Download Water and Buffers, Acid-Base balance Easy reviewer and more Lecture notes Biochemistry in PDF only on Docsity!
I. OBJECTIVES
- To be able to differentiate the water content among
individuals based on age, sex, and weight
- To be able to apply the properties of water and its uses in
our daily life
- To be able to recognize the role of water and its
biochemical properties
- To be able to determine acids, bases, and buffers in
everyday living
- To be able to apply the Henderson-Hasselbach Equation
- To be able to familiarize self with cases concerning water
balance and basic acid-base problems
II. WATER
● Functions:
® Predominant chemical component of a living organism
® Essential part of body cells and fluids
® Matrix of many living reactions
® Medium for movement in intra and extracellular processes
® Transports compounds in the blood
® Regulates temperature
® Acts as a cushion
● Properties:
® Universal solvent
® High surface tension
® Liquid at room temperature
§ High boiling point
§ High freezing point
§ High latent heat of vaporization
Long Exam # 1 Trans #
Figure 1. Water molecule.
A. BIOCHEMISTRY OF WATER
● 3 atoms: 2 Hydrogen, 1 Oxygen
● Bent molecule: 105°
● Dipolar – has both positive and negative ends
→ High tendency to form hydrogen bonds
→ Simultaneously an H donor and H acceptor
→ Responsible for the solvent property
→ Reactant or product in many metabolic processes
● Hydrogen bonding in water:
→ Allows water to dissolve many organic biomolecules
with functional groups that can participate in binding:
§ Oxygen atoms of aldehydes
§ Ketones
§ Amides
§ Alcohol and amines (H donor and acceptor)
Figure 2. Hydrogen bonding in water.
● Covalent bond with separation of charge = polar bond
between
H and O
→ Shared H electrons are more attracted to O (more
electronegative), giving O a partial negative charge
→ Partial negative on O is twice the strength of one H
OUTLINE
I. Objectives
II. Water
A. Biochemistry of Water
B. Water as a Solvent
C. Water as a Thermal Regulator
D. Distribution of Water in the Body
III. Osmolality
A. Total Osmolality
B. Osmotic Force
IV. pH A. Acid
B. Base
C. Strong and Weak Acids and
Bases
D. Henderson-Hasselbach Equation
V. Buffers
A. Buffer Capacity
B. Acid-Base Buffer Systems
C. Buffers in the Body
D. Acid-Base Balance
E. Acid-Base Disorders
● Both H and O molecules form hydrogen bonds with other
H 2 O molecules
→ O binds with 2 H so each water molecule is H bonded to
four close water molecules
B. WATER AS A SOLVENT
Dissolution occurs because water form bonds and
electrostatic interactions
Hydrogen bonds:
Strong enough to dissolve polar molecules in
water to separate charges
Weak enough to allow movement of water and
solutes
® Strength between 2 water molecules = 4kcal
® H bond between molecules last for only 10
picoseconds, each water molecule in a hydration
shell stays for only 2.4 nanoseconds
® Coulomb’s law: The strength of interaction
between oppositely charged particles is
inversely proportional to the dielectric
constant of the surrounding medium.
Applying this law to water:
a strong dipole has a high dielectric
constant causing low dielectric charge
to surrounding medium H 2
O can then
dissolve large quantities of charged
compounds
*Dielectric constant is the ratio of the
capacitance of a capacitor with the given
material as dielectric, to the capacitance
of the same capacitor with vacuum as the
dielectric (Collins dictionary)
C. WATER AS A THERMAL
REGULATOR
Water’s structure makes it resistant to temperature
change
® High heat of fusion - large drop of temperature is
needed to convert liquid water to solid ice
® High thermal conductivity - facilitates dissipation of
heat
® High heat capacity and heat of vaporization -
gives the cooling effect felt when water
evaporates from skin
D. DISTRIBUTION OF WATER IN THE
BODY
- Total amount of body water: CONSTANT
- Tissue concentration: VARIES
- Water comprises 45-80% of body • Factors that
affect Total Body Water (TBW):
® age (infant > adult)
® sex (male > female)
® weight (thin > average)
® amount of fat (people with less fat > more fat)
Table 1. Comparison of TBW among infants, male and
female adults in relation to their body size
Infant Male
Adult
Female
Adult
Thin 80 65 60
Average 70 60 55
Obese 65 55 45
Computing for Total Body Water
Figure 3. Total body water distribution in an
individual.
