Mia Kusmiati

Department of Biochemistry
 The chemical processes represent the first
line of defense to an acid or base load
and include the extracellular and
intracellular buffers
 The physiologic processes modulate acid-

base composition by changes in cellular

metabolism and by adaptive responses in
the excretion of volatile acids by the lungs
and fixed acids by the kidneys

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 The task imposed on the mechanisms
that maintain Acid-Base homeostasis is
large

◦ Metabolic pathways are continuously

consuming or producing H+

◦ The daily load of waste products for

excretion in the form of volatile and
fixed acids is substantial

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1. Chemistry buffer of Body fluid:
React very rapidly
(less than a second)
2. Respiration system  quick and brief,
Reacts rapidly (seconds to minutes)

3. Renal system low respon but long efect,

minutes to hours
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 Chemical Buffers
◦ The body uses pH buffers in the blood to guard
against sudden changes in acidity
◦ A pH buffer works chemically to minimize changes in
the pH of a solution
H+
OH-
H+

Buffer OH-
OH-
H+
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 Respiratory Regulation
◦ Carbon dioxide is an important by-product
of metabolism and is constantly produced by
cells
◦ The blood carries carbon dioxide to the
lungs where it is exhaled

Cell
CO2CO2CO
CO2 CO 2
CO2 2
Metabolism

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 Respiratory Regulation
◦ When breathing is increased,
the blood CO2 level
decreases and the blood
becomes more Base
◦ When breathing is decreased,
the blood CO2 level
increases and the blood becomes more
Acidic
◦ By adjusting the speed and depth of
breathing, the respiratory control centers
and lungs are able to regulate the blood pH
minute by minute
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 Kidney Regulation
◦ Excess acid is excreted by
the kidneys, largely in the
form of ammonia

◦ The kidneys have some

ability to alter the amount
of acid or base that is
excreted, but this
generally takes several
days

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 Physiologically important acids include:
◦ Carbonic acid (H2CO3)
◦ Phosphoric acid (H3PO4)
◦ Pyruvic acid (C3H4O3)
◦ Lactic acid (C3H6O3)
 These acids are dissolved in body fluids

Phosphoric acid
Lactic acid

Pyruvic acid

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 Physiologicallyimportant bases include:
◦ Bicarbonate (HCO3- )
◦ Biphosphate (HPO4-2 )

Biphosphate

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Carbonic anhidrase (CA):
a.Alveolar
b.Epitel tubulus
c.Endotel capilar
 pH changes have dramatic effects on
normal cell function
◦ 1) Changes in excitability of nerve and
muscle cells
◦ 2) Influences enzyme activity
◦ 3) Influences K+ levels

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 When reabsorbing Na+ from the filtrate
of the renal tubules K+ or H+ is secreted
(exchanged)
 Normally K+ is

secreted in much
greater amounts
than H+

K+
Na+

H+

K+
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 IfH+ concentrations are high (acidosis)
than H+ is secreted in greater amounts
 This leaves less K+ than usual excreted
 The resultant K+ retention can affect

cardiac function and other systems

K+
Na+

H+

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 pH= pKa + log (HCO3 - ) / (H2CO3)

Concentration of H2CO3 cannot be measured

directly in blood. So it is calculated by
multiplying the pCO2 and solubility constant. 
1. Elimination of non volatile acids ,Lactic
acids, H₂SO₄ buffered with cations (Na⁺ ) are
removed by glomerular filtration
2. (Na⁺ ) ↔ H⁺ across tubular membrane to
prevent loss of Na⁺
 H⁺secretion, NaHCO₃ recovery
 Loss of Na⁺ is prevented by : a) Bicarbonate
mechanism b) Phosphate mechanism c) Ammonia
mechanism
3. HCO³⁻ reabsorption
4. NH₃ production
Factorsaffecting bicarbonate reabsorption
in proximal renal tubular cells
1. pCO₂
2. Concentration of K⁺ in ICF ( intracellular fluid )
3. Plasma Concentration of Cl⁻
4. Concentration of adreno-corticoids Hormones
 Acidosis and Alkalosis can arise in two
fundamentally different ways:
◦ 1) Excess or deficit of CO2
(Volatile Acid)
 Volatile Acid can be eliminated by the
respiratory system
◦ 2) Excess or deficit of Fixed Acid
 Fixed Acids cannot be
eliminated by the
respiratory system

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 Normal values of bicarbonate
(arterial)
◦ pH = 7.4
◦ PCO2 = 40 mm Hg
◦ HCO3- = 24 meq/L

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 CARBON DIOXIDE DIFFUSION
Red Blood Cell Systemic Circulation
Plasma

