Acid-Base Homeostasis-First line, second line and third line of defense of pH of body fluid

1. ACID-BASE Homeostasis
David C. Ikwuka
Department of Human Physiology
| Nnamdi Azikiwe University Nnewi Campus, Nigeria
Lecture Slide

2. Presentation Overview
2
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 Homeostatic Acid-Base
Balance
 Blood pH Regulation
 Buffer Systems
/Mechanism
 Chemical Buffers
 Role of Kidney in Acid-
Base Homeostasis
 Acidification of Urine
 Regulation of H+ Secretion
 Closing Remarks &
Questions
4/30/2021
 Introduction
 Acids & Bases
 Dissociation of Water
 Concept of pH
 Acidity & Alkalinity in the
Body
 Effects of Fluctuations in
H+ Conc.
 Acid Production in the
Body

3. Introduction
 Acid-base homeostasis is concerned with the
regulation of free H+ conc. In the body fluids.
 Body is very sensitive to changes in pH &
powerful mechanisms are involved to tightly
regulate this balance maintaining it at a
narrow range.
 Outside this tolerable range, enzyme activity,
nerve and cardiac function are altered,
proteins are denatured and may ultimately
lead to death.
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4. Acids & Bases (Ions)
4
 An acid is any ionic
compound that
releases hydrogen _____
(H+) in solution.
 A base is any ionic
compound that
releases hydroxide
_____ (-OH) in solution.
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5. Dissociation of Water
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Neutral water has equal amounts of H+ and OH -
Acids: Excess of H+ in aqueous solution
Bases: Excess of OH- in aqueous solution
Acids & bases neutralize each other.
Ka

