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AZRA NAHEED MEDICAL COLLEGE
DEPARTMENT OF PHYSIOLOGY
DR.TAYYABA AZHAR
30-Apr-17
1
INTRODUCTION
• Kidney plays an important role in maintenance
of acid base balance by excreting hydrogen ions
and retaining bicarbonate ions.
• Normally, urine is acidic in nature with a pH of
4.5 to 6.
• The metabolic activities in the body produce lot
of acids (with lot of hydrogen ions) which
threaten to push the body towards acidosis.
However, kidneys prevent this by excreting
hydrogen ions (H+) and conserving bicarbonate
ions (HCO3~).
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INTRODUCTION
• Conservation or reabsorption of HCO 3~ is an
important process because of the high quantity of
filtered HCO3- .
• About 4320 mEq of HCO3~ is filtered by the
glomeruli of kidneys everyday. It is called filtered
load of HC03~.
• Excretion of this much HCO 3~ through urine will
affect the acid base balance of body fluids. So,
HCO3~ must be taken back from the renal tubule
by reabsorption.
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INTRODUCTION
• The reabsorption of filtered HCO 3~ utilizes
secretion of H+ in the renal tubules.
• About 4380 mEq of H + appear every day in the
renal tubule by means of filtration and secretion.
• Not all the H+ pass through in urine. Out of 4380
mEq, about 4280 to 4330 mEq of H + is utilized
for the reabsorption of filtered HCO 3~. Only the
remaining 50 to 100 mEq is excreted.
• It results in the acidification of urine.
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SECRETION OF HYDROGEN IONS
• Secretion of H+ into the renal tubules occurs
by the formation of carbonic acid. Carbon
dioxide formed in the tubular cells combines
with water to form carbonic acid.
• Carbon dioxide enters the cells from tubular
fluid also. Carbonic anhydrase is essential for
the formation of carbonic acid. This enzyme
is available in large quantities in the epithelial
cells of the renal tubules. The carbonic acid
immediately dissociates into H+ and HCO3~.
ACIDIFICATION OF URINE
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SODIUM-HYDROGEN ANTIPORT PUMP
• Sodium ion (Na+) is reabsorbed from the
tubular fluid into the tubular cell, H + is
secreted from the cell into the tubular fluid in
exchange for Na+.
• The sodium-hydrogen antiport pump present
in the tubular cells is responsible for the
exchange of Na+ and H+.
• This type of sodium-hydrogen counter
transport occurs predominantly in distal
convoluted tubule.
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ATP DRIVEN PROTON PUMP
• In addition to sodium-hydrogen antiport pump, one
more mechanism is present in distal convoluted
tubule and collecting duct for the secretion of H +.
• Distal convoluted tubule and collecting duct are
made up of two types of epithelial cells namely,
principal cells (P cells) and intercalated cells (I
cells).
• The P cells contain a pump called proton pump that
transports the H+ from tubular cells into the tubular
lumen. This pump operates by energy liberated from
breakdown of ATP.
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ACIDIFICATION OF URINE
• The kidneys control acid-base balance
by excreting either an acidic or a
basic urine.
• The mechanism by which slightly
alkaline glomerular filtrate is
converted into acidic urine is called
Acidification of urine.
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PRINCIPLES OF URINE ACIDIFICATION
1. Secretion of H+ in exchange of cation
usually Na+.
2. Conservation of HCO3- in the body fluid.
3. Secretion of NH3 into the tubular fluid.
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REMOVAL OF H+ & ACIDIFICATION OF
URINE
The H+, which enters the renal tubules by
filtration and secretion, is removed by three
mechanisms:
1. Bicarbonate (HCO3-) mechanism.
2. Phosphate (HPO4-) mechanism.
3. Ammonia (NH3) mechanism.
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SECRETION OF HYDROGEN IONS
• H+ from the tubular cells are secreted into
the lumen of proximal convoluted tubule,
distal convoluted tubule and collecting duct.
• There are two mechanisms for the secretion
of H+:
1. Sodium-Hydrogen antiport pump.
2. ATP driven proton pump.
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BICARBONATE MECHANISM
• All the filtered HCO 3~ into the renal tubules
is reabsorbed.
• About 85% of it is reabsorbed in proximal
convoluted tubule; 10% in DCT and 5% in
CT.
• The reabsorption of HCO 3~ utilizes the H+
present in renal tubules.
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H+ SECRETION
• H+ comes from
cellular H2CO3.
• So, H+ is secreted
and one Na+ and
one HCO3- enter
in the ISF.
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H+ SECRETION
1. Primarily H+
secretes with Na+H+ pump.
2. Na+ goes to ISF &
K+ enters into the
cell by Na+K+
pump. Due to
lower intracellular
Na+ again enters in
the cell with
secretion of H+.
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REABSORPTION OF BICARBONATE
• Reabsorption of bicarbonate
in different segments of the
renal tubule.
