This document discusses acid-base balance in the human body. It explains that pH is tightly regulated through carbon dioxide tension, plasma bicarbonate levels, and renal mechanisms. The lungs, kidneys, and cells all work to maintain homeostasis. When acid-base balance is disturbed, the condition can be either respiratory or metabolic in nature. The document outlines the various buffer systems, including bicarbonate, phosphate and proteins. It also explains how the lungs and kidneys work to compensate for respiratory and metabolic acid-base disturbances respectively.

1. Acid -Base balance
Dr mugarura Robert

2. Human Acid-base Homeostasis
• Tight regulation:
• CO2 tension
• by respiratory excretion (of volatile acids)
• Plasma bicarbonate [HCO3
-]
• By renal HCO3
- reabsorption and
• Elimination of protons produced by metabolism
• pH is determined by CO2 tension and [HCO3
-]

3. Acid base balance
• Normal ranges PH 7.35 to 7.45
• Alkalosis PH > 7.45
• Acidosis PH < 7.35
• Disorders of acid base balance can be :
• Respiratory
• Metabolic

4. Body acids
• Fixed acids
• SO4, PO4 , lactic acid, fatty acids, ketone bodies,
• Are products of metabolism- 1 mmol of fixed acid/kg body weight per day (60 kg=60 mmol/day)
• Volatile: H2CO3
• Product of respiration- external

5. Acidosis
• Increased PCO2
• Increased A tot- (hyperphosphatemia, hyperproteinemia)

6. Alkalosis
• Decreased PCO2
• decreased A tot- (hypophosphatemia, hypoproteinemia

7. Normal Values
• [HCO3
-] ~ 24 mM
• PaCO2 = 38 torr
• pH ~ 7.42
• Plasma HCO3
- regulation by
• reclaiming filtered HCO3
- and
• generating new HCO3
- (carboanhydrase)
• ( to replace the lost internally titrating metabolic acid and
externally from the GI tract)
• Production of 1 mmol of acid/kg body weight per
day (60 kg=60 mmol/day)

8. ..
For optimal functioning of cells Acids and bases in the body must be in balance.

9. Body pH Balance
• Chemical blood buffers:
• Physiological Buffer Systems
• Lungs,
• Cells,
• Kidneys

10. Chemical Buffer Systems
• Chemical buffer: system of one or more compounds that act to
resist pH changes when strong acid or base is added
1. Bicarbonate buffer system
2. Phosphate buffer system
3. Protein buffer system

11. Bicarbonate Buffer System
• Mixture of H2CO3 (weak acid) and salts of HCO3
– (e.g., NaHCO3, a
weak base)
• Buffers ICF and ECF
• The only important ECF buffer

12. Bicarbonate Buffer System
• If strong acid is added:
• HCO3
– ties up H+ and forms H2CO3
• HCl + NaHCO3  H2CO3 + NaCl
• pH decreases only slightly, unless all available HCO3
– (alkaline reserve) is used
up
• HCO3
– concentration is closely regulated by the kidneys

13. Bicarbonate Buffer System
• If strong base is added
• It causes H2CO3 to dissociate and donate H+
• H+ ties up the base (e.g. OH–)
• NaOH + H2CO3  NaHCO3 + H2O
• pH rises only slightly
• H2CO3 supply is almost limitless (from CO2 released by respiration) and is
subject to respiratory controls

14. Phosphate Buffer System
• Action is nearly identical to the bicarbonate buffer
• Components are sodium salts of:
• Dihydrogen phosphate (H2PO4
–), a weak acid
• Monohydrogen phosphate (HPO4
2–), a weak base
• Effective buffer in urine and ICF, where phosphate concentrations are
high

15. Protein Buffer System
• Intracellular proteins are the most plentiful and powerful buffers;
plasma proteins are also important
• Protein molecules are amphoteric (can function as both a weak acid
and a weak base)
• When pH rises, organic acid or carboxyl (COOH) groups release H+
• When pH falls, NH2 groups bind H+

