WATER, PRELIMINARIES
10/9/2025@Biochemistry 2025 2
➢Universal solvent
➢Can exist in 3 different forms:
Solid (ice), liquid (water), and gas (steam)
➢≈ 60 – 70% of human body weight
➢Most biochemical reactions occur in aqueous environment
➢10% water loss➔ serious disorders
➢25% loss ➔ death
➢Water is well adapted to its function in living
organisms/biological systems
PROPERTIES OF WATER
•Very polar, can dissolve hydrophilic molecules
•Oxygen is highly electronegative.
•LEADS TO UNEQUAL SHARING OF
BONDING ELECTRONS
•Its H-bonding contributes to its cohesiveness
with other molecules
•H-bond donor and acceptor. Effect on pH
•High BPS, MPS, heat of vaporization, surface
tension
10/9/2025@Biochemistry 2025 3
UNUSUAL AND UNIQUE PROPERTIES OF WATER
•BOILING POINT AND FREEZING POINT
•SURFACE TENSION, HEAT OF VAPORIZATION, AND VAPOR PRESSURE
•VISCOSITY AND COHESION
•SOLID STATE
•LIQUID STATE
•GAS STATE
•SOLVENT
10/9/2025@Biochemistry 2025 4
BOILING POINT AND FREEZING POINT
•BPS AND FPS DECREASE AS MOLECULAR SIZE DECREASES, BUT NOT FOR WATER:
•WATER REQUIRES MORE ENERGY TO BREAK ITS HYDROGEN BONDS BEFORE IT BOILS/
FREEZES:
•VITAL IN LIVING ORGANISMS LIVING IN WATER; AS THEY COULD DIE INSTANTLY
•ALSO VITAL FOR COOLING BODY TEMPERATURE VIA SWEATING.
10/9/2025@Biochemistry 2025 5
PROPERTIES OF WATER AND BIOLOGICAL
APPLICATIONS
Property Application(s)
1Is a liquid over a wide
temperature range
i.Chemical reactions readily occur in
liquids.
ii.Attractive medium for
microorganisms
2Excellent solvent Good for chemical reactions,
delivery of food materials & removal
3High ionizing solvent
(high dielectric constant)
Ionizes salts, makes conductive
solutions. Important in nerves &
excitable tissues
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Property Application(s)
4Has low viscosity (readily
flows)
Improved flowability, hence easy blood
circulation. Less strain on the heart
5High surface tension
(surface acts as tough coat
with tough film)
•Enables the lung alveoli to easily
collapse after inhalation.
6High heat capacity (large
amount of heat required to
raise its temperature)
Maintains body temp constant, Useful
for moving large amounts of heat in
the circulatory system.
10/9/2025@Biochemistry 2025 8
Property Application(s)
7High latent heat of
vaporization
Used by mammals in sweating
(body can lose heat if ambient
temps are above body temp.
8High heat of conductionHeat produced by biological
reactions can be removed,
preventing overheating
SURFACE TENSION, HEAT OF VAPORIZATION, AND
VAPOR PRESSURE
•SURFACE TENSION: HIGH, DUE TO THE HYDROGEN BONDS.
•HEAT OF VAPORIZATION: (~2260 KJ/KG) ➔VERY HIGH.
•VAPOUR PRESSURE: INVERSELY PROPORTIONAL TO INTERMOLECULAR
FORCES: WATER HAS STRONG INTERMOLECULAR FORCES = LOW V.P
10/9/2025@Biochemistry 2025 9
VISCOSITY AND COHESION AND ADHESION
•VISCOSITY: THE PROPERTY OF FLUID HAVING HIGH RESISTANCE
TO FLOW: WATER IS VISCOUS DUE TO STRONGER
INTERMOLECULAR FORCES
•COHESION: INTERMOLECULAR FORCES BETWEEN LIKE
MOLECULES; THIS IS WHY WATER MOLECULES ARE ABLE TO
HOLD THEMSELVES TOGETHER IN A DROP.
•DUE TO ITS POLARITY.
•IMPORTANCE : ????
10/9/2025@Biochemistry 2025 10
10/9/2025@Biochemistry 2025 11
HYDROGEN BONDING OF WATER
ONE H
2O MOLECULE CAN ASSOCIATE
WITH 4
OTHER H
2O MOLECULES
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Crystal lattice of ice
Ice: 4 H-bonds per
water molecule
Water: 2.3 H-bonds per
water molecule
SOLID STATE AND LIQUID STATE OF WATER
•WATER IS MORE DENSE THAN ICE: WHY?
