Mahmood

33. 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 significanceAcid Base Balance | © Prof. Dr. Rashid Mahmood
Contd…..

34. 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…..

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

36. Respiratory Alkalosis
•Compensation
•Chemical buffers
•Renal compensation
• filtration of HCO3
-, but as there are less
H+ secretion, so less HCO3
- reabsorption
• HCO3
- regeneration.
•in chronic cases:-  secretion of HCO3
-
Acid Base Balance | © Prof. Dr. Rashid Mahmood

37. Analysis of simple acid-base disorders

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

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

40. 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 editionVascular
distensibility &
Functions of
Arterial and
Venous System |
401-May-18

41. Take Home Points (1/3)
1-May-18 41
•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

42. Take Home Points (2/3)
1-May-18 42
•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

43. •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)

44. Thank You
Acid Base Balance | © Prof. Dr. Rashid Mahmood
Questions ?
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rashid.mahmood@rmi.edu.pk
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