• The percentages of the
filtered load of bicarbonate
absorbed by the various
tubular segments are shown,
as well as the number of
milliequivalents reabsorbed
per day under normal
conditions.
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BICARBONATE MECHANISM
• The H+ secreted into the renal tubule,
combines with filtered HCO 3~ forming
carbonic acid.
• Carbonic acid dissociates into carbon
dioxide and water in the presence of
carbonic anhydrase. Carbon dioxide and
water enter the tubular cell.
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BICARBONATE MECHANISM
• In the tubular cells, carbon dioxide combines with water to
form carbonic acid.
• It immediately dissociates into H + and HCO3~. HCO3~ from
the tubular cell enters the interstitium. There it combines
with Na+ to form NaHCO3.
• Now, the H+ is secreted into the tubular lumen from the cell
in exchange for Na+.
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BICARBONATE MECHANISM
Thus, for every hydrogen ion secreted into
lumen of tubule, one bicarbonate ion is
reabsorbed from the tubule. In this way, kidneys
conserve the HCO3~. The reabsorption of
filtered HCO3~ is an important factor in
maintaining pH of the body fluids.
ACIDIFICATION OF URINE
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PATTERN OF H SECRETION IN PCT, THICK ALH & EARLY
DCT
• Active secretion of hydrogen ions into the renal tubule.
• Tubular reabsorption of bicarbonate ions by combination with hydrogen ions to form
carbonic acid, which dissociates to form carbon dioxide and water;
• Sodium ion reabsorption in exchange for hydrogen ions secreted
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PATTERN OF H+ SECRETION IN LATE DCT & COLLECTING
TUBULE
•
Primary active secretion of hydrogen ions through the luminal membrane of the
intercalated epithelial cells.
•
One bicarbonate ion is absorbed for each hydrogen ion secreted, and a chloride ion is
passively secreted along with the hydrogen ion.
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PHOSPHATE MECHANISM
• In the tubular cells, carbon dioxide combines
with water to form carbonic acid. It
immediately dissociates into H + and HCO3~.
HCO3- from the tubular cell enters the
interstitium.
• Simultaneously Na+ is reabsorbed from renal
tubule under the influence of Aldosterone.
Na+ enters the interstitium and combines with
HCO3~.
• The H+ is secreted into the tubular lumen
from the cell in exchange for Na + .
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PHOSPHATE MECHANISM
• The H+, which is secreted into renal tubules
reacts with phosphate buffer system. It combines
with sodium hydrogen phosphate to form Sodium
dihydrogen phosphate.
• Sodium dihydrogen phosphate is excreted in
urine.
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PHOSPHATE MECHANISM
• The H+, which is added to urine in the form of
Sodium dihydrogen, makes the urine acidic.
• It happens mainly in distal tubule and collecting
duct because of the presence of large quantity of
sodium hydrogen phosphate in these segments.
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PHOSPHATE MECHANISM
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AMMONIA MECHANISM
• This is the most important mechanism by
which kidneys excrete H + and make the
urine acidic.
• In the tubular epithelial cells, ammonia is
formed when the amino acid glutamine is
converted into glutamic acid in the presence
of the enzyme glutaminase.
• Ammonia is also formed by the deamination
of some of the amino acids such as glycine
and alanine.
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AMMONIA MECHANISM
• The ammonia (NH3) formed in tubular cells is
secreted into tubular lumen in exchange for sodium
ion.
• Here, it combines with H+ to form ammonium
(NH4). The tubular cell membrane is not permeable
to ammonium. Therefore, it remains in the lumen
and combines with sodium acetoacetate to form
ammonium acetoacetate.
• Ammonium acetoacetate is excreted through urine.
Thus, H+ is added to urine in the form of ammonium
compounds resulting in Acidification of urine.
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AMMONIA MECHANISM
• This process takes place mostly in the PCT
because glutamine is converted into ammonia in
the cells of this segment.
• Thus, by excreting H+ and conserving HCO3~,
kidneys produce acidic urine and help to maintain
the acid base balance of body fluids.
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NH3 SECRETION
NH3 being lipid
soluble diffuses
across the cell
membrane into ISF
& lumen. In the
lumen H+ + NH3 =
NH4+ remains in
urine.
ACIDIFICATION OF URINE
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NH3 SECRETION
NH3 enters the
tubular lumen not
by filtration but by
synthesis &
secretion in the
Renal cell of
collecting Ducts
and DCT.
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GENERATION OF NEW HCO 3- BY NH3 BUFFER SYSTEM
• Production and secretion of ammonium ion (NH 4+) by proximal tubular cells.
• Glutamine is metabolized in the cell, yielding NH 4+ and bicarbonate. The NH 4+ is
secreted into the lumen by a sodium-NH4+ pump.
• For each glutamine molecule metabolized, two NH 4+ are produced and secreted and
two HCO3– are returned to the blood.
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AMMONIA MECHANISM
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