•AS WATER COOLS BELOW 4
0
C, HYDROGEN BONDS REARRANGE
THEMSELVES INTO AN OPEN CRYSTALLINE, HEXAGONAL STRUCTURE,
MAKING WATER MOLECULES TO BE HELD FURTHER APART
•MOLECULES ARE HELD TIGHTLY PACKED IN WATER’S LIQUID STATE:
BEING HELD BY HYDROGEN BONDS, MOVING FREELY.
•WHAT DOES THIS IMPLY? WHY IS IT IMPORTANT FOR LIVING ORGANISMS?
10/9/2025@Biochemistry 2025 13
GAS STATE
•AS WATER BOILS, THE HYDROGEN BONDS ARE BROKEN AS PARTICLES
MOVE FASTER.
•LACK OF HYDROGEN BONDS EXPLAINS WHY STEAM CAUSES WORSE
BURNS WATER.
•ALL THE ENERGY TO BREAK THE HYDROGEN BONDS IS CONTAINED IN STEAM.
•AND AS STEAM IS CONVERTED TO LIQUID WATER, MORE HEAT ENERGY IS
RELEASED.
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WATER DISSOLVES POLAR COMPOUNDS
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Solvation shell
or
hydration shell
I.In solution, salts exist as ions (e.g: Na
+
, Cl
-
)
II.The ionic salt dissolves in water by polarity.
III.The polar water molecules surround the individual salt ions by orientation
of water molecules, forming hydration shells.
NON-POLAR SUBSTANCES ARE INSOLUBLE IN WATER
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Many lipids are amphipathic
MICELLES
•AN AGGREGATE OF MOLECULES IN A COLLOIDAL SOLUTION, SUCH AS
THOSE FORMED BY DETERGENTS.
•A TYPICAL MICELLE INAQUEOUS SOLUTIONFORMS AN AGGREGATE
WITH THEHYDROPHILIC"HEAD" REGIONS IN CONTACT WITH
SURROUNDINGSOLVENT, SEQUESTERING THEHYDROPHOBIC SINGLE-
TAIL REGIONS IN THE MICELLE CENTER.
10/9/2025@Biochemistry 2025 17
HOW DETERGENTS WORK?
10/9/2025@Biochemistry 2025 18
IONISATION OF WATER
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K
eq, K
w and pH
H
2O is the medium of biological systems
Dissociation of ions from biological molecules occurs in H
2O.
Water is essentially a neutral molecule but will ionize to a small degree.
H
2O H
+
+ OH
-
IONIZATION OF WATER
THIS EQUILIBRIUM CAN BE CALCULATED AS FOR ANY REACTION:
10/9/2025@Biochemistry 2025 20
H
2O + H
2O H
3O
+
+ OH
-
H
2O H
+
+ OH
-
K
eq= [H
+
] [OH
-
]
[H
2O]
[H
2O] K
eq = [H
+
] [OH
-
]
K
eq=1.8 X 10
-16
M
[H
2O] = 55.5 M
(1.8 X 10
-16
M)(55.5 M ) = [H
+
] [OH
-
]
1.0 X 10
-14
M
2
= [H
+
] [OH
-
] = K
w
K
w - (ion product/ dissociation constant)
If [H
+
]=[OH
-
] then [H
+
] = 1.0 X 10
-7
•K
W (ION PRODUCT/ DISSOCIATION CONSTANT):
K
W = [H
+
][OH
–
]
•IN PURE WATER, TO WHICH NO ACIDS OR BASES HAVE BEEN ADDED:
K
W = 1 X 10
–14
M
2
AT ROOM TEMPERATURE.
HENCE 10
–14
= [H
+
][OH
–
]
10/9/2025@Biochemistry 2025 21
CALCULATE THE PH OF SOLUTION
•FROM 10
–14
= [H
+
][OH
–
] AND
•TAKING LOG;
–14 LOG
10 = LOG[H
+
] + LOG[OH
–
]
• -14 = LOG[H
+
] + LOG[OH
–
]
• 14 = -LOG[H
+
] - LOG[OH
–
]
•THEREFORE, 14 = PH + POH
•AT NEUTRALITY, [H
+
] = [OH
-
] = 1 X 10
–7
M
•THUS PH = 7, AND ALSO POH = 7.
•NOTE: PH IS THE NEGATIVE LOG OF HYDROGEN ION CONCENTRATION
OF ANY SOLUTION.
