4.water

WATER, acids, bases and
buffers.
Explainatory video 
https://oke.io/6Vz1yj

INTRODUCTION
● What is Water
● Explainatory video  https://oke.io/6Vz1yj

INTRODUCTION
● Water is a transparent and nearly colourless chemical
substance that is the main constituent of earth’s
streams, lake, oceans and the fluids of most living
organisms.
● Covers 71% of the earth’s surface
● Colourless and odourless

● Life is inconceivable without water.
● Water constitutes 45%-75% of total human body
weight.
● It is distributed in intracellular and extracellular
compartments and provides a continous solvent phase
between body compartments.
● As the biological solvent, water plays a major role in
all aspects of metabolism:

● Absorption, transport, digestion, excretion as well as
maintenance of body temperature.
● Water is not just the solvent in biological reactions.
● Water is a good nucleofile and it is very often a direct
participant in reactions such as hydrolysis and
condensation
● The unique properties of water are derived from its
structure.

Structure of water
● H2O
● Water is a hydride of oxygen in which the highly
electronegative oxygen atom attracts the bonding
electrons from two hydrogen atoms.
● This forms a covalent bond as the electrons are being
shared by the two atoms.
● The oxygen molecule being more electronegative tends
to pull the electrons more to itself and away from the
hydrogen atom.

● Hence a partial negative charge on the oxygen atom
which has two unpaired share of electrons and a
partial positive charge on each of the hydrogen
atoms.
● This allows the water molecule to associate with four
others of its kind.
● Therefore a water molecule has a dipole structure.
●

Properties of water
physical properties.
▪ Colourless/transparent.
▪ Odourless
▪ Tasteless
▪ Explainatory video  https://oke.io/6Vz1yj

Properties of water
Water is the only common substance known to exist in 3
different states;
➢solid
➢liquid
➢gaseous.
Hence some properties which include;
● Boiling point
● Melting point
● Freezing point which are substantially high for a
molecule of its size.

● The unrivalled ability to form hydrogen bond is the
crucial fact to understanding its properties.
● Participation in H bonding by H2O is a phenomenon
of mutual reinforcement.

HYDROGEN BOND
● Neighboring liquid water molecules interact with one
another.
● The intermolecular bonding between water molecules
arises from the attraction between the partial
negative charge on the oxygen atom and the partial
positive charge on the hydrogen atom of adjacent
water molecules.
● This type of attraction involving a hydrogen atom is
known as hydrogen bond

● Hydrogen bonds contain a hydrogen atom between
two electronegative atoms (e.g., O and N).
● Hydrogen bonds are weaker than covalent bonds.
● However the cumulative effect of many hydrogen
bonds is equivalent to the stabilizing effect of covalent
bonds.
● In proteins, nucleic acids and water, hydrogen bonds
are essential to stabilize overall structure.
●

Chemical property of water.
● This include;
● Solvent property
● Colligative property
● Ionizing property

Solvent property of water.
● A solvent is simply a substance that can dissolve other
molecules and compounds which are known as solutes.
● A homogenous mixture of solvent and solute is called a
solution, and much of life’s chemistry takes place in
aqueous solutions, or solutions with water as the solvent.
● Due to its high ability to dissolve a wide range of solutes,
water is sometimes

called a ‘universal solvent’ however not entirely
accurate.
● Generally water is good at dissolving ions and polar
molecules, but poor at dissolving non polar
molecules.
● A polar molecule is one that’s neutral, or
uncharged, but has an asymmetric internal
distribution of charge, leading to partially positive
and partially negative regions.

● Because of its polarity, water can form electrostatic
interactions(charge –based attractions) with other
polar molecules and ions.
● The polar molecules and ions interact with the
partially positive and partially negative ends of water,
with positive charges attracting negative charges.

● Hydrophillic; simply put, are water-loving substances.
Examples of which are alcohol, solid sugar and salt.
● Hydrophobic; water-hating and hence insoluble e.g.
fats.
● Amphipathic molecules; compounds which are made
up of both substances. They have both hydrophobic
and hydrophilic properties.

