RENAL CLEARANCE

H+/HCO3

-BALANCE

ACIDOSIS AND ALKALOSIS

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RENAL CLEARANCE:

The renal clearance of any substance

is the volume of plasma from which

that substance is completely removed

or “cleared” by the kidneys per unit

time.

The units are always in

volume of plasma per unit of time.

The basic clearance formula

for any substance S is:

Clearance of S = Mass of S excreted per unit

time

Plasma concentration of S

Because the mass of S excreted per unit

time is equal to the urine concentration of

S multiplied by the urine volume during that

time,

the formula for the clearance of S

becomes:

Where, C = Clearance of S

U = Urine concentration of S

V = Urine volume per unit time

P = Plasma concentration of S

CS = US V

PS

Some examples:

1)Glucose

The clearance of glucose is normally zero

because all of the glucose that is filtered from

the plasma into the glomeruli is reabsorbed

back into the blood.

2)Inulin

It is freely filtered but neither reabsorbed nor

secreted. The amount of inulin entering the

nephrons from the plasma would be equal to

the amount of inulin excreted in the urine.

The filtered load of a substance is the

glomerular filtration rate (GFR) multiplied by the

plasma concentration of the substance.

(GFR )(Pin ) = (Uin )(V )

On rearranging,

GFR = Uin V

Pin

In other words, the GFR of a person is equal to

the clearance of inulin ( UV / P ).

H+/HCO3

-BALANCE

The kidneys eliminate or replenish H+ from the

body by altering plasma bicarbonate

concentration.

The excretion of HCO3- in the urine increases the

plasma hydrogen ion concentration just as if a

hydrogen ion had been added to the plasma.

Similarly, the addition of HCO3- to the plasma

decreases the plasma hydrogen ion

concentration just as if a hydrogen ion had been

removed from the plasma.

carbonic

anhydrase

CO2 + H2O ⇌ H2CO3 ⇌HCO3- + H+

Thus, when the plasma hydrogen ion concentration

decreases (alkalosis) for whatever reason, the kidneys’

homeostatic response is to excrete large quantities of

HCO3- .

This increases plasma hydrogen ion concentration

toward normal. In contrast, when plasma hydrogen

ion concentration increases (acidosis), the kidneys do

not excrete HCO3- in the urine.

Rather, kidney’s tubular cells produce new HCO3-

and add it to the plasma. This decreases the plasma

hydrogen ion concentration toward normal.

BICARBONATE

REABSORPTION &

H+ SECRETIONThe process of bicarbonate reabsorption occur

predominantly in the proximal tubule (about 90%). The

rest occur in the thick ascending limb and in the

collecting tubule.

The primary step in proximal hydrogen secretion is the

secretion of H+ by the Na+ - H+ antiporter in the

luminal membrane. Hydrogen ions are generated by

the intracellular breakdown of H20 to OH- and H+.

Hydrogen ions secreted combine with filtered HCO3-

ions to form carbonic acid and then CO2 + H2O, which

are then passively reabsorbed.

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Similar processes occur in the thick ascending loop of

Henle and intercalating cells of the collecting duct. In

contrast to the proximal tubule, hydrogen ion secretion

in the collecting tubule is mediated by a H+ ATPase

pump in the luminal membrane and a Cl-HCO3-

exchanger in the basolateral membrane as shown in

the diagram above. The H+ ATPase pump is influenced

by aldosterone, which stimulates increased H+

secretion.

Proximal reabsorption of bicarbonate can be affected

by many factors, in particular, potassium balance,

volume status and renin/angiotensin levels.

Therefore these factors can have very significant

effects on acid base balance. Their specific effects will

be discussed later.

ACIDOSIS AND ALKALOSIS

The normal pH value for the body fluids is between pH 7.35 and 7.45. When the pH value of body fluids is below 7.35, the condition is called acidosis, and when the pH is above 7.45, it is called alkalosis.