10/9/2025@Biochemistry 2025 22
pH = –log[H
+
]
pOH = -log[OH
–
]
BIOLOGICAL SOLUTIONS
•BLOOD
•URINE
•SEA WATER
•INTRACELLULAR FLUID (FLUID WITHIN CELLS)
•EXTRACELLULAR FLUID (FLUID BETWEEN CELLS)
10/9/2025@Biochemistry 2025 23
PH SCALE
•DEVISED BY SORENSON (1902)
• [H+] CAN RANGE FROM 1M AND
1 X 10-14M
• USING A LOG SCALE SIMPLIFIES
NOTATION
• PH = -LOG [H+]
•NEUTRAL PH = 7.0
10/9/2025@Biochemistry 2025 24
BIOLOGICAL SIGNIFICANCE OF PH
•H
+
IS ONE OF THE MOST IMPORTANT IONS IN BIOLOGICAL SYSTEMS.
ITS CONC. AFFECTS CELLULAR AND ORGANISMAL PROCESSES AS ALL METABOLIC PROCESSES ARE PH DEPENDENT.
1.STRUCTURE AND FUNCTION OF PROTEINS DEPENDS ON IONIC INTERACTIONS WHICH ARE PH DEPENDENT.
2.MOVEMENT OF IONS ACROSS MEMBRANES DEPENDS UPON THEIR NET CHARGE AS DETERMINED BY PH.
3.THE IONIC STATE OF THE NUCLEIC ACIDS, LIPIDS, MUCOPOLYSACCHARIDES ARE DETERMINED BY PH.
4.ALL ENZYMES FUNCTION BEST WITHIN OPTIMUM PH RANGE.
5.O
2 & CO
2 TRANSPORT, RELEASE/GASEOUS EXCHANGE ARE PH DEPENDENT.
6.THE [H
+
] ALSO PLAYS A ROLE IN ENERGY GENERATION AND ENDOCYTOSIS.
10/9/2025@Biochemistry 2025 25
ACIDS & BASES
•ACID–BASE BALANCE
•PH OF BODY FLUIDS IS ALTERED BY THE INTRODUCTION OF ACIDS OR BASES
•ACIDS AND BASES MAY BE STRONG OR WEAK
•STRONG ACIDS DISSOCIATE COMPLETELY (ONLY HCL IS RELEVANT
PHYSIOLOGICALLY)
•WEAK ACIDS DO NOT DISSOCIATE COMPLETELY AND THUS AFFECT THE PH LESS
COMPARED TO STRONG ACIDS (E.G. CARBONIC ACID)
10/9/2025@Biochemistry 2025 26
WEAK ACIDS AND BASES EQUILIBRIA
•STRONG ACIDS / BASES – DISSOCIATE COMPLETELY
•WEAK ACIDS / BASES – DISSOCIATE ONLY PARTIALLY
•THE PH DEPENDS ON THE DEGREE OF DISSOCIATION
•ENZYME ACTIVITY IS SENSITIVE TO PH
•WEAK ACID/BASES PLAY IMPORTANT ROLE IN PROTEIN STRUCTURE/FUNCTION.
10/9/2025@Biochemistry 2025 27
K
A
•IN BIOLOGICAL PROCESSES VARIOUS WEAK ACIDS AND BASES ARE ENCOUNTERED, E.G. THE
ACIDIC AND BASIC AMINO ACIDS, NUCLEOTIDES, PHOSPHOLIPIDS, ETC.
•WEAK ACIDS AND BASES IN SOLUTION DO NOT FULLY DISSOCIATE AND, THEREFORE, THERE IS
AN EQUILIBRIUM BETWEEN THE ACID AND ITS CONJUGATE BASE.
•THIS EQUILIBRIUM CAN BE CALCULATED AND IS TERMED THE EQUILIBRIUM CONSTANT = K
A.
•K
A IS ALSO REFERRED TO AS THE DISSOCIATION CONSTANT.
10/9/2025@Biochemistry 2025 28
ACID/CONJUGATE BASE PAIRS
10/9/2025@Biochemistry 2025 29
HA + H
2O A
-
+ H
3O
+
HA A
-
+ H
+
HA = acid ( donates H
+
)
A
-
= Conjugate base (accepts H
+
)
K
a = [H
+
][A
-
]
[HA]
K
a & pK
a value describe tendency
to loose H
+
large K
a = stronger acid
small K
a = weaker acid
pK
a = - log K
a
PKA VALUES DETERMINED BY TITRATION
10/9/2025@Biochemistry 2025 30
PHOSPHATE
HAS THREE
IONIZABLE H
+
AND THREE
PKAS
10/9/2025@Biochemistry 2025 31
BUFFERS
•BUFFERS ARE AQUEOUS SYSTEMS THAT RESIST CHANGES IN PH WHEN SMALL AMOUNTS OF A
STRONG ACID OR BASE ARE ADDED.