Note: In computing, weight must be in kilograms and
fluids in liters. Memorize the formula by heart.
® Fluctuation is <1% of body weight per day
® Intake: 2000 mL
§ goes straight to the extracellular fluid
compartment, will equilibrate with intra
§ water moves from one area to another
depending on osmolality or solutes present
® Output: 2000 mL
§ majority goes to urine output
§ insensible water losses (other ways of
water excretion) such as: o
pulmonary losses - respiration o
sweating
o stool
® Movement between ICF and ECF is equal
® Effects of addition of the following fluids on
cells
§ Hypertonic NaCl o Intracellular
K
will move out to ECF, making
the cell shrink
§ Water
o Extracellular Na
will move
into the intracellular fluid, then
making the cell swell
§ Isotonic saline
o Equal movement o ECF
increases in volume before
going back to normal
Figure 4. Corresponding effects of different fluids on the cell.
III. pH
- pH is the concentration of H
ions in a solution
- pH of pure water = 7
- can be computed by:
- dissociation of water
® H
2
O → H
and OH
extent: 0.0000001M or 10
mol/ L
- Dissociation constant of H 2
O (K
d
or K eq
® relationship between [H+], [OH-] and [H 2
O] at
equilibrium as shown below
is constant at 55.5M since water dissociates at
a small extent when K d
of water is multiplied by
55.5M (constant), it gives the quantity of the ion
product of water
Kw= [H
][OH
]= 1x
and OH
neutral
- Acidic solution pH= <7; higher [H
] and lower [OH
] than pure water
Basic solution pH= >7; lower [H+] and higher [OH
]
than pure water
A. ACID
- Hydrogen donor
- Bronsted Lowry definition
® Proton/ H
donor
® Sour
® Litmus paper: blue to red
® electron pair acceptor; forming covalent bond
® compounds forming H+ from H 2
O dissociation
B. BASE
- Hydrogen acceptor
- Bronsted Lowry definition
® Proton/ H+ acceptor
® Bitter, slippery, soapy
® Litmus paper: red to blue
® electron pair donor
® compounds forming OH- from H 2
O dissociation
C. STRONG AND WEAK ACIDS AND BASES
- Strong acids and bases completely dissociate while
weak acids and bases do not completely dissociate
- Equilibrium constant for weak acid dissociation
® Ability of acid to donate H
ion to a solution K a
® K
a
= [H
+
][A
-
]/ [HA]
- Weak or strong – dependent on the degree of
dissociation into H
and a base
® Metabolically important acids are weak acids
D. HENDERSON-HASSELBALCH
EQUATION
IV. BUFFERS
- Consist of a weak acid and its conjugate base or a
weak base and a conjugate acid
- An aqueous solution that can resist changes in pH
when H
or OH
is added to the buffer
Table 6. Normal Body pH Range.
pH of blood 7.36-7.
or
pH of intracellular fluid 6.9 – 7.
or
pH of extracellular fluid (at
this range, metabolic
functions of the liver, beating
of the heart, and conduct of
neural impulses is still
maintained)
*optimum values
A. BUFFER CAPACITY
- It is defined as the equivalents of (H
) or (OH
required to change 1L of buffer by 1.0 pH unit
- Measured as the effectiveness of a solution to resist
pH changes
- Two factors determine its effectiveness: 1) pKa
relative to the pH of the solution, and 2) concentration
- A buffer has its greatest buffering capacity in the pH
range near its pKa, at +/- 1.0 pH unit on either side
- As the pH of a buffered solution changes from the
pKa to one pH unit below the pKa, the ratio of [A
]
to [HA] changes from 1:1 to 1:10. Until CO 2 is
expired or ions in urine are formed, body fluids
should buffer these changes.
