Biochem2.pptx

CHAPTER TWO
Water, Acid, base, and Buffers

Water
Water is a major chemical component of the earth’s
surface.
It is a cradle(origin) molecule of life.
Cellular world is an aqueous world.
Normal metabolic activity can occur only when cells have
sufficient amount of water
Water is the most abundant substance in living system that
makes up 70 % or more of the total weight of most
organisms
2
2/3/2023 Biochemistry for PC-1 , AMU

Functions of Water in the living cells
1. Water is a solvent for many ionic and neutral compounds.
2. Water is involved in metabolism. eg. digestion /hydrolysis, energy
metabolism, formation of biopolymers (condensation reaction)…
3. Water is important to maintain the structure and functions of
macromolecules of cells. E.g. Proteins, lipids…
4. Regulation of body temperature by evaporating the moisture in
the lung and from the skin/thermoregulation.
5. Water is the main constituent of all body fluids.
6. Removal of waste materials from the body
2/3/2023 Biochemistry for PC-1 , AMU 3

Distribution of water in the body
• Nearly 45L of water is present in 70 Kg adult male.
 30L is found in intra cellular fluids including bone
 15L is present in extracellular fluids

Water…
• Since fat is water insoluble, water content of body alters
according to fat present in the body.
 In obese people water constitutes low percentage (55-
65%) of body weight.
 In lean people water constitutes high percentage (70-
75%) of body weight.
 Females have low water percentage (65%) because of
relatively high percentage of fat compared to males.

Water…
 The daily water intake and water output of an adult leading
sedentary life is given below

Factors affecting water intake and water output
1. Environment influences water intake and water output of an
individual.
 In hot weather water output decreases (urine) and water
intake increases.
 Water intake is less in cold climate and water output (urine)
is more.
2. In disease like diabetes, output of urine is more.

Maintenance of water balance
• Fluid intake (thirst) and urine volume are involved in water
balance maintenance.
 They play crucial role in body water homeostasis.

Disorders of water balance
1. Dehydration (water depletion): It is due to deficiency of water.
 It occurs in vomitting, diarrhoea, diabetes incipidus and in lesions
of hypothalamus.
2. Over hydration (Edema): It is due to excess water in body. It may
leads to edema.
• It occurs in water intoxication, excessive administration of
intravenous fluids, increased secretion of ADH, protein deficiency,
cancer and drugs.

Structure and chemical properties of H2O
2/3/2023 10
 Water is highly polar because of its bent geometry.
 Water is highly cohesive because of intermolecular hydrogen
bonding.
 Water participates in H-bonding with biomolecules
 Water is the universal medium and makes up the matrix of all
the biological fluids.
 Water interacts with most of the biomolecules and the
interaction many times results in ionization of water to give
rise to H+ and OH- Ions.
 A solution is considered neutral if it carries equal
concentration of hydrogen and hydroxyl ions.

2/3/2023 11
 For water to be liquid at room temperature, and also to be
formed as crystalline water (ice), which is favored by the
extreme ordering of molecule, the hydrogen bonds between the
water molecules plays important role.
 hydrogen bond: it is an electrostatic attraction results
between the Oxygen atom of one water molecule and the
Hydrogen of another
 Hydrogen bonding gives water its unusual properties

Figure : Intermolecular forces exist between water molecules. Bonds
exist within molecules.
2/3/2023 12

 Unusual Properties
 In comparison with chemical compounds of similar atomic
organization and molecular size (like NH3,CH4..), water
displays unexpected properties.
Higher boiling point
High melting point
High heat of vaporization
High surface tension
High dielectric constant
 Solvent Properties
Because of its highly polar nature, water is an excellent
solvent for ionic substances such as salts.
13

Acids, bases and pH
Acids are compounds that donate a hydrogen ion to a
solution and that lowers the pH
Bases are compounds that accept hydrogen ions and that
raises the pH.
pH is the negative logarithm of hydrogen ion
concentration [H+].
i.e. pH= - log [H+]
The most important factor ,which must be considered in the
regulation of acid base balance is the hydrogen ion
concentration.

16

pH of Some Common
Liquids

18
The body produces more acids than bases
Acids take in with foods
Acids produced by metabolism of carbohydrates, lipids ,
proteins and nucleotides.
Cellular metabolism produces CO2
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3
-
Carbonic anhydrase catalyze the formation of carbonic
acid from carbon dioxide and water in RBCs and lung.

