Buffers in the body

BUFFERS IN THE BODY

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PRESENTOR : Dr.KumarMODERATOR :Dr.Prabhavathy

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Buffers resist changes in pH from the addition of acid

orbase

in the body absorb H3O+ or OH from foods and cellular processes to maintain pH

are important in the proper functioning of cells and blood

in blood maintain a pH close to 7.4; a change in the pH of the blood affects the uptake of oxygen and cellular processes

Buffers (continued)

When an acid or base

is added to water, the pH

changes drastically

to a buffer solution, the pH does not change very much; pH is maintained

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Components of a Buffer

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The components of a buffer solutionare acid–base conjugate pairscan be a weak acid and a salt of its

conjugate basetypically have equal concentrations of

the weak acid and its saltcan also be a weak base and a salt of

its conjugate acid

The Major Body Buffer Systems

Body Buffer system

-Hydrogen ion Homeostasis-Control system -Control CO2 (PCO2) By lungs -Control HCO3- By Kidney and Erythrocytes

Body Buffer system• Hydrogen Ion Homeostasis

About 50 to100 m mol of hydrogen ions

are released from cells into extracellular fluid each day

• Hydrogen ion concentration [H+] is maintained between about 35 and 45 nano mol\L. (40nmol/L=pH 7.4)

• Control of hydrogen ion balance depends on the secretion of H+ from the body, mainly into the urine therefore Renal impairment causes acidosis

-Aerobic metabolism of the carbon skeletons of organic compounds converts from hydrogen, carbon and oxygen to water and carbon dioxide (CO2)

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C C C C C C

H H H H H H

HHHHHH

CO2 is essential compound of extracellular buffering system

-Control of CO2 depends on normal lung function.

Buffering

Is a process by which a strong acid (or base) is replaced by a weaker one, with a consequent reduction in the number of free hydrogen ions and therefore the change in PH

HCl + NaHCO3 = H2CO3 + NaCl

Strong acid buffer weak acid neutral salt

PH is a measure of hydrogen ion activity

Log 100 =log 102=2 Log 107=7 If [H+] is 10-7 (0.000 0001)Then log [H+] =-7 The Henderson –hasselbalch equation PH=PK+log [base] /[acid]

The bicarbonate pair is an important biological buffer example;

H2CO3 HCO3- + H+

Acid baseThe base is bicarbonate (HCO3

-) and the carbonic acid (H2CO3) .

-It is not possible to measure the latter directly

however it is in equilibrium with dissolved CO2 of which the partial pressure (PCO2) can be estimated.

The conc. of H2CO3 is derived by multiplying this measured value by the solubility co efficient (s) for CO2 therefore

PH =PK-log [HCO3-]/PCO2 XS (0.03 )

Hydrogen ion Homeostasis PH is relatively tightly controlled in blood by

the following mechanisms

1-Hydrogen ions can be incorporated in water

H+ + HCO3- H2CO3 CO2 + H2O

This is normal mechanism during oxidative phos phorylation. H+ is inactivated by combining with the HCO3 only if the reaction is driven to the right by the removal of CO2.

By this would cause bicarbonate depletion

H+ can be lost from the body only through the kidney and the intestine .This mechanism is coupled with the generation of bicarbonate ion (HCO3

-) In the kidney this is the method which

secretion of excess H+ ensures regeneration of buffering capacity

Control system CO2 and H+ are potentially toxic products of

aerobic and anaerobic metabolism most CO2 is lost through the lungs but

some is converted to bicarbonateThus contributing important extracellular

buffering capacity Bicarbonate system is the most important

buffer in the body because has high capacity.

The control of CO2 (PCO2) by the Respiratory center and lungs

The partial pressure of CO2 in plasma is normally about 5.3 kpa (40 mmHg) and depend on the balance between the rate of production by metabolism and the loss through the pulmonary .

the rate of respiration, and then therefore the

rate of CO2 elemination is controlled by

chemoreceptor in the respiratory centre in the

medulla of the brain.

The receptors respond to changes in the

[CO2]or[H+] of plasma or of the cerebrospinal

fluid .

