Acid-Base Balance

RENAL MODULE
SOLA AOUN BAHOUS

Learning Objectives

Describe the major sources of acid gain and loss

Describe the buffering process
Define acidosis and alkalosis

Describe renal handling of acid-base balance with

emphasis on bicarbonate reabsorption and

generation, and on ammonium generation

Outline

Sources of acid gain and loss

The buffering process
Renal handling of acid-base

Outline

Sources of acid gain and loss

The buffering process
Renal handling of acid-base

Sources of Acid Gain and Loss

Sources of Acid Gain and Loss

The major route for H+ gain is the the generation of H+

within the body: two types

Volatile Acids:
15,000 to 20,000 mmol CO2 are generated daily by the
oxidative metabolism
CO2 + H2O
H2CO3
H+ + HCO-3
This reaction is reversed during passage of blood
through the lungs no net gain of H + unless net
retention of CO2 (hypoventilation)
1.

Sources of Acid Gain and Loss

Nonvolatile acids:

2.
a.
b.
c.

Inorganic acids: include: sulfuric acid and phosphoric acid

Organic acids: lactic acid, ketone bodies and others
Ammonium: NH4+

Dissociation of organic acids anions and H+ but

the metabolism of organic anions uses H+ as well
- when diet is high in proteins/ American
diet, there is net production of H+
- in vegetarian diet, there is net production
of HCO-3

Sources of Acid Gain and Loss

NH4+ cannot dissociate in the blood:

NH4+

NH3 + H+ pK = 9.2 very high

The kidneys excrete the 40-80 mmol of H+

generated by the average American diet or excrete

the amount of HCO-3 produced by the vegetarian
diet

Sources of Acid Gain and Loss

The kidneys regulate homeostatically H+ balance

when net retention or elimination of H+ through the

respiratory tract, the GI tract or through the internal
metabolism occur
Sometimes the kidneys generate the H+ imbalance

Outline

Sources of acid gain and loss

The buffering process
Renal handling of acid-base

The Buffering Process

H+ are produced buffered eliminated

EC

CO2-HCO-3
system

IC

phosphates and
proteins

Why the buffering before elimination?

The normal ECF pH is 7.4 which corresponds to H+

of 40 nmol/L

If no buffering occurs between production and

excretion, the net daily H+ production of 40-80 mmol

(millions of nanomoles) will produce huge changes in
pH

Buffering minimizes these changes in H+ but does not

eliminate H+

The Buffering Process

The Buffering Process

pH = 6.1 + log

HCO-

0.03PCO2

Henderson-Hasselbalch equation

Regulation of PCO2 and [HCO-3] achieves regulation

of the pH

Outline

Sources of acid gain and loss

The buffering process
Renal handling of acid-base

Renal Handling of Acid-Base

How the kidneys control H+ balance?
By adjusting the excretion of the filtered and/or

secreted HCO-3
By adding new HCO-3 to the blood flowing through
them

Renal Handling of Acid-Base

Acidosis = high plasma [H+] or low plasma [HCO-3]
Alkalosis = low plasma [H+] or high plasma [HCO-3]
The kidneys compensate for acidosis by adding new

HCO-3 to the blood thereby excreting an acid urine and

alkalinizing the blood
The kidneys respond to alkalosis by excreting large

quantities of HCO-3 in the urine excreting an

alkaline urine and acidifying the blood

Renal Handling of Acid-Base

Bicarbonate excretion:
HCO-3 is filtered, reabsorbed and secreted
Excreted HCO-3 = filtered HCO-3 + secreted HCO-3

reabsorbed HCO-3

Renal Handling of Acid-Base

Bicarbonate filtration and reabsorption:
Filtered HCO-3 /d = GFR x P HCO3
Filtered HCO 3 /d = 180 L/d x 24 mmol/L = 4320
mmol/d
Excretion of this amount of HCO-3 is equivalent to

adding more than 4 L of 1 N acid to the body!

reabsorption is an essential conservation process

Renal Handling of Acid-Base

Bicarbonate reabsorption is an active process

accomplished by H+ secretion
H+ secretion occurs mainly in the proximal tubule,

thick ascending limb of Henles loop and collecting

duct system (type A intercalated cells)
The net result is that, for every H+ secreted into the

lumen, a bicarbonate enters the blood in the

peritubular capillaries

Renal Handling of Acid-Base

Renal Handling of Acid-Base

Specific H+ transporters exist at the luminal

membrane:
* primary active H+-ATPase in all the tubular
segments that secrete H+
* Na+-H+ countertransporter in the proximal
tubule and thick ascending limb of Henles loop
(secondary active transport)

* H+,K+-ATPase in the type A intercalated cells

Renal Handling of Acid-Base

Bicarbonate exits the basolateral membrane

downhill via Cl-/HCO3- countertransporter or

Na+/HCO3- cotransporter depending on the tubular
segment

Renal Handling of Acid-Base

Renal Handling of Acid-Base

How secretion of H+ accomplishes HCO-3 reabsorption

and what happens to the secreted H+?