● Amphipathic compounds are the molecules which
contain both hydrophobic groups (large nonpolar
hydrocarbon chains) and polar or ionic groups
(hydrophilic groups).
● They don’t dissolve in water as individual molecules
example is the interaction between detergent
molecules and water.
● When they reach a definite concentration (critic
micelle concentration) in water, they associate with
each other in submicroscopic aggregations of
molecules called micelles.

illustration
● Micelles have hydrophilic
groups on their exterior
(bonding with solvent water),
and hydrophobic groups
clustered in their interior.
● They occur in spherical shapes.

Amphipathic compounds.
micelle liposome

● Hydrophobic interactions are also weaker than covalent
bonds. However, many such interactions result in large,
stable structures.
● When amphipathic compounds are available at a
considerably higher concentration than critic micelle
concentration, they form liposome vesicles after the
sonication.
● Liposome vesicles are two-bilayer lipid spheres.

Colligative property
● Colligative properties; they are properties that
depend upon the concentration of molecules or ions,
but not upon the identity of the solute.
● This properties of water consists of;
● Freezing point depression
⚫Boiling point elevation
⚫Vapour pressure lowering
⚫Osmotic pressure effect.
⚫Explainatory video  https://oke.io/6Vz1yj

Example.
● Osmotic pressure is the pressure that must be applied
to the high concentration area to stop osmosis.
● This can be accomplished either physically by
applying force on one side of the system or
chemically , by changing a solute concentration.

Ionizing property
● Water demonstrates the tendency to form ions thus
its ability to conduct electricity.
● This occurs when the highly electro-negative oxygen
of a water molecule displaces or strips the hydrogen
molecule of its electron thus producing hydrogen
ion/proton(H+) and an hydroxyl ion (OH-).
● The free protons are immediately hydrated by a
neighbouring water molecule to hydronium ion,H30+.

Ionization Cntd....
● Since most hydrogen atoms in liquid water are hydrogen
bonded to a neighbouring water molecule, the hydration
of proton is an instantaneous process and in essence,
product of ionization is actually H30+ and OH-.

The ion product of water
● The dissociation of water into H+ and OH- occurs to
the extent that 10-7 mol H+ and 10-7 of OH- are
present at equilibrium in 1L of water at 25.
● The equilibrium constant for this process is
Keq=(H+) (OH-)/(H20).
● The molar concentration of H20 in pure water is
55.5 M.

Acid Base balance
Acid-base balance refers to the mechanisms the
body uses to keep its fluids close to neutral pH (that
is, neither basic nor acidic) so that the body can
function normally.
Arterial blood pH is normally closely regulated
to between 7.35 and 7.45.

The Acid-Base Balance
● Balance of H conc. in the ECF; maintaining the pH
within 7.35-7.45
● To achieve Homeostasis there has to be a balance
between :
The H Intake or Production
The H Removal
&

Why a balance ?
• A very tight control is needed for normal metabolic
functions. E.g. enzymatic activity, blood clotting and
neuromuscular activity.
• Hydrogen ions are the toxic end product of
metabolism and they adversely affect all physical and
biochemical cellular process in our body.
• The human body releases averagely 50-100mmol of
H+ daily into the ECF
• Explainatory video  https://oke.io/6Vz1yj

Acid: molecules containing H atoms that can release
(donate) H ions in solutions .
● Strong acids : - Completely dissociate : (HCL , H2SO4 )
● Weak acid : - Partially dissociate : ( H2CO3)
Base: An Ion that accept a H ion ; example of a base is
the Bicarbonate ( HCO3 ) .
Buffer: mixture of a weak acid and the salt of its
conjugate base that resists changes in pH when a strong
acid(base) is added to the solution
- As hydrogen ions are added some will combine with the
conjugate base and convert it to undissociated acid
Explainatory video  https://oke.io/6Vz1yj

Acid-Base Definitions
The removal of a proton (hydrogen ion) from an acid
produces its conjugate base, which is the acid with a
hydrogen ion removed, and the reception of a proton by
a base produces its conjugate acid, which is the base
with a hydrogen ion added

The body produces more acids than bases
● Acids taken in with foods
● Acids produced by metabolism of lipids and proteins
● Cellular metabolism produces CO2.
(CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3
- )