•A BUFFERED SYSTEM CONSIST OF A WEAK ACID AND ITS CONJUGATE BASE.
•THE MOST EFFECTIVE BUFFERING OCCURS AT THE REGION OF MINIMUM SLOPE ON A
TITRATION CURVE
(I.E. AROUND THE PKA).
•BUFFERS ARE EFFECTIVE AT PHS THAT ARE WITHIN +/-1 PH UNIT OF THE PKA
10/9/2025@Biochemistry 2025 32
BUFFERS
•AT PK
A THE PH OF A SOLUTION DOES NOT CHANGE APPRECIABLY EVEN WHEN LARGE
AMOUNTS OF ACID OR BASE ARE ADDED. THIS PHENOMENON IS KNOWN AS BUFFERING.
•DISSOLVED COMPOUNDS THAT STABILIZE PH BY PROVIDING OR REMOVING H
+
•WEAK ACIDS OR WEAK BASES THAT ABSORB OR RELEASE H
+
ARE BUFFERS
10/9/2025@Biochemistry 2025 33
BUFFER SYSTEMS
•BUFFER SYSTEM: CONSISTS OF A COMBINATION OF A WEAK
ACID AND THE ANION RELEASED BY ITS DISSOCIATION (ITS
CONJUGATE BASE)
•THE ANION FUNCTIONS AS A WEAK BASE:
H
2CO
3 (ACID) H
+
+ HCO
3
-
(BASE)
•IN SOLUTION, MOLECULES OF WEAK ACID EXIST IN
EQUILIBRIUM WITH ITS DISSOCIATION PRODUCTS (MEANING
YOU HAVE ALL THREE SPECIES IN PLASMA)
10/9/2025@Biochemistry 2025 34
HENDERSON-HASSELBACH EQUATION
.
10/9/2025@Biochemistry 2025 35
1) K
a = [H
+
][A
-
]
[HA]
2) [H
+
] = K
a [HA]
[A
-
]
3) -log[H
+
] = -log K
a -log [HA]
[A
-
]
4) -log[H
+
] = -log K
a +log [A
-
]
[HA]
pH = pK
a+log [A
-
]
[HA]
HA = weak acid
A
-
= Conjugate base
* This equation describes
the relationship between
pH, pKa and buffer
concentration
5)
CASE WHERE 10% ACETATE ION, 90% ACETIC ACID
10/9/2025@Biochemistry 2025 36
• pH = pK
a + log
10
[
0.1 ]
¯¯¯¯¯¯¯¯¯
[0.9]
•pH = 4.76 + (-0.95)
•pH = 3.81
pH = pK
a + log
10
[0.5 ]
[0.5]
•pH = 4.76 + 0
•pH = 4.76 = pK
a
•i.e. at neutral point pH is
equal to pKa
•Also, there is maximum
buffering
CASE WHERE 50% ACETATE ION 50% ACETIC ACID
10/9/2025@Biochemistry 2025 37
•pH = pK
a + log
10
[0.9 ] /0.1
¯¯¯¯¯¯¯¯¯¯
[0.1]
•pH = 4.76 + 0.95
•pH = 5.71
CASE WHERE 90% ACETATE ION 10% ACETIC ACID
10/9/2025@Biochemistry 2025 38
•QUESTION 1. CALCULATE THE PH OF A SOLUTION CONTAINING A MIXTURE OF 0.2M ACETIC
ACID AND 0.15M SODIUM ACETATE. THE PKA OF ACETIC ACID IS 4.76
•QUESTION 2. CALCULATE THE RATIO OF LACTIC ACID TO LACTATE REQUIRED IN A BUFFER
SYSTEM OF PH 6.5. THE PKA OF LACTIC ACID IS 3.86
10/9/2025@Biochemistry 2025 40
3 MAJOR PHYSIOLOGICAL BUFFER SYSTEMS
1.PROTEIN BUFFER SYSTEMS:
•HELP REGULATE PH IN EXTRACELLUAR FLUID (ECF) AND INTRACELLULAR
FLUID (ICF)
•INTERACT EXTENSIVELY WITH OTHER BUFFER SYSTEMS
2.CARBONIC ACID–BICARBONATE BUFFER SYSTEM:
•MOST IMPORTANT BUFFER OF BLOOD (ECF)