6. 6

7. 7

8. Concept of pH
 pH scale runs from 0 to 14 (concentration of H+ in
moles/liter)
 pH of 7 is neutral
(distilled water -- concentration of OH- and H+ are equal)
 pH below 7 is acidic ([H+] > [OH-]).
 pH above 7 is alkaline ([H+] < [OH-]).
 pH is a logarithmic scale
Example: a change of two or three pH units
pH of 1 contains 10x10=100 more H+ than pH of 3
pH of 8 contains 10x10x10=1000 more H+ than pH of 11
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9. Acidity of a solution >
measured by concentration
of hydrogen ions (H+).
pH ranges: 0 (very acidic) to 14 (very
alkaline).
Change in just one unit of scale
= tenfold change in H+
concentration.
If concentration of H+ = OH - …
neutral.
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10. pH Scale
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11. Acidosis & Alkalosis in the Body
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 pH of Arterial blood is 7.45 & Venous blood is
7.35 to give an average blood pH of 7.4.
 Acidosis exists when blood pH falls below
7.35 & Alkalosis occurs when blood pH is
>7.45. ie. The reference point for Acid-Base
Status is blood pH of 7.4 not chemically
neutral pH of 7.0
 If addition of acids exceeds excretion,
Acidosis results. Conversely, if excretion of
acids exceeds addition, Alkalosis results.
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12. Effects of Fluctuations in H+ Concentration
1. Changes Nerve & Muscle Excitability:
 ↑ed H+ (Acidosis)- Depression of synaptic transmission in
CNS (Patients become disoriented & may die of Coma)
 ↓ed H+ (Alkalosis)- Overexcitability of NS from PNS to
CNS. Overexcitability of PNS Afferent→Pin & Needles
Tingling Sensation, Efferent→Twitches, Spasm & death in
severe cases. In CNS Alkolotic→convulsion & death.
2. Enzyme Activity: Alter Protein (Enzymes inclusive) shape
& activity, therefore disturb Metab activity catalyzed by
these enzymes.
3. Influences K+ Conc.: Acidosis→↑ed H+ & ↓ed K+
Alkalosis→ ↓ed H+ & ↑ed K+ Secretion by the kidneys.
Changes in ECF[K+] conc. Can lead to cardiac
abnormalities.
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13. Acid Production in the Body
 Acids are continuously produced in the body
& they threaten the normal pH of the ECF &
ICF.
 Physiologically, acids fall into 2 groups:
1. Carbonic Acids
2. Non-carbonic or all other Acids (nonvolatile
or fixed acids
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14. Sources of Acid Production
1. Tissue Metabolism: Normal adult produces 300L of
CO2 daily.
CO2 + H2O↔ H2CO3 ↔HCO3
- + H+.
Blood pH will fall rapidly if the H2CO3 produced in the
blood from CO2 were allowed to accumulate but its
maintained by expiration as the reverse rxn occurs in
lungs.
2. CHO & Fats Metab: Incomplete oxidation of CHO
leads to formation of nonvolatile acids
• Glucose (incomplete Metab)→Lactic acid↔ Lactate- &
H+,
• Fatty acid (incomplete Oxidation)→ketone body acids.
At blood they dissociate their anion & H+.
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15. Continuations
3. Protein Metabolism: Oxidation of proteins
and amino acids produces strong acids like,
H2SO4, HCL & H3PO4.
4. Mixed diet of meat & vegetable produces
acids from protein oxidation.
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16. Homeostatic Acid-Base Balance
 Major homeostatic challenge is keeping H+
concentration (pH) of body fluids at
appropriate level
 3D shape of proteins sensitive to pH
 Diets with large amounts of proteins produce
more acids than bases which acidifies blood
 Several mechanisms help maintain pH of
arterial blood between 7.35 and 7.45
– Buffer systems, exhalation of CO2, and kidney
excretion of H+
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17. Blood pH Regulation
 Buffering is achieved by Chemical Buffers,
Lungs & Kidney.
1. Chemical Buffers: in ECF, ICF & in bone is the
1st line of defense for Blood pH.
2. Respiratory Response: the respiratory system
is the 2nd Line of Defense for Blood pH.
Breathing removes CO2 as fast as it is
produced.
3. Renal Response: The kidneys is the 3rd line of
defense of Blood pH. The burden of removing
excess H+ directly falls on the kidney.
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18. Buffer Systems/Mechanism
o The stability of pH is protected by the action of buffers.
o A pH buffer is defined as an agent that minimizes the
change in pH produced when an acid or base is added.
o A chemical buffer is a mixture of a Weak acid & its
conjugate base or vice versa
o Buffering is achieved by Chemical Buffers, Lungs &
Kidneys
– Act to quickly temporarily bind H+
– Raise pH but do not remove H+
– Most consist of weak acid and salt of that acid functioning
as weak base
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19. Chemical Buffers
The body contains many conjugate acid-base pairs
that acts as chemical buffers.
 Main ECF pair is HCO3
-/CO2 while plasma proteins &
inorganic phosphates are also ECF buffers.
 ICF have buffer stores of proteins & organic
phosphates compounds, also HCO3
- in ↓ Conc. to
ECF.
 The Bone has buffer stores of Phosphates &
Carbonate salts.
