1.0 Biophysical Chemistry.pdf 12323323w46

1.0 Biophysical Chemistry
Dr. Sepiso K. Masenga Lectures ~ Mulungushi University
~ smasenga@mu.ac.zm
Mulungushi University
School of Medicine and Health Sciences
Biomedical Sciences Program
Biochemistry BMB 230
Dr. Sepiso K. Masenga

Note
•Lectures will emphasize clinical aspect commensurate
with academic level and programme
•Attend lectures + Tutorial sessions to assist
understanding of lecture notes
•Tutorial sessions will involve question and answer
practice sessions to guide areas you need to
concentrate
~ smasenga@mu.ac.zm

Unit 1 Topic Outline
•1.1.Properties of water for biochemical reactions
•1.2.Physiological buffers
•1.3.Acids and bases
•1.4.Role of physiological buffers
~ smasenga@mu.ac.zm

OBJECTIVES
•Describe the properties of water and fundamental
principals of interactions and bonds
• Describe pH and its relation to acidity and alkalinity
•Explain the Biomedical application of Water and pH
in disease
•Explain the role of physiological buffers
~ smasenga@mu.ac.zm

Introduction to Biochemistry
•Biochemistry is the study of chemical and biological
substances and processes in living organisms
throughout the span of life.
•Structure, property, function, processes (metabolism)
•Normal biochemical processes are the basis of health
and disease
~ smasenga@mu.ac.zm

~ smasenga@mu.ac.zm

Water
•Predominant chemical component of living organisms
•Excellent nucleophile, reactant or product in many
metabolic reactions.
•The water molecule has tetrahedral geometry, Water
Forms Hydrogen Bonds
~ smasenga@mu.ac.zm
Hydrogen bonding
influences the
physical properties –
high viscosity,
surface tension, and
boiling point and pH

Water, H2O
•Interaction with water influences the structure of
biomolecules
•A covalent bond - sharing of electron pairs between
atoms forming stable balance of attractive and
repulsive forces between atoms
•All the major components in cells (proteins, DNA and
polysaccharides) are also dissolved in water.
~ smasenga@mu.ac.zm

Water, H2O
•Water Molecules Exhibit a Slight but Important
Tendency to Dissociate releasing O2 and H+
• pH = -log[H+]
• Low pH values correspond to high concentrations of H+
• and high pH values correspond to low concentrations of
H+
•Hydrogen ions are produced in the body as a result of
metabolism to create acidic or alkaline concentrations
• Substance that dissociates to produce H+ forms acids
• Substance that accepts H+ ions, produce a base, alkaline
~ smasenga@mu.ac.zm

Acids and bases
•Acid
• HA ↔ H+ + A- e.g., Phosphoric acid
• H3PO4 ↔ H+ + H2PO4
-
•Base
• Sodium hydroxide
• NaOH + H+ ↔ Na++ H2O
•The strength of an acid is measured by its dissociation
constant K
~ smasenga@mu.ac.zm

Dissociation constant
•Example:
• HA ↔ H+ + A-
• For a strong acid, K is large (> 1) and pK is small (< 0)
• For a weak acid, K is small (< 10-3) and pK is large (> 3)
~ smasenga@mu.ac.zm
AND

Hydrogen and pH
•Blood hydrogen ion normal concentration [H+]) is 35
- 45 nmol/l.
•Concentrations below 20 nmol/l or above 120 nmol/l
are generally incompatible with life.
•The concentration is better expressed as pH
~ smasenga@mu.ac.zm

Sources of hydrogen
•oxidation of proteins, nucleic acids and phospholipids
produces phosphoric and sulphuric acids
•incomplete (anaerobic) metabolism of fat and
carbohydrates produces organic acids such as lactic,
acetoacetic and β-hydroxybutyric acids
•Normal metabolic processes - gluconeogenesis and
oxidation of ketones remove the bulk of the hydrogen
ions produced
•50 - 100 mmoles of hydrogen ions excess produced
per day – Removed by Kidney
~ smasenga@mu.ac.zm

Sources of hydrogen
•Complete (aerobic) metabolism of fat and
carbohydrates produces CO2 - forms a weak acid
(carbonic acid)
• transported to the lungs in the blood and is rapidly excreted
by the lungs
~ smasenga@mu.ac.zm

Physiological buffers
• A buffer is a solution containing a conjugate acid-base
pair, made up of a weak acid and its salt, which minimises
changes in pH
• Salt = An ionic compound, where the positive ion (cation)
is anything except H+ , and the negative ion (anion) is
anything except OH- . Salts dissociate completely in water.
• The body contains a number of buffers that bind H+:
• Proteins: haemoglobin has a high capacity for binding hydrogen
ions.
~ smasenga@mu.ac.zm

• Buffers bind or release hydrogen ions depending on the
surrounding hydrogen ion concentration, by shifting the
equilibrium of the reaction
• in presence of excess H+ equilibrium shifts towards acid, excess
free H+ removed
• in presence of deficient H+ equilibrium shifts towards base
deficient free H+ replaced
• Buffers thus minimize changes in free hydrogen ion
concentration, and thus minimize changes in pH.
Buffering is however only a short-term solution - any
excess hydrogen ions must eventually be excreted from the
body.
~ smasenga@mu.ac.zm

• the most important buffer system is however the
bicarbonate system
•
•Features:
• H2CO3 dissociates to H2O and CO2
• HCO3 is retained and regenerated by the kidneys.
~ smasenga@mu.ac.zm