3.PHOSPHATE BUFFER SYSTEM:
•BUFFERS PH OF ICF AND URINE
10/9/2025@Biochemistry 2025 41
BUFFER SYSTEMS IN BODY FLUIDS
10/9/2025@Biochemistry 2025 42
Figure 27–7
1. PROTEIN BUFFER SYSTEMS
•AMINO ACIDS IN PROTEIN BUFFER SYSTEMS
•DEPEND ON FREE AND TERMINAL AMINO ACIDS
•RESPOND TO PH CHANGES BY ACCEPTING OR RELEASING H
+
•IF PH RISES:
•CARBOXYL GROUP OF AMINO ACID DISSOCIATES, ACTING AS WEAK ACID, RELEASING A
HYDROGEN ION
•IF PH DROPS:
•CARBOXYLATE ION AND AMINO GROUP ACT AS WEAK BASES
•ACCEPT H
+
FROM CARBOXYL GROUP AND AMINO ION
10/9/2025@Biochemistry 2025 43
10/9/2025@Biochemistry 2025 44
PROTEIN BUFFERS (MOST HAVE PKA = 7.4)
•THESE INCLUDE HAEMOGLOBIN, SERUM ALBUMINS AND OTHER PLASMA
PROTEINS, PROTEINS IN INTERSTITIAL FLUID AND IN THE INTRACELLULAR
FLUID (ICF)
•SEVERAL OF THESE GROUPS HAVE PKA VALUE AROUND 7.4.
•SINCE PROTEINS ARE PRESENT IN SIGNIFICANT CONCENTRATIONS IN LIVING ORGANISMS, THEY ARE
IMPORTANT POWERFUL BUFFERS;
•E.G. THE HAEMOGLOBIN, WHICH IS MOST ABUNDANT MOLECULE IN RED BLOOD CELLS. BECAUSE OF ITS
STRUCTURE AND CELLULAR CONCENTRATION, HAEMOGLOBIN PLAYS A MAJOR ROLE IN MAINTAINING BLOOD
PH.
10/9/2025@Biochemistry 2025 45
THE HEMOGLOBIN BUFFER SYSTEM
•VERY IMPORTANT AND 1
ST
DEFENSE MECHANISM AGAINST ACID – BASE IMBALANCE BUFFER
SYSTEM
•TRANSPORTS CO
2 & O
2
•WORKS MORE EFFECTIVELY WITH THE BICARBONATE BUFFER SYSTEM
•WORKS IN BOTH THE LUNGS AND TISSUES
10/9/2025@Biochemistry 2025 46
•CO
2 DIFFUSES ACROSS RBC MEMBRANE:
•NO TRANSPORT MECHANISM REQUIRED
•AS CARBONIC ACID DISSOCIATES:
•BICARBONATE IONS DIFFUSE INTO PLASMA
•IN EXCHANGE FOR CHLORIDE IONS (CHLORIDE SHIFT)
•HYDROGEN IONS ARE BUFFERED BY HEMOGLOBIN MOLECULES
•THE ONLY INTRACELLULAR BUFFER SYSTEM WITH AN IMMEDIATE EFFECT ON ECF PH
•HELPS PREVENT MAJOR CHANGES IN PH WHEN PLASMA P
CO
2
IS RISING OR FALLING
10/9/2025@Biochemistry 2025 47
2. THE CARBONIC ACID–BICARBONATE BUFFER SYSTEM
•FORMED BY CARBONIC ACID AND ITS DISSOCIATION PRODUCTS
•PREVENTS CHANGES IN PH CAUSED BY ORGANIC ACIDS AND FIXED ACIDS IN ECF/BLOOD
•H
+
GENERATED BY ACID PRODUCTION COMBINES WITH BICARBONATE IN THE PLASMA
•THIS FORMS CARBONIC ACID, WHICH DISSOCIATES INTO CO
2 WHICH IS BREATHED OUT
10/9/2025@Biochemistry 2025 48
INTERRELATIONSHIP OF THE BICARBONATE AND HAEMOGLOBIN
BUFFER SYSTEMS
10/9/2025@Biochemistry 2025 49
BICARBONATE BUFFER (PKA = 6.1)
•IT IS A CARBONIC ACID/BICARBONATE (H
2CO
3/HCO
3
-
) BUFFER SYSTEM.