When an acid or base is added to the body, the Buffers
bind or releases H+, thereby minimizing the change in
pH.
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20. Major Chemical Buffers in the Body
Location Buffers Reaction
ECF
Bicarbonate/CO2 CO2 + H2O↔H2CO3↔H+ + HCO3
-
Inorganic Phosphate H2PO4-↔H+ + HPO4
-
Plasma Proteins (Pr) HPr ↔ H+ + Pr-
ICF
Cell Protein e.g Hb HHb ↔ H+ + Hb-
Organic Phosphate Organic- HPO4
-↔ H+ + organic-PO4
-
Bicarbonate/CO2 CO2 + H2O↔H2CO3↔H+ + HCO3
-
Bone
Mineral Phosphate H2PO4-↔H+ + HPO4
-
Mineral Carbonate HCO3
- ↔ H+ + CO3
-
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21. Phosphate Buffer
 Phosphate buffer consists of Acid-phosphate salt
(H2PO4
-) that can donate free H+ when [H+] & Basic-
phosphate salt (HPO4
2-) that can accept free H+ when
[H+] rises.
 pKa of Phosphate buffer is 6.8 closer to the blood pKa of
7.4, so it’s a good buffer. It is an important ICF buffer
because Cells contain large amts (as ATP, ADP &
Creatine Phosphate) & Intracellular pH is generally lower
than ECF pH & closer to Phosphate pH. (Cytosol =6.9)
• Important regulator of pH in cytosol
• Dihydrogen phosphate (H2PO4
-) and monohydrogen phosphate
(HPO4
2-)
• Phosphates are major anions in ICF and minor ones in ECF
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22. Protein Buffers
 Proteins are most abundant buffer pool in the
body & are excellent buffers.
 They are Amphoteric & could function as both
Acids and Bases i.e. they have ionizable groups
which can release or bind H+.
• Free carboxyl group acts like an acid by releasing H+
• Free amino group acts as a base to combine with H+
 Serum Albumin & plasma globulin
 Side chain groups on 7 of 20 amino acids also
can buffer H+
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23. Haemoglobin Buffer
 Buffers H+ generated from Metab. By-product
CO2 in transit btw the tissues & Lungs. As CO2
enters the blood, great % with H2O forms H+ &
HCO3
- catalyzed by CA in RBCs. Most H+ formed
from CO2 at tissue level bounds to reduced Hb &
no longer contributes to Body fluids acidity.
 This buffering capacity of Hb system makes the
venous blood only slightly acidic than arterial
despite high vol. of H+ & CO2 produced. The
reaction is however, reversed in the lungs.
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24. Bicarbonate/CO2 Buffer
 Very important in Acid-Base Physiology due to
i. Abundance of HCO3
- in plasma/ECF (24mmol/L) & also in ICF.
ii. Its component could be removed from or added to the body at
controlled rate despite a lower (pK=6.4) than normal Plasma
pH (7.4).
iii. It is controlled by the kidneys & Lungs
In the lungs alveoli, CO2 exist in gaseous forms & as dissolved
CO2, H2CO3, HCO3
-, CO3
-, & carbamino compounds in body
fluids.
– Based on bicarbonate ion (HCO3
-) acting as weak base
and carbonic acid (H2CO3) acting as weak acid
– Because CO2 and H2O combine to form this buffer
system, it cannot protect against pH changes due to
respiratory problems in which there is an excess or
shortage of CO2
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25. Bicarbonate/CO2 Buffer
CO2 + H2O↔H2CO3 (hydration Rxn↔Dehydration Rxn)
catalyzed by Carbonic anhydrase (Zinc
containing enzyme)
– Increase in CO2 in body fluids lowers its pH
– The Respiratory system can change the amt. of
CO2 in body fluids by hyperventilation &
Hypoventilation within minutes
– The kidney can change the amt. of HCO3
- in ECF
by forming new HCO3
- when excess acid is added
to the system or by excreting HCO3
- when excess
base is added.
• Negative feedback loop
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26. Role of Kidney in Acid-Base Homeostasis
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The kidneys play a very important role in
Acid-Base Homeostasis by excreting H+ &
retaining HCO3
-. Urine is Acidic (pH 4.5-6.0)
due to kidneys’ secretion of H+ & reabsorption
of HCO3
-, which help cushion the effect of
acidosis from body’s metabolic activities.
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27. Acidification of Urine
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 From the Bowman capsule, as urine flows
along the tubule to the Collecting duct 3
Processes occurs:
1. Filtered HCO3
- is reabsorbed
2. Titratable is formed
3. NH3 is added to the tubular urine
 Through these processes, H+ is secreted by
the tubular epithelium.
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28. Kidney Excretion of H+
 Metabolic reactions produce nonvolatile acids
 About 4,380mEq of H+ are filtered & secreted into renal
tubules & btw 50-100mEq is excreted in urine
(Acidification of Urine) while 4,280-4,330mEq is used
for the reabsorption of filtered HCO3
-.
 Secretion of H+ by 2 Pumps: (1) 2/3 Na+ /H+ [NHE3]
antiporters (PCT & CD) & (2) 1/3 ATP driven proton
pump (DCT & CD)
 A-Intercalated cells of collecting duct include proton
pumps that secrete H+ into tubule fluid
 Urine can be up to 1000 times more acidic than blood
 2 other buffers can combine with H+ in collecting duct
• HPO4
2- and NH3
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29. 29