Renal Handling of Acid-Base

Renal Handling of Acid-Base

The bicarbonate that appears in the peritubular

capillaries is not the same bicarbonate that was filtered

but the overall result is the same
The secreted H+ is not excreted: every H+ secreted in

the lumen that combines with HCO-3 to cause HCO-3

reabsorption does not contribute to the urinary
excretion of H+

Renal Handling of Acid-Base

The proximal tubule reabsorbs ~ 80% of the filtered

bicarbonate

The thick ascending limb reabsorbs 10-15% of the filtered

bicarbonate

The remaining bicarbonate is reabsorbed by the DCT and

collecting duct system

Type-B intercalated cells which are present only in the

CCD achieve bicarbonate secretion (minimal

contribution in humans)

Renal Handling of Acid-Base

Renal Handling of Acid-Base

Addition of new bicarbonate to the blood: renal
excretion of H+:
The kidneys conserve the filtered bicarbonate by
reabsorbing it
The kidneys can compensate for acidosis by adding

new bicarbonate to the blood

Renal Handling of Acid-Base

2 mechanisms for addition of new bicarbonate to the
blood:
Secretion and excretion of H+ by binding of H+ to non

HCO-3 filtered buffers

Catabolism of glutamine to yield NH4+ (ammonium)

which will be excreted in the urine

Renal Handling of Acid-Base

1- H+ secretion and excretion:
Whether bicarbonate is reabsorbed or newly added to

the blood depends on the fate of secreted H+

If secreted H+ binds to filtered HCO-3 HCO-3

reabsorption

If secreted H+ binds to nonbicarbonate buffers

addition of new HCO-3

Renal Handling of Acid-Base

Renal Handling of Acid-Base

The most important non bicarbonate filtered buffer is

phosphate

When the kidneys add new bicarbonate to the blood,

they excrete H+ (buffered) in the urine

Filtered H+ does not contribute a lot to excreted H+

because [H+] at pH 7.4 is < 10-7 M < 0.1 mmol H+

filtered/d

Renal Handling of Acid-Base

Is there a threshold for H+ secretion?

There is a minimum urinary pH that can be achieved

(~ 4.4) because H+ transporters are inhibited at low

pH i.e. there is limit to the correction of acidosis

Renal Handling of Acid-Base

Phosphate and organic acids as buffers:
HPO4-- + H+

H2PO4

pK = 6.8

At physiological pH we have more HPO4-- (dibasic) for

buffering than H2PO4 (weaker buffer) at the

minimal urinary pH almost all HPO4-- is converted to
H2PO4

Renal Handling of Acid-Base

Phosphate is bound in part to plasma proteins

[phosphate] in the filtrate is 1 mmol/L

Filtered phosphate = 180 mmol/d
Filtered HPO4-- = 80% x 180 = 144 mmol/d
75% of filtered phosphate is reabsorbed the

available phosphate for buffering = 0.25 x 144 = 36

mmol/d

Renal Handling of Acid-Base

What determines the fate of H+?

1- pK of each buffer-pair reaction
2- the concentration of each buffer
[HCO-3] is much higher compared to other buffers

the contribution of these other buffers occurs when a

big amount of HCO-3 has been reabsorbed

Renal Handling of Acid-Base

Bicarbonate reabsorption prevents the development of

acidosis caused by bicarbonate loss

Addition of new bicarbonate to the blood compensates

for acidosis

Renal Handling of Acid-Base

Renal Handling of Acid-Base

2- Glutamine catabolism and NH4+ excretion:

The proximal tubule is the main site for ammonium
production
1 glutamine 2 NH4+ + 2 HCO-3
Most of the NH4+ formed by the proximal tubule is

excreted and the actual percentage excreted is under

physiological control

Renal Handling of Acid-Base