•IT IS THE MOST IMPORTANT BUFFER SYSTEM IN THE BODY (PLASMA AND ECF) DESPITE THE FACT
THAT BICARBONATE HAS PKA OF 6.1 FAR BELOW THE PHYSIOLOGICAL PH 7.4
•IT IS SO IMPORTANT BECAUSE IT RESPONDS VERY FAST TO CHANGES IN PLASMA PH
THROUGH LOSS OF CARBON DIOXIDE IN THE LUNGS AND BICARBONATE IN THE URINE
THROUGH THE KIDNEYS.
•CO
2 REACTS WITH WATER TO FORM CARBONIC ACID
10/9/2025@Biochemistry 2025 50
•FROM 7.4 = 6.1 + LOG [BICARBONATE
]
[CARBONIC ACID]
•THE RATIO OF HCO
3
-
TO CO
2 REQUIRED TO MAINTAIN THE BLOOD PH OF 7.4 IS REGULATED:
•CARBON DIOXIDE CONC. IS ADJUSTED BY CHANGES IN THE RATE OF RESPIRATION
•BICARBONATE CONC. IS REGULATED BY THE KIDNEYS; IF THE [HCO
3
-
] DECREASES, THE KIDNEYS
REMOVE H
+
FROM THE BLOOD TRIGGERING A SHIFT TO THE RIGHT; INCREASING [HCO
3
-
].
•WHEN EXCESS HCO
3
-
IONS ARE PRODUCED, THEY ARE EXCRETED BY THE KIDNEYS TRIGGERING
A SHIFT TO THE LEFT.
10/9/2025@Biochemistry 2025 51
Figure 27–9
THE CARBONIC ACID–BICARBONATE BUFFER SYSTEM
10/9/2025@Biochemistry 2025 52
LIMITATIONS OF THE CARBONIC ACID BUFFER SYSTEM
1.HARD TO PROTECT ECF FROM CHANGES IN PH THAT RESULT FROM ELEVATED OR
DEPRESSED LEVELS OF CO
2 (BECAUSE CO
2 IS PART OF IT)
2.FUNCTIONS ONLY WHEN RESPIRATORY SYSTEM AND RESPIRATORY CONTROL CENTERS ARE
WORKING NORMALLY
3.ABILITY TO BUFFER ACIDS IS LIMITED BY AVAILABILITY OF BICARBONATE IONS
10/9/2025@Biochemistry 2025 53
3. THE PHOSPHATE BUFFER SYSTEM
•CONSISTS OF ANION H
2PO
4
—
(A WEAK ACID)
•WORKS LIKE THE CARBONIC ACID–BICARBONATE BUFFER SYSTEM
•IS IMPORTANT IN BUFFERING PH OF ICF
10/9/2025@Biochemistry 2025 54
3. PHOSPHATE BUFFER (PKA = 7.2)
•PHOSPHATE BUFFER CONSISTS OF WEAK ACID CONJUGATE BASE PAIR (H
2PO
4
-
/ HPO
4
2-
)
• H
2PO
4
-
→ H
+
+ HPO
4
2-
•DIHYDROGEN PHOSPHATE HYDROGEN PHOSPHATE
•IT HAS A PKA OF 7.2. ALTHOUGH THE BLOOD PH IS 7.4, CLOSE TO THE PHOSPHATE BUFFER
PKA OF 7.2 HENCE LOOKING A PERFECT BUFFER, THE CONCENTRATION OF H
2PO
4
-
AND
HPO
4
2-
IN BLOOD ARE TOO LOW TO HAVE A MAJOR EFFECT.
•HOWEVER, THE CONCENTRATION OF PHOSPHATE BUFFER IN INTRACELLULAR FLUID IS APPROX.
75MEQ/L WHILE IT IS 4MEQ/L IN BLOOD.
•IT IS THEREFORE AN IMPORTANT BUFFER IN INTRACELLULAR FLUID (ICF).