1. the PCO2 rises much above 40 mm of Hg

2. the PH falls, the rate of respiration

increases .

Normal lungs have a very large reserve capacity for CO2

elimination

The normal respiratory centre and lungs can control CO2

conc. Within norrow limits by responding to changes in the

[H+] and therefore compensate for changes in acid-base

disturbances .

diseases of the lungs, or abnormalities of respiratory

control, primarily affect the PCO2

The Control of Bicarbonate by-The Kidneys and Erythrocytes

The renal tubular cells and erythrocytes generate bicarbonate, the buffer base in the bicarbonate system from CO2 under

physiological conditions.

The erythrocyte mechanism makes fine adjustments to the plasma bicarbonate conc. In response to changes in PCO2 in lungs and tissues.

The kidneys play the major role in maintaining the circulating bicarbonate conc. And in elimination H+ from the body.

The carbonate dehydratase system

Bicarbonate is produced following the dissociation of carbonic acid formed from CO2and H2O.

This is catalyzed by carbonate dehydratase (CD) present in high conc. in erythrocytes and renal tubular cells.

CO2 + H2O H2CO3 H+ + HCO3

-

Carbonate dehydratase

In addition to content erythrocytes and renal tubular cell to CD they also have means

of removing one of the products, H+ thus both reactions continues to the right and HCO3- is formed.

one of the reactants, water, is freely available and one of the products, H+ is removed.

HCO3- generation is therefore accelerated if the

conc.of 1. CO2 rises2. HCO3

- falls.3. H+ falls because it is either buffered by

erythrocytes or excreted from the body by renal tubular cells.

Therefore an increase of intracellular P CO2 or decrease in intracellular [HCO3

-] in the erythrocytes and renal tubular cells maintain the extracellular bicarbonate conc. by accelerating the production of HCO3

-.This minimizes changes in the ratio of [HCO3

-] to PCO2 and therefore change in PH.

In normal subject, at a plasma ;

1. PCO2 of 40mm of hg (a CO2 of about 1.2 mmol\L)

2. Erythrocytes and renal tubular cells keep the extracellular bicarbonate at about 25 mmol\L

3. The extracellular ratio of [HCO3-] to [CO2]

(both in mmol\L) is just over 20:1.

Bicarbonate Generation by the ErythrocytesErythrocytes produce little CO2 as they lack aerobic pathway

Plasma CO2 diffuses along a concentration gradient into

erythrocytes, where carbonate dehydratase catalyses its

reaction with water to from carbonic acid (H2CO3) which then

dissociates

Much of the H+ is buffered by hemoglobin and the HCO3-

diffuses out into the extracellular fluid along a conc.

Gradient

CARBON DIOXIDE DIFFUSION

28 CO2

Red Blood CellSystemic Circulation

H2O

H+ HCO3-

carbonicanhydrase

Plasma

CO2 CO2CO2 CO2 CO2 CO2

CO2

Click for Carbon Dioxide diffusion+ +

Tissues

H+

Cl-

HbH+ is buffered by

Hemoglobin

The kidneysTwo renal mechanism control [HCO3

-]in the extracellular fluid:

Bicarbonate reclamation (reabsorption)

The CO2 driving in renal tubular cells is derived from filtered bicarbonate, after action of the carbonate dehydratase.

There is no correct to an acidosis but can maintain a steady state.

Normal urine is nearly HCO3- free. An amount

equivalent to that filtered by the glomeruli is returned to the body by the tubular cells.

The luminal surface of renal tubular cells are impermeable to HCO3

- .

Thus, HCO3- can only be returned to the body

if first converted to CO2 in the tubular Lumina, and an equivalent amount of CO2 is converted to HCO3

- with in tubular cells.

The luminal surface of renal tubular cells are

impermeable to HCO3- , Thus, HCO3

- can only

be returned to the body if first converted to

CO2 in the tubular Lumina, and an equivalent

amount of CO2 is converted to HCO3- with in

tubular cells.