Lactic acid
Ketone bodies
Sulfuric acid
Phosphoric acid
• Intracellular metabolism
Volatile
acids
300~400L CO2 (15mol
H+)
Fixed
acids
50~100 mmol H+
•NH3 , sodium citrate, sodium lactate
Origin of acids Much more
Origin of bases less
CO2+H2O=H2CO3

pH Review
● pH is a measure of the H+ activity
● pH = negative log of the hydrogen ion concentration ( -
log [H+] )
● Range is from 0 – 14
● If [H+] is high, the solution is acidic; pH < 7
● If [H+] is low, the solution is basic or alkaline ; pH > 7
38

pH review: human system
- Homeostasis of pH is tightly controlled
- pH of ECF is between 7.35 and 7.45. Deviations,
outside this range affect membrane function,
alter protein function, etc.
- You cannot survive with a pH <6.8 or >7.7
• Acidosis- below 7.35
Alkalosis- above 7.45
CNS function deteriorates, coma, cardiac
irregularities, heart failure, peripheral
vasodilation, drop in Bp.

■ Given that normal body pH is slightly alkali( vis a vis
neutral pH and that normal metabolism produces
acidic waste products such as carbonic acid (carbon
dioxide reacted with water) and lactic acid, body pH is
constantly threatened with shifts toward acidity.
■ In normal individuals, pH is controlled by two major
and related processes; pH regulation and pH
compensation. Regulation is a function of the buffer
systems of the body in combination with the
respiratory and renal systems, whereas compensation
requires further intervention of the respiratory and/or
renal systems to restore normalcy.
pH review
contd

Mechanisms for acid-base regulation
Three Systems in the body :
1) - Buffers in blood .
2)- Respiration through the lungs .
3)- Excretion by the kidney .
● Two key organs for acid-base regulation are the lungs
and kidneys
● GIT ; stomach, pancreas, biliary cells: play minor roles-
assume greater impact in disorder states

H＋ load
ECF lung ICF Renal Bone
Buffers RBC Respiratory
control
Buffers
H+ excretion
bicarbonate
reabsorption
Release
bone salt
H＋－K＋
exchange
Hb
buffers
others
Ca2＋＋H2PO4−
In chronic
metabolic
acidosis
H2CO3→ CO2
Acid
excretion
Expiration
Immediately minutes hours days Very slow

Buffers
- Buffer systems act as first line of defense against
changes in the acid-base balance .
●Types:
*HCO3(regulated by Renal & Respiratory systems)
*Protein (plasma, intracellular etc)
*Phosphate (minor in the ECF but very important in urine)
*Hemoglobin
( NB; the proteinaceous matrix of bone is an
important buffer in chronic acidosis)
- A buffer is most effective in maintaining a pH near its pKa (±
one pH unit of its pK )
Examples; pKa - of phosphate= 6.8;
- of HCO3 = 6.1

● Despite the not too closeness to the pH of the
ECF(7.4), the HCO3 buffer system is the most
important ;
• because of its abundance( accounts for > 60%
of the blood buffering capacity)
• it is vital for efficient buffering of Hb buffer
which accounts for almost the rest of the
blood buffering capacity
- It is under the regulation of both the two important
organ systems (lungs & kidneys)
Buffers

Buffering system
2 ECF
Plasma NaHCO3/ H2CO3 NaPr/HPr* Na2HPO4/NaH2PO4
intercellular NaHCO3/ H2CO3 Na2HPO4/NaH2PO4
fluid
2 ICF** KPr/HPr K2HPO4/KH2PO4 KHCO3 /H2CO3
organic acids
2 RBC KHb/HHb KHbO2/HHbO2 K2HPO4/KH2PO4
KHCO3/ H2CO3
* HPr：protein； ** muscle cells。

buffering？
HA H+ + A−
Ka =
[ H+ ] × [ A− ]
[ HA ]
[ H+ ] = Ka ×
[ HA ]
[ A− ]
pH = pKa + lg
[ HA ]
[ A− ]

Schematic illustration of buffering
mechanism

Henderson-Hasselbalch equation：
pH = pKa ＋ log（[ HCO3－] /[ H2CO3]）
pH = pKa ＋ log（[ HCO3－] / α·PaCO2）
pH = 6.1 ＋ log（ 24 /0.226·5.32）
pH = 6.1 ＋ log（ 24 / 1.2）
pH = 6.1 ＋ 1.3
pH = 7.4
（α: the factor which relates PCO2 to the amount of CO2 dissolved in
plasma）

Respiratory Regulation of H+
● Rising plasma H+ causes deeper, rapid breathing which
decreases CO2 blood thereby decreasing H+ ions.