30. Reabsorption of HCO3
-
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 Majority of HCO3
- , exit the cell via Sodium bicarbonate
cotransporter Na+ HCO3
- (NBC1-Symporter) in Basolateral
Membrane.
 Some exit the cell in exchange for Cl- via Na dependent or
non Na dependent Cl- -HCO3
- antiporters (Anion exchanger:
AE-2) in Apical Membrane.
 K+- HCO3
- symporter in the basolateral membrane may
also contribute to HCO3
- exit.
 CA is also present at the Brush border of PCT to catalyze
hydration of H2CO3 & facilitate the reabsorption of HCO3
-.
 DCT & CD reabsorb the remaining amt of HCO3
- that
escaped PCT & Henle’s Loop.
 However, B-intercalated cells in secretes HCO3
- during
metabolic alkalosis.
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31. 31

32. 32
Regulation of H+ Secretion
Factors Site of Action
↑ in H+ Secretion
Primary
- ↓ in ECF [HCO3
-] ↓pH
- ↑ in Arterial PCO2
Entire Nephron
- Cortisol
- Endothelin
Proximal Tubule
↑ in H+ Secretion
Secondary
- ↑ in filtered load of HCO3
-
- ECF vol. Contraction
- Hypokalemia
Proximal Tubule
- Angiotensis II PCT & DCT
- Aldosterone DCT & CD
- PTH (Chronic) Thick AL & DCT
↓ in H+ Secretion
Primary
- ↑ in ECF [HCO3
-] ↓pH
- ↓ in Arterial PCO2
Entire Nephron
↓ in H+ Secretion
Primary
- ↓ in filtered load of HCO3
-
- ECF vol. Expansion
- Hyperkalemia
- PTH (Acute)
CT
- Hypoaldosteronism DCT & CD

33. Cont.
 Physiologically, the primary factor that regulate H+
secretion by the nephron is a change in systemic
acid-base balance.
 Other important mediators of renal response are
cortisol & endothelin.
 Endothelin-1 produced by Endothelial & PCT cells is
↑ed with acidosis stimulating phosphorylation &
subsequent insertion of the Na+-H+ antiporter into the
apical membrane & insertion of the 1Na+-3HCO3-
symporter into the basolateral membrane.
 Acidosis also stimulate Cortisol secretion which acts
on the kidneys to ↑ transcription of Na+-H+ antiporter
& 1Na+-3HCO3- symporter genes in the PCT, as well
as ↑ translation of the mRNA of these transporters.
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34. Cont.
 Na+ balance changes ECF vol. & affects H+ secretion.
Aldosterone & Angiotensin II affect H+ secretion via this
relationship.
 PTH has both inhibitory & stimulatory effect on H+
secretion. Acute PTH secretion, inhibits H+ secretion by
PCT by inhibiting the activity of the Na+-H+ antiporter & by
also causing the antiporter to be endocytosed from the
apical membrane. Long-term/Chronic PTH stimulates renal
acid excretion by acting on the thick ascending limb of
Henle's loop & DCT.
 Hypokalemia stimulates & hyperkalemia inhibits H+
secretion. K+ induced changes in ICF pH is liable for this
effect. ↓ K+=Acidifying & ↑ed K+=Alkalanizing the cells. 34

35. Closing Remarks and
Questions

36. Closing Remarks
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37. Questions?
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