Role of haemoglobin - transport of CO2 and
buffering
~ smasenga@mu.ac.zm

Normal ranges
•pH 7.35 - 7.45
•pCO2 4.5 - 6.1 kPa
•[HCO3-] 22 - 26 mmol/l
~ smasenga@mu.ac.zm

Disease due to poor acid/base balance
•Metabolic acidosis - decrease in the blood pH caused
by a decrease in the bicarbonate concentration.
• Due to loss of bicarbonate, or accumulation of hydrogen
•Common causes of metabolic acidosis
1. Diarrhoea - Stool water contains high
concentrations of potassium and bicarbonate
• In acute diarrhoea main losses are of water, sodium and
bicarbonate
• the main losses are of potassium and bicarbonate
~ smasenga@mu.ac.zm

2. Diabetic ketoacidosis (DKA)
~ smasenga@mu.ac.zm

3. Lactic acidosis
~ smasenga@mu.ac.zm
4. Chronic renal failure – H+ not excreted

Clinical effects of Acidosis
•Increased [H+] stimulates the respiratory center and
causes hyperventilation.
• deep, rapid and gasping respiration known as Kussmaul
breathing.
• This is a physiological compensatory response which
decreases the pCO2 and therefore returns the pH towards
normal.
•Increased [H+] commonly causes hyperkalaemia.
• excess hydrogen ions move into cells, displacing potassium
ions.
• risk of cardiac arrhythmias, especially in the presence of
hyperkalaemia.
~ smasenga@mu.ac.zm

Clinical effects of Acidosis
•Increased [H+] depresses consciousness, which
can progress to coma and death.
~ smasenga@mu.ac.zm

Treatment of metabolic acidosis
•1. Treat the primary cause.
•2. Treat any dehydration and hyperkalaemia which are
commonly present.
•3. Treat the acidosis if severe (pH < 7.0) by
administering NaHCO3
~ smasenga@mu.ac.zm

Beware of the following dangers in correcting
acidosis by administering HCO3
•Should not be done too fast, The brain may become
more acidotic than before.
• As soon as bicarbonate is administered it increases the blood
pH. This switches off the stimulus for hyperventilation and
the pCO2 increases.
• The higher pCO2 equilibrates across the blood-brain-barrier
faster than the higher [HCO3-], thereby dropping the pH of
the brain.
•Hyperkalaemia may change to dangerous
hypokalaemia
~ smasenga@mu.ac.zm

Metabolic alkalosis
•there is an increase in the blood pH caused by an
increase in the bicarbonate concentration.
• Due to the gain of bicarbonate, or the loss of hydrogen
ions.
•Common causes of metabolic alkalosis
1. Vomiting - A good biochemical clue to identifying
vomiting as the cause of a metabolic alkalosis, is that the
urine chloride concentration is < 5 mmol/l.
2. nasogastric suction
~ smasenga@mu.ac.zm

Common causes of metabolic alkalosis
•Renal loss
•a) diuretics
•b) excess mineralocorticoid action
•c) potassium depletion due to many causes,
including purgatives
•Clinical effects of alkalosis
•Hypokalaemia
•Tetany: involuntary contraction of muscles,
~ smasenga@mu.ac.zm

Treatment of metabolic alkalosis
•1. Treat the primary cause.
•2. Treat any dehydration and hypochloraemia which
are present with normal saline (NaCl).
•3. Treat any hypokalaemia present with KCl
~ smasenga@mu.ac.zm

RESPIRATORY ACIDOSIS
• there is always an increase in the pCO2 (hypercapnia), and
a decrease in the pO2 (hypoxia). Acute or chronic
• The primary problem alveolar hypoventilation, which can
be caused by:
• the respiratory rate (controlled by the respiratory
centre)
• the integrity of the chest wall
• the patency of the airways
• the integrity of the lung tissue
~ smasenga@mu.ac.zm

CAUSES OF RESPIRATORY ACIDOSIS
•Depression of respiratory centre
• Drugs such as morphine, barbiturates, alcohol or general
anaesthetics
• Head injury
• Intracerebral disease or tumours
•Physical inability to ventilate
• Crush injury to chest, flail chest
• Muscle paralysis, muscle relaxants
~ smasenga@mu.ac.zm

CAUSES OF RESPIRATORY ACIDOSIS
•Airway obstruction
• Asthma
• Chronic obstructive airways disease (COAD) - emphysema
and chronic bronchitis
• Foreign body inhalation
•Pulmonary disease causing decreased CO2 and O2
exchange
• Severe pneumonia
• Severe lung collapse
• Severe pulmonary fibrosis
~ smasenga@mu.ac.zm

Treatment of respiratory acidosis
•Treat the underlying cause, e.g., remove any physical
airway obstruction
•Improve alveolar ventilation and lower the pCO2 by
using physiotherapy, bronchodilators, antibiotics and
assisted ventilation if necessary.
•Improve the hypoxia
~ smasenga@mu.ac.zm

Respiratory alkalosis
•In a respiratory alkalosis there is always a decrease in
the pCO2 (hypocapnia), but hypoxia is not invariably
present.
•The primary problem in any case of respiratory
alkalosis is respiratory hyperstimulation, when the rate
of excretion of CO2 exceeds the rate of production
of CO2.
~ smasenga@mu.ac.zm

Causes of respiratory alkalosis
•Direct stimulation of respiratory centre
• i) Drugs e.g., salicylates
• ii) Anxiety, hysteria
• iii) Brain stem disease
•Mechanical overventilation
•Hypoxia
• High altitude
• Anaemia
• Pulmonary disease causing decreased O2 diffusion
• Pulmonary oedema
~ smasenga@mu.ac.zm

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1.0 Biophysical Chemistry.pdf 12323323w46