Activities of almost all enzyme systems within the body are influenced by hydrogen ion (H+) concentration. Substances that release H+ are acids and substances that tend to receive H+ are bases. The kidneys control acid-base balance by secreting acidic or basic urine. HCO-3 is continuously filtered in tubules - if excreted into urine, it removes base from the blood. There are three main mechanisms to regulate H+ concentration in the body: chemical buffers, the respiratory system, and the renal system. The kidneys play the most important role by secreting H+ into tubules, reabsorbing HCO-3, and producing new HCO-3.

1. Regulation of blood pH
Activities of almost all enzyme systems within body are
influenced by H+
concentration. Substances that release H+
are referred as Acids and substance that tendency to receive
H+
are referred to as Bases. H+
is single free proton released
by hydrogen atom.
HCl Ionization
H+
+Cl-
H2CO3
Ionize in water
H+
+CO-
3
Carbonic Acid Hydrogen ion+ Bicarbonate ions
Some proteins also function as bases. Some of the amino
acids that make up proteins have positive charges and
readily accept hydrogen ion. Hemoglobin in blood is
important among body’s bases. pH is inversely proportional
to Hydrogen ion therefore:
Low pH corresponds to high H+
and
High pH corresponds to low H+
pH values
Medium pH Impact
Arterial Blood 7.4 If decreases causes Acidosis*
Venous Blood 7.35 If increases causes Alkalosis**
Interstitial Fluid 7.35
Intra cellular 6-7.4
Urine 4.5-8
HCl 0.8
*at the pH of 6.8 (acidosis), individual can live more than few
hours.
**at the pH of 8.0 (alkalosis), individual can live more than
few hours.
Venous blood has high pH due to extra amount of CO2. While
interstitial fluids have high pH as compare to the intracellular
pH as shown below
CO2 + H2O Carbonic anhydrase
H2CO3
Ionize in water
H+
+HCO-
3
Carbondioxide released by body tissues combine with water
by the help of carbonic anhydrase enzyme and farms
carbonic acids which ultimately ionized to form hydrogen ion
GENERAL PRINCIPLES OF PHYSIOLOGY
PHYS- 701
Topic
Homeostasis
Regulation of
blood pH
Mubasher Solangi
M.Phil (Pursuing)
Supervisor
Dr. Moolchand Malhi, PhD
Assistant Professor
Dept: of Physiology & Biochemistry
Faculty of A.H and Veterinary Sciences
SAU Tando Jam
pH
Activities of almost all enzyme
systems within body are influenced
by H+
concentration. Substances that
release H+
are referred as Acids and
substance that tendency to receive H+
are referred to as Bases. H+
is single
free proton released by hydrogen
atom.
Kidneys control acid-base balance by
secreting acidic or basic urine. HCO-
3 are filtered continuously in tubules,
if excreted into urine it removes base
from blood.
29/02/2016

2. Editor: Mubasher Solangi, M.Phil (Pursuing)
Supervisor: Dr. Moolchand Malhi, PhD
General Principles of Physiology (PHYS-701)
Assignment | Homeostasis, Blood pH Regulation
2
Department of Physiology and Biochemistry, Faculty of Animal Husbandry and Veterinary Sciences
Sindh Agriculture University Tando Jam
and bicarbonate ions. Increase in H+
concentration, decrease in pH of interstitial fluids
Intracellular pH
Intra cellular pH is slightly lower than plasma pH. During metabolism of cells they produce carbonic acid
depending upon type of cells. As discussed earlier Carbonic acid ionizes to form hydrogen ion and
bicarbonate ions ultimately give rise to H+
concentration which means lower pH as compare to plasma.
pH of urine
pH of urine ranges from 4.5 to 8.0 depending upon acid-base balance of extracellular fluid. HCl is
extreme acid body fluid having pH of 0.8. it is secreted by oxyntic (parietal) cells of stomach mucosa.
Defense against changes of H+
in body
There are three basic mechanisms to control hydrogen ion concentration (pH) within body.
1. Chemical acid base buffer system
2. Respiratory System
3. Renal System
Chemical acid base buffer
system
Respiratory System Renal System
 React within fraction of
seconds

Don’t add or eliminate H+
 Only keep them tied until
acid base balance is re-
established
 Acts within few minutes
 Eliminate CO2 and therefore
H2CO3 from body
 Acts in hours to days
 Most powerful mechanism
 Secretes H+
, reabsorbs and
produce HCO-
3
First two mechanisms keep H+ concentration from changing too much until the third line of action gets
in action.
Renal Control of acid base balance
Kidneys control acid-base
balance by secreting acidic or
basic urine. HCO-3 are
filtered continuously in
tubules, if excreted into
urine it removes base from
blood.