10/9/2025@Biochemistry 2025 55
PROBLEMS WITH BUFFER SYSTEMS
•PROVIDE ONLY TEMPORARY SOLUTION TO ACID–BASE
IMBALANCE
•DO NOT ELIMINATE H
+
IONS
•SUPPLY OF BUFFER MOLECULES IS LIMITED
10/9/2025@Biochemistry 2025 56
MAINTENANCE OF
ACID–BASE BALANCE
•REQUIRES BALANCING H
+
GAINS AND LOSSES
•FOR HOMEOSTASIS TO BE PRESERVED, CAPTURED H
+
MUST EITHER BE:
a)PERMANENTLY TIED UP IN WATER MOLECULES THROUGH CO
2 REMOVAL AT LUNGS OR
b)REMOVED FROM BODY FLUIDS THROUGH SECRETION AT KIDNEY
•THUS, PROBLEMS WITH EITHER OF THESE ORGANS LEADS TO PROBLEMS
WITH ACID/BASE BALANCE
•COORDINATES ACTIONS OF BUFFER SYSTEMS WITH:
•RESPIRATORY MECHANISMS
•RENAL MECHANISMS
10/9/2025@Biochemistry 2025 57
PH IMBALANCES
•ACIDOSIS: PHYSIOLOGICAL STATE RESULTING FROM ABNORMALLY LOW PLASMA PH
•ALKALOSIS: PHYSIOLOGICAL STATE RESULTING FROM ABNORMALLY HIGH PLASMA PH
•BOTH ARE DANGEROUS BUT ACIDOSIS IS MORE COMMON BECAUSE MOST CELLULAR
ACTIVITIES GENERATE ACIDS
•WHY IS PH SO IMPORTANT?
10/9/2025@Biochemistry 2025 58
•THE NORMAL BLOOD PH IS 7.4 BUT MAY VARY BETWEEN 7.35 & 7.45 DESPITE MANY ACIDIC OR
BASIC WASTE PRODUCTS DISSOLVED IN IT.
•CERTAIN DISEASE PROCESSES RESULT IN PH CHANGES WHICH IF NOT CORRECTED CAN LEAD TO
COMPLICATIONS.
•ACIDAEMIA – IS THE CONDITION DEFINED BY THE BODY’S ARTERIAL PH BELOW 7.35.
•THE PATHOLOGICAL STATE THAT RESULTS INTO ACIDAEMIA IS REFERRED TO AS ACIDOSIS.
•ALKALEMIA – IS THE CONDITION DEFINED BY THE BODY’S ARTERIAL PH ABOVE 7.45.
•THE PATHOLOGICAL STATE THAT RESULTS INTO ALKALEMIA IS REFERRED TO AS ALKALOSIS.
10/9/2025@Biochemistry 2025 59
10/9/2025@Biochemistry 2025 60
DETECTION OF ACIDOSIS AND ALKALOSIS
•INCLUDES BLOOD TESTS FOR PH, P
CO
2
AND HCO
3
—
LEVELS:
•RECOGNITION OF ACIDOSIS OR ALKALOSIS
•CLASSIFICATION AS RESPIRATORY OR METABOLIC
10/9/2025@Biochemistry 2025 61
➢ACIDOSIS/ ALKALOSIS MAY BE METABOLIC OR RESPIRATORY IN ORIGIN:
•ALL METABOLIC DISORDERS RESULT FROM IMBALANCE OF BICARBONATE IONS OR
METABOLISM.
•ALL RESPIRATORY DISORDERS RESULT FROM IMBALANCE OF PCO
2 OR RESPIRATION.
•IN CASE OF ANY OF THE ABOVE IMBALANCES, THE BODY RESPONDS WITH A
COMPENSATORY MECHANISM WHICH MAY BE;
•RESPIRATORY COMPENSATORY MECHANISM OR
•METABOLIC COMPENSATORY MECHANISM
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A) RESPIRATORY ACIDOSIS
➢MOST COMMON ACID/BASE PROBLEM:
➢CHARACTERIZED BY LOWERING OF BLOOD PH (BELOW 7.35)
➢DUE TO INCREASE IN PCO
2 IN BLOOD
➢IT RESULTS FROM FAILURE OF THE LUNGS TO ELIMINATE CO
2.
•DEVELOPS WHEN THE RESPIRATORY SYSTEM CANNOT ELIMINATE ALL CO
2 GENERATED BY
PERIPHERAL TISSUES
•PRIMARY SIGN:
•LOW PLASMA PH DUE TO HYPERCAPNIA (HIGH[CO
2])
•PRIMARILY CAUSED BY HYPOVENTILATION
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RESPIRATORY ACIDOSIS
•SECONDARY CAUSES;
✓OBSTRUCTIVE PULMONARY DISEASE, SHORTNESS OF BREATH AND COUGH
✓EMPHYSEMA - DAMAGED ALVEOLI ➔ SHORTNESS OF BREATH
✓PNEUMONIA, INFLAMMATORY INFECTION OF ALVEOLI
✓CARDIAC DISEASE ETC.