Fig. Formation of CO2
19

Carbonic acid formation and dissociation
In RBCs one of the fate of
carbon dioxide is to form
carbonic acid which is
catalyzed by carbonic
anhydrase. The reverse
reaction take place in the
lung where the carbon
dioxide is released into the
expired air.

Effects of metabolism on pH
During metabolism, the body produces a number of acids that
increase the hydrogen ion concentration of the blood or other body
fluids and tend to lower the pH .
These metabolically important acids can be classified as weak acids
or strong acids by their degree of dissociation into a hydrogen ion
and a base (the anion component).
Inorganic acids such as sulfuric acid (H2SO4) and hydrochloric acid
(HCl) are strong acids that dissociate completely in solution .
Organic acids containing carboxylic acid groups (e.g., lactic acids, the
ketone bodies, acetoacetic acid and β-hydroxybutyric acid) are weak
acids that dissociate only to a limited extent in water.
The removal of excess H+ can be achieved by buffers system.

Acids in the blood of healthy individuals
22

Volatile acids : The volatile acids are produced within our body as a result of
carbohydrate or fat metabolism. The metabolic activities in the body produce CO2
and H2O. These two can combine to give rise to carbonic acid (H2CO3), a weak acid.
Carbonic acid can dissociate into H+ and HCO3
- ions.
 About 10000 to 15000 mM of carbonic acid is produced in an adult individual
daily.
 This much acid could be equivalent to 500 ml of concentrated HCl, which is an
enormous acid load.
Non-volatile acids or Fixed acids : In addition to the volatile acids, human body
also produces inorganic acids like sulfuric acid, phosphoric acid and organic acids
such as lactic acid, pyruvic acid, citric acid or other organic acids.
 They are produced from the metabolism of food components that contain sulfur
or phosphorus. They can also be produced by the incomplete metabolism of
carbohydrates or fats.
 Some fixed acids could be called iatrogenic in origin i.e. contributed by the
ionization or metabolism of drugs.
 The overall contribution of the fixed acid to total acid load in our body is
small compared to that of volatile acids.
Human body produces two types of acids

The normal pH of arterial blood is 7.4, whereas the pH of
venous blood and interstitial fluids is about 7.35 because of
the extra amounts of carbon dioxide (CO2) released from the
tissues to form H2CO3 in these fluids .
Because the normal pH of arterial blood is 7.4, a person is
considered to have acidosis when the pH falls below this value
and to have alkalosis when the pH rises above 7.4.
The lower limit of pH at which a person can live more than a
few hours is about 6.8, and the upper limit is about 8.0.
24

Intracellular pH usually is slightly lower than plasma pH
because the metabolism of the cells produces acid, especially
H2CO3.
Depending on the type of cells, the pH of intracellular fluid
has been estimated to range between 6.0 and 7.4.
Hypoxia of the tissues and poor blood flow to the tissues can
cause acid accumulation and decreased intracellular pH. In
the absence of oxygen, lactic acid is produced that lowers the
pH.
25

The pH of urine can range from 5 to 8.0, depending on the acid-base
status of the extracellular fluid. The wide range is because kidneys
play a major role in correcting abnormalities of extracellular fluid H+
concentration by excreting acids or bases at variable rates.
An extreme example of an acidic body fluid is the HCl secreted into
the stomach by the parietal cells of the stomach mucosa.
The H+ concentration in these cells is about 4 million times greater
than the hydrogen concentration in blood, with a pH of 0.8.
26

pH of different body fluids
27

Body acid-base imbalance
pH< 7.35 acidosis
pH > 7.45 alkalosis

Small changes in pH can produce major disturbances
Homeostasis of pH is
tightly controlled.
 Most enzymes function
only with narrow pH
ranges.
 Acid-base balance can
also affect electrolytes
(Na+, K+, Cl-).
 Can also affect
hormones.

Acid base balance or Hydrogen (H+) Homeostasis
 Medical and biological Importance
1. Proper pH is required for the optimal action of enzymes and
for the transport of molecules within the body and between
cells and its surroundings.
2. Proper pH is required for the maintenance of structure of
nucleic acids, proteins, coenzymes and various metabolites.
3. Acidosis and alkalosis are two important disorders of acid
base balance.