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Capillary Distal Tubule Cells

Tubular Urine

NH3

Na+ Cl-+H2CO3HCO3

- +NaCl

NaHCO3

Click Mouse to Start Animation

NaHCO3

NH3Cl-

H+

NH4ClClick Mouse to See Animation Again

Notice theH+ - Na+

exchange to maintain electrical neutrality

Bicarbonate generation

A very important mechanism for correcting acidosis, in which the levels of CO2 or [HCO3

-] affecting the carbonate dehydratase reaction in tubular cells reflect those in the extracellular fluid, there is a net loss of H+

PHOSPHATE BUFFER SYSTEM

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1) Phosphate buffer system

Na2HPO4 + H+ NaH2PO4 +

Na+ Most important in the intracellular system

Alternately switches Na+ with H+

H+ Na2HPO4+

NaH2PO4Click to animate

Na++


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Na2HPO4 + H+ NaH2PO4 +

Na+

Phosphates are more abundant within the cell and are rivaled as a buffer in the ICF by even more abundant protein

Na2HPO4

Na2HPO4

Na2HPO4


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Regulates pH within the cells and the urinePhosphate concentrations are higher intracellularly and within the kidney tubules

Too low of aconcentration inextracellular fluidto have muchimportance as anECF buffer system

HPO4-2

PROTEIN BUFFER SYSTEM

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Behaves as a buffer in both plasma and cells

Hemoglobin is by far the most important protein buffer.

Most important intracellular buffer (ICF)The most plentiful buffer of the bodyProteins are excellent buffers because they

contain both acid and base groups that can give up or take up H+

Proteins are extremely abundant in the cellThe more limited number of proteins in the

plasma reinforce the bicarbonate system in the ECF

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Hemoglobin buffers H+ from metabolically produced CO2 in the plasma only

As hemoglobin releases O2 it gains a great affinity for H+

HbO2

O2 O2

O2

H+

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H+ generated at the tissue level from the dissociation of H2CO3 produced by the addition of CO2

Bound H+ to Hb (Hemoglobin) does not contribute to the acidity of blood

HbO2

O2 O2

O2

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As H+Hb picks up O2 from the lungs the Hb which has a higher affinity for O2 releases H+ and picks up O2

Liberated H+ from H2O combines with HCO3

-

HCO3- H2CO3 CO2

(exhaled)Hb

O2

O2 O2

H+

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Venous blood is only slightly more acidic than arterial blood because of the tremendous buffering capacity of Hb

Even in spite of the large volume of H+ generating CO2 carried in venous blood

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Proteins can act as a buffer for both acids and bases

Protein buffer system works instantaneously making

it the most powerful in the body

75% of the body’s buffer capacity is controlled by

protein

Bicarbonate and phosphate buffer systems require

several hours to be effective


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Proteins are very large, complex molecules in comparison to the size and complexities of acids or bases

Proteins are surrounded by a multitude of negative charges on the outside and numerous positive charges in the crevices of the molecule

-

-

-- - - -

----

--

------------

-

--

-

- - - -

+

+++

++

++++

+

++

++ +++

++

++

+++


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H+ ions are attracted to and held from chemical interaction by the negative charges

-

-

-- - - -

----

--

------------

-

--

-

- - - -

+

+++

++

++++

+

++

++ +++

++

++

+++

H+

H+

H+

H+ H+ H+ H+ H+ H+ H+

H+

H+

H+

H+

H+H+H+H+H+H+H+


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OH- ions which are the basis of alkalosis are attracted by the positive charges in the crevices of the protein

-

-

-- - - -

----

--

------------

-

--

-

- - - -

+

+++

++

++++

+

++

++ +++

++

++

+++

OH-

OH-

OH-

OH-

OH-OH-

OH-

OH-

OH-OH-

OH-

OH-


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-

-

-- - - -

----

--

------------

-

--

-

- - - -

+

+++

++

++++

+

++

++ +++

++

++

+++

OH-

OH-

OH-

OH-

OH-OH-

OH-

OH-

OH-OH-

OH-

OH-H+

H+

H+

H+ H+ H+ H+ H+ H+ H+

H+

H+

H+

H+

H+H+H+H+H+H+H+

Buffers in the body

Health & Medicine

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