✓DRUGS E.G. MORPHINE, ALCOHOL RESULT INTO DECREASED VENTILATION.
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COMPENSATION MECHANISM
HIGH PCO
2 IS COMPENSATED BY:
•RESPIRATORY COMPENSATION I.E INCREASED RESPIRATORY
RATE
•BUFFERING BY NON-CARBONIC ACID BUFFERS (ACCEPT H
+
),
•INCREASED H
+
SECRETION
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RESPIRATORY COMPENSATION FOR ACIDOSIS
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Figure 27–12a
B) RESPIRATORY ALKALOSIS
•INCREASED BLOOD PH ABOVE 7.45.
•IS DUE TO LOW PCO
2 IN BLOOD/TOO MUCH LOSS OF CO
2
THIS RESULTS FROM;
✓HYPERVENTILATION (PRIMARILY CAUSE)
✓DEEP BREATHES DUE TO ASTHMA, ANXIETY OR FEVER ETC.
✓STRESS/PANIC,
✓HIGH ALTITUDE
•LEAST CLINICALLY RELEVANT
•COMPENSATED BY HYPOVENTILATION
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C) METABOLIC ACIDOSIS
➢THIS IS THE LOWERING OF BLOOD PH (BELOW 7.35)
DUE TO LOW BICARBONATE IONS (HCO
3
-
). THIS
RESULTS FROM:
✓EXCESSIVE PRODUCTION OF ORGANIC ACIDS IN
TISSUES E.G. KETO ACIDS IN STARVATION AND DIABETES
MELLITUS, LACTIC ACID IN ANAEROBIC RESPIRATION.
✓INCREASED LOSS OF BASE SUCH AS BICARBONATE
FROM BODY FLUIDS
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METABOLIC ACIDOSIS
✓KIDNEY FAILURE TO EXCRETE ACIDIC METABOLITES AS IN RENAL FAILURE
•IMPAIRED H
+
EXCRETION AT KIDNEYS
•CAUSED BY KIDNEY DAMAGE, OVERUSE OF DIURETICS/DRUGS THAT STOP NA+ AT THE EXPENSE OF
H
+
SECRETION
•SEVERE BICARBONATE LOSS (DIARRHEA – LOSS OF BICARBONATE FROM PANCREAS, LIVER
THAT WOULD HAVE BEEN REABSORBED) HENCE LOWERING THE PH.
•IF THE BLOOD PH FALL BELOW 7, THE CENTRAL NERVOUS SYSTEM BECOMES
DEPRESSED, A CONDITION THAT RESULTS IN COMA AND EVENTUAL DEATH.
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METABOLIC ACIDOSIS
•SECOND MOST COMMON ACID/BASE PROBLEM
•RESPIRATORY AND METABOLIC ACIDOSIS ARE TYPICALLY
LINKED:
•LOW O
2 GENERATES LACTIC ACID
•HYPOVENTILATION LEADS TO LOW PO
2
•COMPENSATED BY
•RESPIRATORY: INCREASED RR (ELIMINATE CO
2)
•RENAL: SECRETE H
+
, REABSORB AND GENERATE HCO
3
-
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D) METABOLIC ALKALOSIS
•INCREASED BLOOD PH ABOVE 7.45.
•CAUSED BY ELEVATED HCO
3
-
CONCENTRATIONS
•REDUCED [H
+
] CAUSES ALKALOSIS
•CAUSES:
•LOSS OF HYDROGEN IONS– MOST OFTEN OCCURS VIA TWO MECHANISMS, EITHER VOMITING
OR VIA THE KIDNEY.
•VOMITINGRESULTS IN THE LOSS OFHYDROCHLORIC ACID(HYDROGEN AND CHLORIDE IONS)
WITH THE STOMACH CONTENTS.
•SEVERE VOMITING ALSO CAUSES LOSS OF POTASSIUM (HYPOKALEMIA) AND SODIUM
(HYPONATREMIA).
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COMPENSATION:
•RESPIRATORY: REDUCED RR
•THE KIDNEYS COMPENSATE FOR THESE LOSSES BY RETAINING
SODIUM IN THE COLLECTING DUCTS AT THE EXPENSE OF
HYDROGEN IONS (SPARING SODIUM/POTASSIUM PUMPS TO
PREVENT FURTHER LOSS OF POTASSIUM), LEADING TO
METABOLIC ALKALOSIS.
•INCREASED HCO
3
-
LOSS AT KIDNEY, RETENTION OF HCL
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