Acid Base BaLance

Inputs and Outputs of Acid

 Removing Acid or Base
• Buffers
– Blood seconds
– Intracellular minutes
• Lung hours
– “compensated state”
• Kidneys days

• Net acid excretion counts NH4, Titratable Acid, HCO3-

– Titratable (weak) acids include lactic acid, ketone bodies, etc.
– Strong acids are secreted as their Na salts (eg, Na2SO4)
 Body deals with pH changes by 3 mechanisms

CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3

NH3 + H+ ⇌ NH4+
HPO42- + H+ ⇌ HPO4-

Buffers 1st defense, immediate response

Ventilation 2nd line of defense, can
handle ~ 75% of most pH
disturbances
Renal regulation of H+ & HCO3- final
defense, slow but very effective
Acid–Base Balance
• Normal blood pH ?
– ↑ pH = Alkalosis

– ↓ pH = Acidosis

• [H+] is the same in ECF and ICF

– Kidneys have K+/H+ antiport

– Importance of hyperkalemia and

hypokalemia

• CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-

– pH can be altered by respiration

• Renal Compensation
– H+ excretion, e.g., NH3 + H+ ⇌ NH4+

– HPO42- + H+ ⇌ HPO4-
 Lung Mechanisms
• CO2 is an acid and gets blown out by
respiration.
– So when you sprint, you develop lactic
acidosis. This is metabolic acidosis. To get
rid of the acid, you hyperventilate and
breathe faster.
 Urinary Buffers

• Nephron cannot produce urine with pH < 4.5

• Excretes more H+ by buffering H+s with HPO4-2
or NH3 before excretion
• Phosphate enters tubule during filtration
• Ammonia produced in tubule by deaminating
amino acids
• Buffering reactions
– HPO4-2 + H+  H2PO4-
– NH3 + H+  NH4+ (ammonium ion)
 Renal Acid-Base Regulation

• Kidneys help regulate blood pH by excreting

H+ &/or reabsorbing HC03-
• Most H+ secretion occurs across walls of PCT
in exchange for Na+ (Na+/H+ antiporter)
• Normal urine is slightly acidic (pH = 5-7)
because kidneys reabsorb almost all HC03- &
excrete H+
 Kidney Mechanisms
Mainly by HCO3-

H2O + CO2 CA H2CO3  HCO3- + H+

 Kidney: HCO3-

• Regulation
– Proximal tubule: follows Na+ (understand why)
– Na/H antiport. Whenever one H+ exits, a tubular HCO3- is used
up to neutralize it. Also, to regenerate that H+, a HCO3 is made,
which is transported to the blood.
– Systemic Acidosis (in PCT, Henle, CD)
 Nitrogen Removal (NH3 or NH4+)
The mechanisms are complicated

Know that H+ acidifies & traps NH3 in the lumen

(as NH4+)
 Collecting Tubules
• Two important cell types are found here
– Intercalated cells
• Cuboidal cells with microvilli
• Function in maintaining the acid-base balance of the
body
– Principal cells
• Cuboidal cells without microvilli
• Help maintain the body’s water and salt balance
 Reabsorption of HCO3- in PCT
• When urine is acidic, HCO3- combines with H+ to
form H2C03 (catalyzed by CA on apical membrane
of PCT cells)
• H2C03 dissociates into C02 + H2O
• C02 diffuses into PCT cell & forms H2C03
(catalyzed by CA)
• H2C03 splits into HCO3- & H+ ; HCO3- diffuses into
blood
 Reabsorption of HCO3- in PCT

• Indirect because apical membranes of PCT cells are

impermeable to HCO3-
• When urine is acidic, bicarbonate combines with H+
to form carbonic acid
• Carbonic acid in filtrate is converted to carbon
dioxide and water in a reaction catalyzed by carbonic
anhydrase (CA)
– located in apical cell membrane of PCT in contact with
filtrate
Hydrogen Secretion—through proton pump:

accounts for only about 5 percent of the total

hydrogen ion secreted
Important in forming a maximally acidic urine.

Hydrogen ion concentration can be increased

as much as 900-fold in the collecting tubules.

Decreases the pH of the tubular fluid to

about 4.5, which is the lower limit of pH that
can be achieved in normal kidneys.
Hydrogen Ion Secretion
Hydrogen Secretion and Bicarbonate
Reabsorption.

(1)Hydrogen secretion through secondary Active

Transport.

Mainly at the proximal tubules, loop of Henle, and

early distal tubule ;

More than 90 percent of the bicarbonate is

reabsorbed (passively ) in this manner .
 Reabsorption of HCO3- in PCT
• Is indirect because apical membranes of PCT
cells are impermeable to HCO3-
Glutamine Metabolism in the PCT
For each molecule of glutamine
metabolized in the proximal tubules, two
NH4+ ions are secreted into the urine and
two HCO3- ions are reabsorbed into the
blood.

The HCO3- generated by this process

constitutes new bicarbonate.
 Buffering of hydrogen ion secretion by
ammonia (NH3) in the collecting tubule.
Renal ammonium-ammonia buffer system is
subject to physiological control.

An increase in extracellular fluid hydrogen ion

concentration stimulates renal glutamine
metabolism and, therefore, increase the
formation of NH4+ and new bicarbonate to be
used in hydrogen ion buffering;

a decrease in hydrogen ion concentration has

the opposite effect.
with chronic acidosis, the dominant mechanism by
which acid is eliminated of NH4+.
This also provides the most important mechanism for
generating new bicarbonate during chronic acidosis.
Primary Active Transport
Secondary Active Transport
4. Excretion of Excess Hydrogen Ions and
Generation of New Bicarbonate by the
Ammonia Buffer System
 Buffering of hydrogen ion secretion by
ammonia (NH3) in the collecting tubule.
For each molecule of glutamine metabolized in the
proximal tubules, two NH4+ ions are secreted into the
urine and two HCO3- ions are reabsorbed into the
blood.

The HCO3- generated by this process constitutes new

bicarbonate.
Production and secretion of ammonium
ion (NH4+) by proximal tubular cells.
Acid-Base Disturbances/Compensation
Arterial pH

pH < 7.35 OR pH > 7.45

Acidosis Alkalosis

[HCO3–] < 24 mM OR PCO > 40 mm Hg [HCO3–] > 24 mM OR PCO < 40 mm Hg

2 2

Metabolic acidosis Respiratory acidosis Metabolic alkalosis Respiratory alkalosis

Respiratory Renal Respiratory Renal

compensation compensation compensation compensation

PCO < 40 mm Hg [HCO3–] > 24 mM PCO > 40 mm Hg [HCO3–] < 24 mM

2 2
 Metabolic Alkalosis
– Cause: decreased H+ independent of CO2
– Compensation: respiratory and renal (unless renal
problem)
– Respiratory compensation
• Decrease ventilation  increase CO2
– Renal compensation
• Decrease H+ secretion
• Decrease HCO3- reabsorption
• Decrease synthesis of new bicarbonate
 Response to Decrease in pH

Copyright © 2008 Pearson

Education, Inc., publishing
as Benjamin Cummings.