12.

ANATOMY &
PHYSIOLOGY OF
URINARY TRACT 7
Prof. Dr. Nadia Yassin
 ACID-BASE BALANCE
ILOS
 Differentiate between the different regulatory defense
mechanisms for the maintenance of the PH of the blood.
 Differentiate between different chemical buffers in the
body and their prominent effects in special
compartments of the body:
 Chemical buffer
 Respiratory regulation
 Renal regulation

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 ACID-BASE BALANCE
 Importance of Acid-Base Balance Regulation:
To provide an optimal environment for many processes which depend on
pH, e.g., enzymes.
 Acids in the Body:
Two types of acids are produced in the body:
1. Volatile Acids: H2CO3
- In the presence of carbonic anhydrase
CO2 + H2O H2CO3 H+ + HCO3-.
- CO2 is volatile & can be excreted by the lungs.
- It is produced by aerobic metabolism in cells.
2. Nonvolatile Acids (= Fixed Acids):
- They include, e.g.,
 Sulfuric acid from oxidation of sulfur-containing amino acids in
proteins.
 Phosphoric acid from catabolism of phospholipids.
 Lactic acid from anaerobic metabolism of glucose during exercise.
 Acetoacetic acid & -hydroxybutyric acid from incomplete
oxidation of fatty acids in diabetes mellitus. 3
 ACID-BASE BALANCE (cont.)
 pH in Blood:
 Arterial Blood: 7.4
 Venous blood & I.C.F.: 7.35
 Normal range = 7.4 ± 0.05
More than 7.4  alkalosis
Less than 7.35  acidosis
It becomes rapidly fatal if pH is ≥ 8.0 or ≤ 6.8.

 Regulation of pH:
I. Chemical Buffer System: effective within a fraction of a second
II. Respiratory Regulation: effective within minutes - one day
III. Renal Regulation: effective within hours - days.

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 I. CHEMICAL BUFFERS
= 1ST LINE OF DEFENSE (cont.)
 Definitions:
 Buffer: is a weak acid associated with the salt of its conjugate base.
They form an acid-base pair: HA & Na+A- (or K+A-).
 Acid: is a molecule that can release hydrogen ions in solution.
 Base: is an ion or a molecule that can accept hydrogen ions.

 What is a “weak” or a “strong” acid?

Weak acid: binds H+ ions more strongly & causes little change in pH, e.g.,
H2CO3.
Strong acid: binds H+ ions loosely, i.e., dissociates easily, leaving free H+
ions that change the pH markedly, e.g., H2SO4 & HCl.

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 I. CHEMICAL BUFFERS
= 1ST LINE OF DEFENSE (cont.)
 Function of buffers:
A buffer minimizes the changes in pH of solutions when either an acid or
an alkali is added.
Buffer systems do not eliminate H+ from the body or add them to the body.
They only keep them tied up until balance can be reestablished, e.g.,

NaCl + H2CO3  HCl + NaHCO3

(weak acid) H2CO3 + NaOH  NaHCO3 + H2O
(neutral salt)
N.B.
 pH = log 1/[H+]
 pH is inversely related to hydrogen ion concentration.
 a low pH corresponds to a high hydrogen ion concentration &
vice versa.
 pH 4 is a 1000 x stronger acid than pH 7.
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 I. CHEMICAL BUFFERS
= 1ST LINE OF DEFENSE (cont.)

 Henderson-Hasselbalch Equation:

[salt]
pH = pK + log
[acid]

- pK is the dissociation constant of a particular acid.

- When the concentrations of salt & acid are equal, the pH = pK (as log 1
= zero). This is the pH at which this buffer system works optimally.

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 I. CHEMICAL BUFFERS
= 1st LINE OF DEFENSE (cont.)

 Effectiveness of a buffer depends on:

1. The pH the buffer has to preserve:
Maximal effectiveness of a buffer is when the pH it has to defend is
equal to its pK.
 pK for bicarbonate buffer = 6.1
 pK for phosphate buffer = 6.9.