16. Physiological Buffer Systems
• Respiratory and renal systems
• Act more slowly than chemical buffer systems
• Have more capacity than chemical buffer systems

17. Respiratory Regulation of H+
• Respiratory system eliminates CO2
• A reversible equilibrium exists in the blood:
• CO2 + H2O  H2CO3  H+ + HCO3
–
• During CO2 unloading the reaction shifts to the left (and H+ is
incorporated into H2O)
• During CO2 loading the reaction shifts to the right (and H+ is buffered
by proteins)

18. Total Acid- base Metabolism
Henderson-Hasselbalch 1909,1916
HCO3
-
• pH = pK + log ------------
PaCO2
Result of Metabolic
and Respiratory
Interplay
Primary
Respiratory
Disorders Altered by Respiratory
Compensation for
Metabolic Disorders
Metabolic comp.
Respiratory
component
Altered by
Buffering
Primarily Altered
in Metabolic Disorders

19. Respiratory Regulation of H+
• Hypercapnia activates medullary chemoreceptors
• Rising plasma H+ activates peripheral chemoreceptors
• More CO2 is removed from the blood
• H+ concentration is reduced

20. Respiratory Regulation of H+
• Alkalosis depresses the respiratory center
• Respiratory rate and depth decrease
• H+ concentration increases
• Respiratory system impairment causes acid-base imbalances
• Hypoventilation  respiratory acidosis
• Hyperventilation  respiratory alkalosis

21. Acid-Base Balance
• Chemical buffers cannot eliminate excess acids or bases from the
body
• Lungs eliminate volatile carbonic acid by eliminating CO2
• Kidneys eliminate other fixed metabolic acids (phosphoric, uric, and lactic
acids and ketones) and prevent metabolic acidosis

22. Renal Mechanisms of Acid-Base Balance
• Most important renal mechanisms
• Conserving (reabsorbing) or generating new HCO3
–
• Excreting HCO3
–
• Generating or reabsorbing one HCO3
– is the same as losing one H+
• Excreting one HCO3
– is the same as gaining one H+

23. Renal Mechanisms of Acid-Base Balance
• Renal regulation of acid-base balance depends on secretion of H+
• H+ secretion occurs in the PCT and in collecting duct type A
intercalated cells:
• The H+ comes from H2CO3 produced in reactions catalyzed by carbonic
anhydrase inside the cells
• See Steps 1 and 2 of the following figure

24. Figure 26.12
1 CO2 combines with water
within the tubule cell,
forming H2CO3.
2 H2CO3 is quickly split,
forming H+ and bicarbonate
ion (HCO3
–).
3a H+ is secreted into the filtrate.
3b For each H+ secreted, a HCO3
– enters the
peritubular capillary blood either via symport
with Na+ or via antiport with CI–.
4 Secreted H+ combines with HCO3
– in the
filtrate, forming carbonic acid (H2CO3). HCO3
–
disappears from the filtrate at the same rate
that HCO3
– (formed within the tubule cell)
enters the peritubular capillary blood.
5 The H2CO3
formed in the
filtrate dissociates
to release CO2
and H2O.
6 CO2 diffuses
into the tubule
cell, where it
triggers further H+
secretion.
* CA
CO2
CO2
+
H2O
2K+2K+
*
Na+ Na+
3Na+3Na+
Tight junction
H2CO3
H2CO3
PCT cell
NucleusFiltrate in
tubule lumen
Cl–Cl–HCO3
– + Na+
HCO3
–
H2O CO2
H+ H+ HCO3
–
HCO3
–
HCO3
–
ATPase
ATPase
Peri-
tubular
capillary
1
2
4
5
6
3a 3b
Primary active
transport
Simple diffusion
Secondary active
transport
Carbonic anhydrase
Transport protein

25. Reabsorption of Bicarbonate
• Tubule cell luminal membranes are impermeable to HCO3
–
• CO2 combines with water in PCT cells, forming H2CO3
• H2CO3 dissociates
• H+ is secreted, and HCO3
– is reabsorbed into capillary blood
• Secreted H+ unites with HCO3
– to form H2CO3 in filtrate, which generates CO2
and H2O
• HCO3
– disappears from filtrate at the same rate that it enters the
peritubular capillary blood