Renal mechanisms
● Bicarbonate reclamation
- important for maintaining the steady state
- reclaims filtered HCO3( almost completely)
- occurs majorly in the proximal tubule
- there is no net loss of H+
● Bicarbonate generation
- there is net loss of H+
• vital mechanism for correcting acidosis or fall in
pH

Some features of Phosphate buffer
● The phosphate buffer system increases hydrogen ion
excretion capacity to 30-40 mmol/24 hours
● In times of chronic overproduction of acid another
urine buffer system, Ammonia buffer comes into play

Bicarbonate generation
Not shown is the HCO3 that enters the ECF(blood)

Some features of NH3 buffer
● At normal intracellular pH most ammonia is present as
ammonium ions which can’t diffuse out of the cell
● Diffusion of ammonia out of the cell disturbs the equilibrium
between ammonia and ammonium ions causing more
ammonia to be formed
● Hydrogen ions formed at the same time!
● These are used up by the deamination of glutamine to
glutamate during gluconeogenesis

Respiratory mechanisms
- Tissue aerobic metabolism using O2 yields CO2
- Maintaining normal pH by maintaining constant pCO2
through gas exchange and ventilation .
- Controlled by chemoreceptors .
- The rate of respiration & CO2 elimination or retention is
regulated by these chemoreceptors (medulla, carotid &
aortic bodies)
pCO2 pH rate of respiration

Respiratory mechanisms
● Exhalation of carbon dioxide
● Powerful, but only works with volatile acids
● Doesn’t affect fixed acids like lactic acid
● CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3
-
● Body pH can be adjusted by changing rate and depth
of breathing
59

Summary
◆Buffers only provide a temporary solution.
◆Kidney: are the ultimate H+ ions balance. Slow
acting mechanisms can eliminate any imbalance
in H+ levels.
◆Lung: responds rapidly to altered plasma H+
concentrations, and keep blood levels under
control until the kidneys eliminate the
imbalance.

Definition of acid-base disorders
An acid base disorder is a change in the
normal value of extracellular pH that may result
when renal or respiratory function is abnormal
or when an acid or base load overwhelms
excretory capacity.
或

Simple Acid-Base Disorders
■Since PCO2 is regulated by respiration, abnormalities that primarily alter
the PCO2 are referred to as respiratory acidosis (high PCO2) and
respiratory alkalosis (low PCO2).
■In contrast, [HCO3¯] is regulated primarily by renal processes.
Abnormalities that primarily alter the [HCO3¯] are referred to as
metabolic acidosis (low [HCO3¯]) and metabolic alkalosis (high
[HCO3¯]).
Clinical disturbances of acid base metabolism classically are defined in
terms of the HCO3¯ /CO2 buffer system.
Acidosis – process that increases [H+] by increasing PCO2 or by reducing
[HCO3-]
Alkalosis – process that reduces [H+] by reducing PCO2 or by increasing
[HCO3-]
Henderson Hasselbalch equation:
pH = 6.1 + log [HCO3-]/ 0.03 PCO2

Disorders of Acid-base balance
● 4 components involved in the pathophysiology of
hydrogen ion disorders (acid-base disorders):
1. Generation
2.Buffering
3.Compensation
4.Correction
In clinical scenarios, these occur concurrently though over
different time courses

Disorders of Acid-base balance
Classification
● * Acidosis
- metabolic
- respiratory
● * Alkalosis
- metabolic
- respiratory

Acidosis
● Principal effect of acidosis is depression of the CNS
through ↓ in synaptic transmission.
● Generalized weakness
● Deranged CNS function the greatest threat
● Severe acidosis causes
●Disorientation
●coma
●Death
●Explainatory video  https://oke.io/6Vz1yj
65