Rapid elimination of acidic products of metabolism results in alkalosis, and the failure to eliminate acidic products of metabolism results in acidosis.

Although buffers in the body fluids help resist changes in the pH of body fluids, the respiratory system and the kidneys regulate the pH of the body fluids. Malfunctions of either the respiratory system or the kidneys can result in acidosis or alkalosis

The major effect of acidosis is depression of the

central nervous system. When the pH of the blood

falls below 7.35, the central nervous system

malfunctions, and the individual becomes disoriented

and possibly comatose as the condition worsens.

A major effect of alkalosis is hyperexcitability of the

nervous system. Peripheral nerves are affected first,

resulting in spontaneous nervous stimulation of

muscles. Spasms and tetanic contractions and

possibly extreme nervousness or convulsions result.

Severe alkalosis can cause death as a result of

tetany of the respiratory muscles.

Acidosis and alkalosis are categorized by the cause

of the condition. Respiratory acidosis or respiratory

alkalosis results from abnormalities of the respiratory

system. Metabolic acidosis or metabolic alkalosis

results from all causes other than abnormal

respiratory functions.

Respiratory acidosis is due to retention of carbon

dioxide,

and respiratory alkalosis is due to excessive

elimination of

carbon dioxide.

All other causes of acidosis or alkalosis are termed

metabolic and reflect gain or loss, respectively, of

H+ from a source other than carbon dioxide.

Inadequate ventilation of the lungs causes

respiratory acidosis. The rate at which carbon

dioxide is eliminated from the body fluids

through the lungs falls. This increases the

concentration of carbon dioxide in the body

fluids.

As carbon dioxide levels increase excess

carbon dioxide reacts with water to form

carbonic acid. The carbonic acid dissociates to

form hydrogen ions and bicarbonate ions. The

increase in hydrogen ion concentration causes

the pH of the body fluids to decrease.

Respiratory alkalosis results from

hyperventilation of the lungs. This increases

the rate at which carbon dioxide is eliminated

from the body fluids and results in a decrease

in the concentration of carbon dioxide in the

body fluids.

As carbon dioxide levels decrease, hydrogen

ions react with bicarbonate ions to form

carbonic acid. The carbonic acid dissociates to

form water and carbon dioxide. The resulting

decrease in the concentration of hydrogen ions

cause the pH of the body fluids to increase.

Metabolic acidosis results from all conditions that

decrease the pH of the body fluids below 7.35, with

the exception of conditions resulting from altered

function of the respiratory system. As hydrogen ions

accumulate in the body fluids, buffers first resist a

decline in pH. If the buffers cannot compensate for

the increase in hydrogen ions, the respiratory center

helps regulate the body fluid pH.

The reduced pH stimulates the respiratory center,

which causes hyperventilation. During

hyperventilation, carbon dioxide is eliminated at a

greater rate. The elimination of carbon dioxide also

eliminates excess hydrogen ions and helps maintain

the pH of the body fluids within a normal range.

If metabolic acidosis persists for many hours

and if the kidneys are functional, the kidneys

can also help compensate for metabolic

acidosis. They begin to secrete hydrogen ions

at a greater rate and increase the rate of

bicarbonate ion reabsorption. Symptoms of

metabolic acidosis appear if the respiratory

and renal systems are not able to maintain the

pH of the body fluids within its normal range

Metabolic alkalosis results from all conditions that

increase the pH of the body fluids above 7.45, with the

exception of conditions resulting from altered function

of the respiratory system.

As hydrogen ions decrease in the body fluids, buffers

first resist an increase in pH. If the buffers cannot

compensate for the decrease in hydrogen ions, the

respiratory center helps regulate the body fluid pH.

The increased pH inhibits respiration. Reduced

respiration allows carbon dioxide to accumulate in the

body fluids. Carbon dioxide reacts with water to

produce carbonic acid. If metabolic alkalosis persists

for several hours, and if the kidneys are functional, the

kidneys reduce the rate of hydrogen ion secretion to

help reverse alkalosis.

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