26. Figure 26.12
1 CO2 combines with water
within the tubule cell,
forming H2CO3.
2 H2CO3 is quickly split,
forming H+ and bicarbonate
ion (HCO3
–).
3a H+ is secreted into the filtrate.
3b For each H+ secreted, a HCO3
– enters the
peritubular capillary blood either via symport
with Na+ or via antiport with CI–.
4 Secreted H+ combines with HCO3
– in the
filtrate, forming carbonic acid (H2CO3). HCO3
–
disappears from the filtrate at the same rate
that HCO3
– (formed within the tubule cell)
enters the peritubular capillary blood.
5 The H2CO3
formed in the
filtrate dissociates
to release CO2
and H2O.
6 CO2 diffuses
into the tubule
cell, where it
triggers further H+
secretion.
* CA
CO2
CO2
+
H2O
2K+2K+
*
Na+ Na+
3Na+3Na+
Tight junction
H2CO3
H2CO3
PCT cell
NucleusFiltrate in
tubule lumen
Cl–Cl–HCO3
– + Na+
HCO3
–
H2O CO2
H+ H+ HCO3
–
HCO3
–
HCO3
–
ATPase
ATPase
Peri-
tubular
capillary
1
2
4
5
6
3a 3b
Primary active
transport
Simple diffusion
Secondary active
transport
Carbonic anhydrase
Transport protein

27. Generating New Bicarbonate Ions
• Two mechanisms in PCT and type A intercalated cells
• Generate new HCO3
– to be added to the alkaline reserve
• Both involve renal excretion of acid (via secretion and excretion of H+
or NH4
+

28. Excretion of Buffered H+
• Dietary H+ must be balanced by generating new HCO3
–
• Most filtered HCO3
– is used up before filtrate reaches the collecting
duct

29. Excretion of Buffered H+
• Intercalated cells actively secrete H+ into urine, which is buffered by
phosphates and excreted
• Generated “new” HCO3
– moves into the interstitial space via a
cotransport system and then moves passively into peritubular
capillary blood

30. Figure 25.13
Active
transport
Passive
transport
Peri-
tubular
capillary
2
4
4
3
31
1 2 43
Filtrate
in tubule
lumen
Transcellular
Paracellular
Paracellular
Tight junction Lateral intercellular space
Capillary
endothelial
cell
Luminal
membrane
Solutes
H2O
Tubule cell Interstitial
fluid
Transcellular
Basolateral
membranes
1 Transport across the
luminal membrane.
2 Diffusion through the
cytosol.
4 Movement through the interstitial
fluid and into the capillary.
3 Transport across the basolateral
membrane. (Often involves the lateral
intercellular spaces because
membrane transporters transport ions
into these spaces.)
Movement via the
transcellular route
involves:
The paracellular route
involves:
• Movement through
leaky tight junctions,
particularly in the PCT.

31. Ammonium Ion Excretion
• Involves metabolism of glutamine in PCT cells
• Each glutamine produces 2 NH4
+ and 2 “new” HCO3
–
• HCO3
– moves to the blood and NH4
+ is excreted in urine

32. Figure 26.14
Nucleus
PCT tubule cells
Filtrate in
tubule lumen
Peri-
tubular
capillary
NH4
+
out in urine
2NH4
+
Na+
Na+ Na+ Na+ Na+
3Na+
3Na+
Glutamine GlutamineGlutamine
Tight junction
Deamination,
oxidation, and
acidification
(+H+)
2K+2K+
NH4
+ HCO3
–
2HCO3
– HCO3
–
(new)
ATPase
1 PCT cells metabolize glutamine to
NH4
+ and HCO3
–.
2a This weak acid NH4
+ (ammonium) is
secreted into the filtrate, taking the
place of H+ on a Na+- H+ antiport carrier.
2b For each NH4
+ secreted, a
bicarbonate ion (HCO3
–) enters the
peritubular capillary blood via a
symport carrier.
3 The NH4
+ is excreted in the urine.
Primary
active
transport
Simple
diffusion
Secondary
active
transport
Transport
protein
1
2a 2b
3