3. Editor: Mubasher Solangi, M.Phil (Pursuing)
Supervisor: Dr. Moolchand Malhi, PhD
General Principles of Physiology (PHYS-701)
Assignment | Homeostasis, Blood pH Regulation
3
Department of Physiology and Biochemistry, Faculty of Animal Husbandry and Veterinary Sciences
Sindh Agriculture University Tando Jam
H+ ions are secreted into tubules by epithelial cells of lumen thus removing acid from blood. Non
volatile acids are excreted beside this excretion and during
the excretion of non volatile acids kidneys also prevent loss of
bicarbonates in urine. Those non volatile acids are produced
during metabolism of proteins and cannot be excreted by
lungs.
Re absorption of carbonate and excretion of H+
by kidney
Re absorption of carbonate and excretion of H+
is
accomplished through the process of H+
secretion by the
tubules
HCO-
3 + H+
H2CO3
Here HCO-
3 is filtered by the tubules at different stages and H+
is secreted by the lumen of tubules. This re absorption of
HCO-
3 and secretion of H+
occurs in almost all parts of tubules
except ascending and descending thin limbs of loop of Henle.
There are three basic mechanisms to regulate H+
concentration in extracellular fluid are as follows.
1. Secretion of H+
2. Re absorption of HCO-
3
3. Production of HCO-
3
Secretion of H+
Cellular Mechanism for; (1) active secretion of
hydrogen ions into the renal tubules, (2) tubular
reabsorption of bicarbonate ions, (3) sodium ion
reabsorption in exchange for hydrogen ion secreted.
This pattern of hydrogen ion secretion occurs in
proximal tubules, thick ascending segment of the loop
of Henle and the early distal tubule.
 Secretion of H+
takes place by sodium hydrogen counter transport mechanism as follows
 CO2 is formed by metabolism in tubular epithelial cells or diffuses from collecting ducts into the
tubular cells.

4. Editor: Mubasher Solangi, M.Phil (Pursuing)
Supervisor: Dr. Moolchand Malhi, PhD
General Principles of Physiology (PHYS-701)
Assignment | Homeostasis, Blood pH Regulation
4
Department of Physiology and Biochemistry, Faculty of Animal Husbandry and Veterinary Sciences
Sindh Agriculture University Tando Jam
 CO2 combines with water molecule to form Carbonic acid with the help of carbonic anhydrase
enzyme, which dissociates into hydrogen and bicarbonate ions.
 Hydrogen ion produced than bind to the carrier protein called sodium hydrogen exchanger
protein and is ready to be transported from tubular lumen.
 At the same time sodium outside binds with carrier protein to enter into the tubular cell thus
facilitating the hydrogen ion by making Na+ gradient inside. For this movement energy derived
from sodium gradient produced by Na+
facilitating H+
going out of lumen.
 Na+
gradient is developed by Sodium potassium ATPase pump in basolateral membrane of
tubular cell.
 When H+
moves out of the cell through tubular lumen, HCO-
3 downhill through basolateral
membrane, thus we can say for every H+
secreted into the tubular lumen an HCO-
3 enters the
blood.
Active secretion of H+
Primary active secretion of hydrogen ion
through the luminal membrane of intercalated
epithelial cells of the late distal and collecting
tubules.
Secretion of H+
takes place in distal, convoluted tubules and in collecting ducts. The secretion is
facilitated by hydrogen-transporting ATPase (a specific protein). About 5% of total H+
secretion takes
place here which makes urine more acidic. Bicarbonate ion is absorbed for each hydrogen ion secreted,
and a chloride ion is passively secreted along with the hydrogen ion.
Re absorption of HCO-
3
 Secretion of H+
(by dissociation of HCO-
3) takes place in tubular cells into renal tubules.
 Formation of carbonic acid by H+
and HCO-
3 (filtered)
 Dissociation of HCO-
3 in CO2 and H2O and diffusion of CO2 into tubular cell
 By the action of carbonic anhydrase enzyme CO2 combines H2O to form H2CO3 again.
 H2CO3 ionize to form H+ and HCO-
3, in this way HCO-
3 enters the interstitial fluid crossing
basolateral membrane, taken into the peritubular capillary blood.

5. Editor: Mubasher Solangi, M.Phil (Pursuing)
Supervisor: Dr. Moolchand Malhi, PhD
General Principles of Physiology (PHYS-701)
Assignment | Homeostasis, Blood pH Regulation
5
Department of Physiology and Biochemistry, Faculty of Animal Husbandry and Veterinary Sciences
Sindh Agriculture University Tando Jam
 Thus at each H+
secretion an HCO-
3 enters to the blood.
Production of new HCO-
3
Buffering of secreted hydrogen ions by filtered
phosphate; New bicarbonate ion is returned to
the blood for each NaHPO-
4 that reacts with the
secreted hydrogen ion.
 H+ and HCO-
3 titrated each time but H+
secretion is relatively more as compare to HCO-
3
formation in tubular cell.
 When H+
secreted in larger amount, small number of H+
can be excreted in ionic form via urine,
the reason is that:
 Filtration has some other buffers like phosphate buffer and ammonia buffer (Urete and citrate
buffers are much less important)
 When H+
secreted in large amount as titration rate, it combines to ammonia buffer or
phosphate buffer.
 Process of formation of H+
is same as discussed earlier, (upon formation of each H+
an HCO-
3 is
produced.)
 When H+
transported to tubular lumen and binds with buffers other than HCO-
3, HCO-
3
transported to interstitial fluid through basal membrane which is said to produce by tubular cell.
BIBLIOGRAPHY:
Title Text book of Medical Physiology, 11
th
ed.
Author Arthur C, M.D. Guyton and J.E. Hall
Publication Date 2006
Publisher SAUNDERS, An imprint of Elsevier
ISBN# 13: 978-07216-0240-0
10: 0-07216-0240-1
Title Text book of Animal Physiology
Author Lauralee Sherwood, Hillar Klandorf and paul H. Yancey
Publication Date 2008
Publisher Cengage Learning India Pvt. Ltd.
ISBN# 10: 81-315-1267-3
13: 978-81-315-1267-8