2. The amount of buffer present:

The greater the amount of a buffer, the more effective it is.
If there is a large amount of a buffer:
 Addition of an acid  many H+ ions can be absorbed.
 Addition of an alkali  many H+ ions can be liberated.

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 I. CHEMICAL BUFFERS
= 1ST LINE OF DEFENSE (cont.)
 Buffers in the Body: NaHCO3
1. Bicarbonate-carbonic acid buffer system:
H2CO3
- Since carbonic acid can spontaneously transform
into CO2, the buffer pair can also be written as NaHCO3/CO2.
- Its pK = 6.1
- Based on its pK alone, this buffer is a bad buffer for blood, as it is
1.3 units away from the pH which it has to defend. But, in fact, this
buffer is a major ECF buffer, because:
1. It is always readily available, as CO2 is continuously produced by
metabolic processes of the body.
2. Its concentration is well regulated, since lungs & kidneys control
the two components of the buffer pair:
 Lungs: handle CO2
 Kidneys: handle HCO3-.
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 I. CHEMICAL BUFFERS
= 1ST LINE OF DEFENSE (cont.)
Buffers in the Body: (cont.) Na2HPO4
2. Phosphate buffer system:
NaH2PO4
- Its pK = 6.9
- Based on its pK alone, this buffer is a good buffer for blood (close to
pH of ECF). Yet, its concentration is low (1/12 that of the bicarbonate
system)  It is a minor ECF buffer.
- It is a good buffer in 2 sites:
1. In ICF: Its concentration is high inside cells.
2. In tubular fluid: (most important urinary buffer)
a. phosphates are concentrated in tubular fluid.
b. pH of urine is more acidic  closer to pK of this system than
blood.

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 I. CHEMICAL BUFFERS
= 1ST LINE OF DEFENSE (cont.)
Buffers in the Body: (cont.) R-COONa KHb
3. Protein buffer system: or or
- pH of blood is 7.4, i.e., slightly alkaline.R-COOH HHb
- In alkaline medium, proteins act as weak
acids. When they dissociate, they give free H+ & proteinate ions.
- Their pK is within the physiologic pH range.
- The protein buffer system includes plasma proteins & hemoglobin.
- Reduced Hb is a better buffer than oxygenated Hb (see respiration).
N.B. The buffering power of Hb is 6 x more powerful than that of plasma
proteins.

Principal Buffers of the Body:

 In blood: bicarbonate, plasma proteins, hemoglobin
 In ICF: proteins, phosphate
 In interstitial fluid: bicarbonate. 11
 II. RESPIRATORY REGULATION OF pH
= 2nd LINE OF DEFENSE
 This system starts to work within minutes.
 The respiratory system controls pH of body fluids by controlling PCO2 in
blood:
  PCO2   H2CO3   H+ = acidic pH
  PCO2   H2CO3   H+ = alkaline pH.

 Two factors affect PCO2:

1. Rate of metabolic CO2 formation:
  metabolism   PCO2   H+ = acidic pH
  metabolism   PCO2   H+ = alkaline pH.
2. Rate of pulmonary ventilation:
  ventilation rate  washing out of CO2   pH (alkaline)
  ventilation rate  accumulation of CO2   pH (acidic).

At the same time:

 Acidosis  stimulates respiratory center   rate of ventilation   pH.
 Alkalosis  inhibits respiratory center   rate of ventilation   pH.

The respiratory system has 1-2 x the buffering power of all chemical buffers
together. 12
 III. RENAL REGULATION OF pH
= 3rd LINE OF DEFENSE

 The kidneys take hours or days to change the pH. But renal correction of
acid-base disturbances is more complete than respiratory correction.
 The kidneys regulate blood pH by controlling plasma bicarbonate
concentration by secreting either acidic or alkaline urine.
 Normally, kidneys are responsible for getting rid of acids produced by the
metabolism of food stuffs in the body.
 In blood, strong acids are first neutralized by chemical buffers, esp. the
bicarbonate system   plasma bicarbonate concentration.