B. ACID – BASE BUFFER SYSTEMS
- Conjugate acid-base pairs that bind or release H
when an acid or base is added to the body so that the
change in pH is minimized
st
line of immediate defense against pH
changes.
- Buffering in ECF: occurs rapidly in minutes
Bicarbonate-Carbonic Acid Buffer System in ECF is the
major buffer system of the body.
Other important buffer systems in the body are:
- Hemoglobin buffer system in RBC
- Phosphate buffer in all cell types
- Protein-buffer system of cells and plasma
C. BUFFERS IN THE BODY
1. Bicarbonate-Carbonic Acid Buffer System in ECF - The major source of metabolic acid in the body is the
gas CO 2
, produced principally from fuel oxidation in
the TCA cycle.
- In normal metabolic conditions, 13 moles of CO 2
are
generated per day.
• CO
2
dissolves in water and reacts with water to
produce carbonic acid, H 2 CO 3 , as shown below.
Figure 5. The bicarbonate buffer system.
• H
2
CO
3
is both the major acid produced by the
body, and its own buffer.
- Carbonic acid, due to its low pKa, completely
dissociates in blood and therefore, it is unable to
buffer and generate bicarbonate.
- However, carbonic acid can be replenished due to the
high concentration of dissolved CO 2
in body fluids.
- With such mechanism, dissolved CO 2
is in equilibrium
with the CO 2
present in the alveoli, thus the availability
of CO 2
can be increased or decreased by an
adjustment in the rate of breathing and the amount of
CO
2
expired. Therefore, CO 2
availability can be
regulated by respiration.
- In figure 6, the equation summarizes the bicarbonate
buffer system through the Henderson-Hasselbach
equation such that when there is an increase in
HCO 3
, there in an increase in pH; and, when there is
an increase in pCO 2,
there is a decrease in pH.
Figure 6. The relationship of pCO 2
and HCO 3
through the Henderson-Hasselbach equation.
2. Bicarbonate and Hemoglobin Buffer System in RBC
[𝐴 −]
[
]
Organic acids Inorganic acids
Contains Carbon eg.
Lactic acid, Ketone
bodies, Acetic acid,
Citric acid, Formic acid
Does not contain Carbon
eg. HCl*, HNO 3
*, H
2
SO
4
HCN, H
2
s
*strong acids
Volatile acids Non-volatile acids
Carbonic acids ; has to do
with respiration
Non-carbonic/ fixed acids
Excreted by LUNGS Excreted by KIDNEYS
13,000- 20,000 mmol/day 50-80 mmol/day
Carbonic acid Lactic acid, Phosphoric acid,
Sulfuric acid, Acetoacetic
acid,
Beta-hydroxybutyric acid
All acids produced in the body are nonvolatile except
carbonic acid.
Sources of Non-volatile acids in the body:
- Diet
Sulfuric acid (H 2
SO
4
- From sulfur containing amino acid (cysteine &
methionine)
® E.g. soybeans, beef, lamb, sunflowers
seeds, chicken, oats, pork, fish, cheese,
eggs, legumes, and kamut.
