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BUFFERS IN THE BODY
1
PRESENTOR : Dr.KumarMODERATOR :Dr.Prabhavathy
2
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
3
Components of a Buffer
4
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)
9
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.
32
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
34
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++
PHOSPHATE BUFFER SYSTEM
35
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
PHOSPHATE BUFFER SYSTEM
36
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
37
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
38
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+
39
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
40
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+
41
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
42
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
PROTEIN BUFFER SYSTEM
43
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
-
-
-- - - -
----
--
------------
-
--
-
- - - -
+
+++
++
++++
+
++
++ +++
++
++
+++
PROTEIN BUFFER SYSTEM
44
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+
PROTEIN BUFFER SYSTEM
45
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-
PROTEIN BUFFER SYSTEM
46
-
-
-- - - -
----
--
------------
-
--
-
- - - -
+
+++
++
++++
+
++
++ +++
++
++
+++
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+