Cl-
carbonic (Chloride Shift)
anhydrase
CO2 + H2O H+ + HCO3-
HCO3-
CO2 diffuses into the plasma and into the RBC

Within the RBC, the hydration of CO2 is catalyzed

CO2 by carbonic anhydrase

CO2 Bicarbonate thus formed diffuses into plasma

Tissues 25
 Red Blood Cell Pulmonary Circulation
Plasma

Cl-
HCO3-
CO2 + H2O H+ + HCO3-

CO2 Bicarbonate diffuses back into RBC in pulmonary

capillaries and reacts with hydrogen ions to form
carbonic acid

The acid breaks down to CO2 and water

Alveolus
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 Red Blood Cell Pulmonary Circulation
Plasma

Cl-

CO2 + H2O + HCO3-

CO2 H+

Alveolus
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 Caused by hyperkapnia due to
hypoventilation
◦ Characterized by a pH decrease
and an increase in CO2
pH
CO2 CO2
CO2 CO2
CO CO2
2 CO2
COCO
2 2 CO2 CO2
pH CO2
CO2
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 Hypo = “Under”

Elimination of CO2

H +

pH 29
 Hyperkapnia is defined as an
accumulation of carbon dioxide in
extracellular fluids

pH
CO2 CO2
CO2 CO2
CO CO2
2 CO2
COCO
2 2 CO2 CO2
pH CO2
CO2
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 Hyperkapnia is the underlying cause of
Respiratory Acidosis
◦ Usually the result of decreased CO2
removal from the lungs

pH
CO2 CO2
CO2 CO2
CO CO2
2 CO2
COCO
2 2 CO2 CO2
pH CO2
CO2
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 Respiratory acidosis
develops when the
lungs don't expel CO2
adequately
 This can happen in

diseases that severely

affect the lungs, such as
emphysema, chronic
bronchitis, severe
pneumonia, pulmonary
edema, and asthma
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 Decreased CO2 removal
can be the result of:
1) Obstruction of air
passages
2) Decreased respiration
(depression of
respiratory centers)
3) Decreased gas
exchange between
pulmonary capillaries
and air sacs of lungs
4) Collapse of lung
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 Buffering systems provide an immediate
response to fluctuations in pH
◦ 1) Phosphate
◦ 2) Protein
◦ 3) Bicarbonate Buffer System

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A buffer is a combination of chemicals
in solution that resists any significant
change in pH
 Able to bind or release free H+ ions

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 Hemoglobin buffers H+ from metabolically
produced CO2 in the plasma only
 As hemoglobin releases O it gains a great
2
affinity for H+

O2 O2

Hb
O2 O2

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 H+ generated at the tissue level from the
dissociation of H2CO3 produced by the
addition of CO2
 Bound H+ to Hb (Hemoglobin) does not

contribute to the acidity of blood

O2 O2

Hb
O2 O2

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 As H+Hb picks up O2 from the lungs the Hb
which has a higher affinity for O2 releases
H+ and picks up O2
 Liberated H+ from H O combines with
2
HCO3-

HCO3- H2CO3 CO2 (exhaled)

O2 H+

Hb
O2 O2
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 A more important urine-buffering system to
secreted H+ than phosphate.
 Producing ammonia is enhanced by an acid
load and hypokalemia
 NH4 is trapped in the lumen DCT and
excreted as the salt Chloride.
 The kidney can adjust the amount of NH3
synthesized to meet demand  powerful system to
buffer secreted H+
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 The Glutaminase hydrolyse the Glutamine to
ammonia and Glutamic acid.
 The ammonia diffuses in lumen and combine

with H+ to form NH4 + and excreted.

 In acidosis, glutaminase activity increases and

excreate a lot of acids by urine.

 The increased activity takes about 3-4 days

to set in under condition of acidosis but once

established it can eliminate acids up to 400
meq/day (normal 70 meq/day
 Capillary Distal Tubule Cells

NH2

NH
NH3 3 H+
WHAT
HAPPENS
NEXT?
Tubular urine
to be excreted

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Capillary Distal Tubule Cells Notice the
H+ - Na+
NH3 exchange to
maintain
electrical
neutrality
Dissociation of
carbonic acid
NaNaCl
+
+ Cl-
H2CO
HCO 3 +3 H
- +

NaHCO3
NH3Cl-
NH4Cl
Click
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to to
Start
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Animation
Animation
Again Tubular Urine
43
Capillary Distal Tubule Cells Notice the
H+ - Na+
NH3 exchange to
maintain
electrical
neutrality

NaNaCl
+
+ Cl-
H2CO
HCO 3 +3 H
- +

NaHCO3
NH3Cl-
NH4Cl
Click
Click
Mouse
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to to
Start
See
Animation
Animation
Again Tubular Urine
44