Phosphoric acid (H 3
PO
4
- From phosphoprotein/phospholipids
® foods containing lecithin
egg yolks, wheat germ, soy, milk,
and lightly cooked meats
- Intermediary metabolism
- CHO → lactic acid when O 2
is low
- Fat → ketoacids : acetoacetic (acetone) and Beta-
hydroxybutyric acid when DM is uncontrolled
Balance is done by 3 main organs:
1. LIVER
- A metabolically active organ which can significantly
produce or consume hydrogen ions; metabolizes
protein that produces hydrogen ions
- Ammonium is both detoxified in:
® Urea cycle
NH
4
→ urea + 2H + → acidification of the body
® Glutamine synthesis
NH
4
→ glutamine synthesis → H
is not produced
Glutamine is taken up by the kidneys
where H
+
excreted as NH 4
+
2. LUNGS
- Respiration reacts 1-3 minutes
- Medulla Oblongata in brain stem = respiratory center
- Can eliminate/cumulate VOLATILE ACIDS by
removing/retaining CO 2
• CO
2
- from decarboxylation in citric acid cycle
- CO 2 combines with H 2 O → carbonic ACID
- Hypoventilation – net gain (preserve CO 2
) → dec. pH
- Hyperventilation → net loss (release CO 2
) → inc. pH
3. KIDNEYS
- Reacts hours-days
- Only kidneys can clean the body from NON-
VOLATILE ACIDS
- 2 major activities – recycling and synthesis
Normally, all filtered HCO 3
are reabsorbed in the renal
tubules (proximal tubules) ( Recycling )
- Affects H+ ion excretion thru the formation of titratable
acids and ammonium ( Synthesis )
- In ACIDOSIS (dec. pH) → renal tubules generates
new HCO3 → inc. pH
In ALKALOSIS → all filtered HCO 3
are not
reabsorbed
→ HCO3 secreted via urine → dec. HCO 3
→ dec. pH
- Excretes acid in the form of H 2
PO
4
(dihydrogen
phosphate), HCO 3
and NH 3
(ammonia)
Buffer reaction within the tubular fluids (renal)
1. Bicarbonate titration – predominates in the proximal tubule 2. Phosphate titration – at the distal tubules
Diarrhea = additional of nonvolatile acids
3. HCO
3
loss in the stool
3. Ammonium titration – at the distal tubules Major precursor
of ammonia is the amino acid GLUTAMINE – contribute both
its amide and amino nitrogen in the formation of ammonia
- Glutamine is extracted from both the blood and the
tubular cells within the mitochondria, it is deaminated
by phosphate dependent glutaminase to glutamate
and ammonia
- Glutamate – deaminated to alpha ketoglutarate and
ammonia by glutamate dehydrogenase in the
presence of nicotinamide adenine dinucleotide group
- May also be produced by alanine and glycine that
may contribute their amino group to alpha
ketoglutarate by transamination to form glutamate
which again can be
deaminated
Glumerolus – site of filtration
In a patient where there is imbalance in the food intake or
internal metabolic disorders – net addition of 1 mEq/kg/day
E. ACID-BASE DISORDERS
Change in extracellular pH can be seen if:
- Renal or respiratory function is abnormal
- Acid/base overload overwhelms the capacity to
excrete
Acidemia
Dec. blood pH
Inc. H+ ion conc.
Alkalemia
Inc. Blood pH
Dec H+ ion
conc.
Acid base disturbance
- Condition that initially affect either HCO 3
or pCO 2
leading to a shift in pH from normal
- Evokes a compensatory response
Normal ABG Values
pH 7.35-7.
pCO 2
35-45 mmHg
HCO
3
21-28 mmHg
pO 2
80-100 mmHg
pH pCO 2
HCO
3
Respi.
Acidosis
Respi.
Alkalosis
Metab.
Acidosis
Metab
Alkalosis
Metabolic disorder → HCO 3
disturbance
Respiratory disorder → pCO 2 disturbance
Higher CO 2
→ lower pH (more acidic)
(CO 2 yields carboxylic ACID)
METABOLIC ACIDOSIS
• HCO
3
loss in diarrhea
- Seen in renal failure
- Buffering of non-carbonic acid like lactic acid (seen in
shock )
- Uncontrolled DM → diabetic ketoacidosis (DKA)
- Loss of alkali in GIT fistulas & drainage
- Compensatory is to lower pH by ventilation
- Ultimate restoration is renal excretion of excess acids
which will take several days
ANION GAP
- A means of approximation the total concentration of
anions other than Cl- and HCO 3 - in the plasma
- Sum of the major cations in the plasma minus the sum
of major anions
-]+[Cl-]) • Normal: ≤ 12
mEq/L
METABOLIC ALKALOSIS
- High HCO 3
- Loss of acid in vomiting and diureticmedication
- Nasogastric suctioning
- TPN infusion