Alkalosis
● Alkalosis causes over excitability of the central
and peripheral nervous systems.
● Numbness
● Lightheadedness
● It can cause :
● Nervousness
● muscle spasms or tetany
● Convulsions
● Loss of consciousness
● Death
66

Some causes of metabolic acidosis
● Ketoacidosis (diabetic, alcoholic)
● Poisoning (methanol, ethylene glycol, salicylate )
● Uremia
● Lactic acidosis
● Diarrhoea
● Carbonic anhydrase inhibitors
● Isoniazid toxicity
● Renal tubular acidosis(RTA) (type 1, 2 ,4)
● Inherited organic acidosis
● Fistulae (intestinal, pancreatic)
● Hyperkalaemia

Some causes of metabolic alkalosis
● Vomiting & gastric aspiration
● Cushing’s syndrome (excess cortisol production by the
zona fasciculata)
● Conn’s syndrome (primary hyperaldosteronism)
● Chronic alkali ingestion (milk-alkali syndrome etc)
● Drugs (e.g those that increase mineralocorticoid activity,
carbenoxolone)
● Hypokalaemia

Some causes of respiratory alkalosis
● High altitude
● Severe anaemia
● Respiratory stimulants
● Mechanical overventilation
● Gram-negative septicaemia (can be an early sign)
● Pulmonary diseases ( pulmonary embolism , pulmonary
oedema)
● Chronic liver disease(hepatic failure)
● Hyperventilation (anxiety, voluntary, panic disorders,
pregnancy )
● Fever
● Salicylates
● CNS infections (meningitis, encephalitis)
● Hyperthyroidism

Compensatory mechanisms
-If underlying problem is metabolic :
Hyperventilation and Hypoventilation mechanisms
will help through Respiratory Compensation .
-If the problem is Respiratory , then Renal
mechanisms will help through Metabolic
Compensation .
-However note that in metabolic disorders not
secondary to renal causes (i.e with intact renal
function), the kidneys will also help with
compensation.

Correction for Respiratory Alkalosis :
HCO3 reclamation/generation by kidneys
blood HCO3 decreases pH to normal value .
Excreted urine will be characterized by high HCO3.
Blood features : pH= normal; low HCO3 , low pCO2

Correction for Respiratory acidosis :
HCO3 reclamation/generation by the kidney
Blood HCO3 pH back to normal .
Blood features: pH = normal , high pCO2 , high HCO3
Urine will have low HCO3 conc.(low pH) .

Correction of Metabolic Alkalosis
● Depress ventilation Blood PCO2
pH back to normal .
Blood features:
PH=~ Normal
HCO3 = high
PCO2 = high

Correction for Metabolic Acidosis
- Stimulate ventilation ( Hyperventilation )
pCO2 pH back to normal .
• Renal compensation in adequate kidney function
Blood features :
pH =~ normal
HCO3 = Low
pCO2 = Low

Diagnosis of Acid-Base Imbalances
(1) Note whether the pH is low (acidosis) or high (alkalosis)
(2) Identify if it is respiratory or metabolic (CO2/HCO3)
(3) Identify if it is compensated or not.
75

Example 1
● A patient is in intensive care because he suffered a
severe myocardial infarction 3 days ago. The lab reports
the following values from an arterial blood sample:
● pH 7.3
● HCO3 = 20 mEq / L ( 22 - 26)
● pCO2 = 32 mm Hg (35 - 45)
What kind of acid-base disturbance is this ? What can you
say about compensatory mechanisms
76

Example 2
● 45yr old man admitted with a history of persistent
vomiting. He is a known dyspneic patient. On
examination he was obviously dehydrated with
shallow respiration. Lab findings on arterial blood gas
analysis are as stated below;
• pH : 7.56
• pCO2 : 54mmHg (35-45)
• HCO3 : 42mmol/L (22-26)
Discuss his H+ status

Answer.
● Patient 1; metabolic acidosis
● Compensated.
● Patient 2- metabolic alkalosis
● Compensated.

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