The kidneys play a key role in maintaining acid-base balance by secreting hydrogen ions into the urine and reabsorbing bicarbonate from filtered blood. There are three main mechanisms: 1) secretion of hydrogen ions via sodium-hydrogen countertransport in the proximal tubule and loop of Henle, 2) reabsorption of filtered bicarbonate by converting it to carbonic acid which enters tubular cells and reforms bicarbonate, and 3) secretion of hydrogen ions directly via proton pumps in collecting duct intercalated cells. Excess hydrogen ions that are not bound to bicarbonate instead react with phosphate and ammonia buffers to form compounds that are excreted in urine, generating new b
2. • The kidneys play a key role in the maintenance of
acid–base balance and to do this they must excrete
acid in the amount equivalent to the production of
nonvolatile acids in the body.
• The kidneys must also filter and reabsorb plasma
bicarbonate, and thus prevent the loss of bicarbonate
in the urine.
3. Kidney regulate extracellular fluid hydrogen ion
concentration through three basic mechanism
1. Secretion of hydrogen ions
2. Reabsorption of filtered bicarbonate ions and
3. Production of new bicarbonate ions
4. • Kidney each day filters 4320meq of bicarbonate.
Because bicarbonate ion must react with a secreted
H+ to form H2CO3 before it can be reabsorbed, 4320
meq of H+ must be secreted each day just to reabsorb
the filtered bicarbonate
• An additional 80meq of H+ must be secreted to rid
the body of non volatile acids produced each day, for
a total of 4400 meq of H+ secreted into the tubular
fluid each day
5. • Concentration of hydrogen ion of body fluid
normally is kept at a very low level.
• If we compare the concentration of H+ with that of
sodium ion concentration, the latter’s concentration is
about 3.5million times greater
• Na+ : 135meq/L
• H+ : 0.00004meq/L (40nEq/L)
6. • Because H+ concentration normally is low, and
because these small numbers are cumbersome, it is
customary to express H+ concentration on a
logarithm scale, using pH units. pH is related to the
actual H+ concentration by the following formula
(H+ concentration is expressed in equivalents per
liter)
• pH= -log [0.00000004]
• pH= 7.4
8. • Bicarbonate acts as a major buffer system in blood
but it has limitations as it can only bind to H+ but not
remove it from the body. To remove H+ from body,
kidney comes into play. Phosphate and ammonia are
other urinary buffers
• In normal health, little excess of H+ is produced in
the body and this is excreted from urine
9. • 80-90% of bicarbonate is reabsorption occurs in
proximal tubule. 10% is reabsorbed in thick
ascending loop of Henle and remainder approx 5% in
distal tubule and collecting duct
10. • Hydrogen ion secretion and HCO3- reabsorption
occur in virtually all parts of the tubules except the
descending and ascending thin limbs of loop of Henle
11. • In proximal tubule and
thick ascending loop of
Henle, hydrogen ion is
secreted by sodium-
hydrogen counter
transport
• There is sodium-
potassium pump in
basolateral membrane
cells which helps in
taking sodium out of cells
to interstitium. So,
sodium will be attracted
from the lumen into the
cells via conc gradient
and H+ counter
transported into tubules
12. • About 95% of the bicarbonate is reabsorbed in this
manner, requiring about 4000mEq of H+ to be
secreted each day by the tubules.
• This mechanism, however, does not establish a very
high H+ concentration in the tubular fluid; the tubular
fluid becomes very acidic only in the collecting
tubules and collecting ducts
13. • After secretion into the
tubule, H+ will react with
filtered HC03- to form
carbonic acid. This is a very
weak base and it difusses
through apical membrane
and enter into tubular cell
and combine with water and
again forms carbonic acid.
• It finally disassociate into
bicarbonate and hydrogen
ions. Bicarbonate formed in
this way gets back into
circulation. For every H+
secreted into tubule equals
amount of HCO3- will be
absorbed into circulation
14. • H+ secretion occurs by yet
another process in intercalated
cells in colleting tubules and
collecting ducts
• Cells here contain proton-
pump mechanism and this
pumps H+ into tubular fluid.
About 15-20% of H+ is
secreted into tubule in this way
• Other 80% of secreted H+ into
tubule will react with
phosphate buffer and form
monosodium
dihydrogenphosphate and will
be excreted in urine.
Meanwhile a new bicarbonate
will be formed and released
into circulation
15. • Here, the tubular epithelium secretes H+ by primary
active transport
• It occurs at the luminal membrane of the tubular cell,
where H+ is transported directly by a specific protein,
a hydrogen-transporting ATPase
• Although the secretion of H+ in the distal tubule and
collecting tubules accounts for only about 5 percent
of the total H+ secreted, this mechanism is important
in forming maximally acidic urine
16. PHOSPHATE BUFFER SYSTEM
• Once all the bicarbonate has been reabsorbed and is
no longer available to bind with hydrogen ions, any
excess H+ can combine with HP04 -- and other
tubular buffers.
• After H+ combines with HP04- to form H2PO4-, it
can be excreted as a sodium salt (NaH2P04), carrying
with it the excess hydrogen
17. • Therefore, whenever a
H+ secreted into tubular
lumen combine with a
buffer other than
bicarbonate, the net
effect is addition of a
new bicarbonate ion to
the blood rather than
merely a replacement of
filtered bicarbonate
18. • Phosphate buffer system carries excess H+ into the
urine and generates new HCO3-
• Therefore, although phosphate is not an important
extracellular fluid buffer, it is much more eefective as
a buffer in the tubular fluid
19. AMMONIA BUFFER SYSTEM
• Ammonium ion is
synthesized from
glutamine. Here, two
NH4+ is secreted and two
HCO3- is reabsorbed.
• For each NH4 excreted, a
new HCO3- is generated
and added to the blood
• In chronic acidosis, the
dominant mechanism by
which acid is eliminated
is excretion of NH4+
20. • Once inside the cell, each molecule of glutamine is
metabolized in a series of reactions to ultimately form
two NH4+ and two HCO3-
• The NH4 is secreted into the tubular lumen by a
counter-transport mechanism in exchange for sodium,
which is reabsorbed.
• The HCO3- is transported across the basolateral
membrane along the reabsorbed Na+, into the
interstitial fluid and is taken up by the peritubular
capillaries