33. Bicarbonate Ion Secretion
• When the body is in alkalosis, type B intercalated cells
• Secrete HCO3
–
• Reclaim H+ and acidify the blood

34. Bicarbonate Ion Secretion
• Mechanism is the opposite of the bicarbonate ion reabsorption
process by type A intercalated cells
• Even during alkalosis, the nephrons and collecting ducts excrete fewer
HCO3
– than they conserve

35. Abnormalities of Acid-Base Balance
• Respiratory acidosis and alkalosis
• Metabolic acidosis and alkalosis

36. Respiratory Acidosis and Alkalosis
• The most important indicator of adequacy of respiratory function is
PCO2
level (normally 35–45 mm Hg)
• PCO2
above 45 mm Hg  respiratory acidosis
• Most common cause of acid-base imbalances
• Due to decrease in ventilation or gas exchange
• Characterized by falling blood pH and rising PCO2

37. Respiratory Acidosis and Alkalosis
• PCO2
below 35 mm Hg  respiratory alkalosis
• A common result of hyperventilation due to stress or pain

38. Metabolic Acidosis and Alkalosis
• Any pH imbalance not caused by abnormal blood CO2 levels
• Indicated by abnormal HCO3
– levels

39. Metabolic Acidosis and Alkalosis
• Causes of metabolic acidosis
• Ingestion of too much alcohol ( acetic acid)
• Excessive loss of HCO3
– (e.g., persistent diarrhea)
• Accumulation of lactic acid, shock, ketosis in diabetic crisis, starvation, and
kidney failure

40. Metabolic Acidosis and Alkalosis
• Metabolic alkalosis is much less common than metabolic acidosis
• Indicated by rising blood pH and HCO3
–
• Caused by vomiting of the acid contents of the stomach or by intake of excess
base (e.g., antacids)

41. Effects of Acidosis and Alkalosis
• Blood pH below 7  depression of CNS  coma  death
• Blood pH above 7.8  excitation of nervous system  muscle
tetany, extreme nervousness, convulsions, respiratory arrest

42. Respiratory and Renal Compensations
• If acid-base imbalance is due to malfunction of a physiological buffer
system, the other one compensates
• Respiratory system attempts to correct metabolic acid-base imbalances
• Kidneys attempt to correct respiratory acid-base imbalances

43. Respiratory Compensation
• In metabolic acidosis
• High H+ levels stimulate the respiratory centers
• Rate and depth of breathing are elevated
• Blood pH is below 7.35 and HCO3
– level is low
• As CO2 is eliminated by the respiratory system, PCO2
falls below normal

44. Respiratory Compensation
• Respiratory compensation for metabolic alkalosis is revealed by:
• Slow, shallow breathing, allowing CO2 accumulation in the blood
• High pH (over 7.45) and elevated HCO3
– levels

45. Renal Compensation
• Hypoventilation causes elevated PCO2
• (respiratory acidosis)
• Renal compensation is indicated by high HCO3
– levels
• Respiratory alkalosis exhibits low PCO2
and high pH
• Renal compensation is indicated by decreasing HCO3
– levels

46. Developmental Aspects
• Infants have proportionately more ECF than adults until about 2 years of
age
• Problems with fluid, electrolyte, and acid-base balance are most common
in infancy, reflecting
• Low residual lung volume
• High rate of fluid intake and output
• High metabolic rate, yielding more metabolic wastes
• High rate of insensible water loss
• Inefficiency of kidneys, especially during the first month

47. Developmental Aspects
• At puberty, sexual differences in body water content arise as males
develop greater muscle mass
• In old age, total body water often decreases
• Homeostatic mechanisms slow down with age
• Elders may be unresponsive to thirst clues and are at risk of
dehydration