Thus, kidneys have 2 functions to restore the acid-base balance:

1. To reabsorb filtered bicarbonate.
2. To excrete H+ ions.

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 III. RENAL REGULATION OF pH
= 3rd LINE OF DEFENSE
1. Reabsorption of filtered bicarbonate:
Bicarbonates are continuously filtered by the glomeruli. They are mostly
reabsorbed in PCT.
Mechanism:
Bicarbonate in the lumen cannot diffuse readily into tubular cells. Thus,
HCO3- ions are reabsorbed by a special process:
 In the lumen: The luminal brushborder of the PCT cell is the only one in
renal tubules containing carbonic anhydrase (CA). H+ ions secreted into
PCT lumen by Na+-H+ exchange combine with filtered HCO3- in the
presence of CA to form carbonic acid. Carbonic acid then is converted to
CO2 & H2O, which diffuse into the PCT cell.
 In the PCT cells:
Intracellular CA catalyzes the reaction CO2 & H2O  H2CO3  H+ &
HCO3-. H+ is secreted into the lumen via the Na+-H+ exchange
mechanism in the luminal membrane, while HCO3- is reabsorbed via
basolateral membrane into the interstitium. The secreted H+ starts a new
cycle.
 Thus, each time a H+ ion is formed in tubular epithelial cells, a HCO3- ion
is also formed & reabsorbed back into blood. The result is net 14
-
reabsorption of filtered HCO , but there is no net excretion of H . +
Reabsorption of filtered bicarbonate

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 III. RENAL REGULATION OF pH
= 3rd LINE OF DEFENSE (cont.)
2. Excretion of H+:
It takes place in DCT and CD.
H+ ions are excreted by 2 mechanisms: as titrable acid & as NH4+.
A. Excretion of H+ as titrable acid (H2PO4- ):
 In tubular cells:
H+ & HCO3- are produced in the cell from CO2 & H2O. The H+ is secreted
by H+-ATPase into the lumen & the HCO3- is reabsorbed into the blood
(“new” HCO3-).
 In tubular lumen:
The secreted H+ combines with filtered HPO42- to form H2PO4-, which is
excreted as titrable acid.
 This process results in net excretion of H+ & net reabsorption of
newly synthesized HCO3-.
 As a result of H+ secretion, the pH of urine becomes progressively lower.
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Excretion of H+ as titrable acid

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 III. RENAL REGULATION OF pH
= 3rd LINE OF DEFENSE (cont.)
2. Excretion of H+: (cont.)
B. Excretion of H+ as ammonium (NH4+):
 In tubular cells:
NH3 (ammonia) is produced by renal cells from glutamine. It diffuses
down its concentration gradient from the cells into the lumen.
H+ & HCO3- are produced from CO2 & H2O. The H+ ion is secreted by
H+-ATPase into the lumen, while the HCO3- ion is reabsorbed into blood
(“new” HCO3-).
 In tubular lumen:
H+ combines with NH3 to form NH4+, which is excreted.

 This process also results in net excretion of H+ & net reabsorption of

newly synthesized HCO3-.

N.B. H2PO4- is termed titrable acid, because it liberates its H+ if the urine is
titrated back to plasma pH, while NH4+ gives up little of its H+, as the pK
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of the ammonia buffer system is 9.0.
Excretion of H+ as NH4+

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 III. RENAL REGULATION OF pH
= 3rd LINE OF DEFENSE (cont.)
Limiting pH:
- Since H+ ions are secreted into tubular fluid in large amount, pH may 
markedly.
- pH changes in urine range from: 4.5 – 8.0.
- Below a pH of 4.5, the urinary transport systems cannot work.
 It is called the “limiting pH”.
- With continuous secretion of H+ ions by the kidneys (esp. in acidosis),
the limiting urinary pH would be reached rapidly & the total amount of
H+ secreted would be small if there were no buffers in the urine that
“tied up” H+.
- However, secreted H+ reacts with HCO3- to form CO2 & H2O, with
HPO42- to form H2PO4- & with NH3 to form NH4+.
- In this way, large amounts of H+ can be secreted, & with every H+ ion
secreted, a HCO3- ion is returned to (in the case of bicarbonate
reabsorption) or added to the depleted body stores.
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