Hydrogen (H+) Homeostasis
 Three different systems are involved in the maintenance of
stable blood pH level. They are :
I. Buffer systems of blood plasma, tissue fluids and cells like
erythrocytes
II. Lungs
III. Kidneys
• By the combined action of these systems constant H+
concentration is maintained in the body.

Buffers
Buffers, by definition, are the solutions that resist the change in
pH upon addition of acid or base. The buffers could be formed in
two ways
a) by mixture of weak acids and their salts with strong base and
b) by mixture of weak alkali and its salt with strong acid.
 They are responsible for the maintenance of pH of plasma, ICF,
ECF and tissues of the body

Buffer system
Body defenses mechanism against changes in hydrogen ion
concentration.
There are three primary systems that regulate the H+
concentration in the body fluids to prevent acidosis or
alkalosis:
1. The chemical acid-base buffer systems of the body
fluids, which immediately combine with acid or base to
prevent excessive changes in H+ concentration.
When there is a change in H+ concentration, the chemical
buffer systems of the body fluids react within a fraction of
a second to minimize these changes (first line of
defense).
33

Chemical buffer systems do not eliminate H+ from or
add them to the body but only keep them tied up until
balance can be reestablished.
2. The respiratory center, which regulates the removal of
CO2 (and, therefore, H2CO3) from the extracellular
fluid.
3. The kidneys, which can excrete either acid or alkaline
urine, thereby readjusting the extracellular fluid H+
concentration toward normal during acidosis or alkalosis.

The second line of defense, the respiratory system, also acts
within a few minutes to eliminate CO2 and, therefore,
H2CO3 from the body.
These first two lines of defense keep the H+ concentration
from changing too much until the more slowly responding
third line of defense, the kidneys, can eliminate the excess
acid or base from the body.
Although the kidneys are relatively slow to respond
compared with the other defenses, over a period of hours to
several days, they are by far the most powerful of the
acid-base regulatory systems.
35

Body defense mechanism against pH shift

 Buffers of blood plasma
 Bicarbonate and Carbonic acid (HCO3–/H2CO3) buffer
• It is present in greater concentration and plays major role in
regulating pH of blood with in normal limits.
• Bicarbonate buffer acts against metabolic acids or nonvolatile
acids produced
1. Chemical buffer systems of the body

The carbonic acid – bicarbonate system is the major blood buffering system and
accounts for about 65% of the plasma buffering capacity. The buffer operates by
inter conversion of the two components, as shown
The bicarbonate buffer has another important reaction attached to it which makes it
extremely resilient to any changes in blood pH. This reaction is the
dissociation/association of carbonic acid to release/bind carbon dioxide which is
exhaled out into the atmosphere.
 Integration of the bicarbonate buffer with the atmospheric carbon dioxide makes it
an ‘open system’.
Bicarbonate and Carbonic acid (HCO3–/H2CO3) buffer
Carbonic
Anhydrase

Phosphate (H2PO–4/HPO42–) buffer and protein
buffer
• Their concentration is low in blood so they play
minor role in regulating blood pH.
• The phosphate buffer is more effective than
bicarbonate buffer
Phosphate buffer: major intracellular or cytosolic
buffer.

Protein Buffers
Includes hemoglobin in RBCs and other amino acids & proteins
that buffer in intracellular as well as extracellular fluids.
1. Carboxyl group gives up H+
2. Amino Group accepts H+
3. Side chains that can buffer are present on some amino acids
Properties of protein buffers
 Operate at maximum buffering capacity (pK=7.4)
 Found in high concentration inside cells (3/4 of the chemical
buffer of the body)

Protein Buffer Systems
The intracellular as well as extracellular proteins can also contribute to the buffering
capacity of body fluids.
The proteins carry ionisable side chains on their amino acids which can give rise
to the protein anions (Pr-) and free protons. Similarly, the protein anions can absorb
H+ ions to take care of excess acidity.
Proteins act as base (Pr-) under acidic conditions and absorb the H+ ions released by
the acids; and Act as acids (Pr-H) under alkaline conditions releasing the protons to
neutralize the alkali.
Histidine is the most effective amino acid with a pKa of 6.0.
 Albumin has 16 histidine residues which help it to act as an effective buffer in
plasma.
 Protein buffer contributes about 4% of the plasma buffering capacity.
Pr-H Pr- + [H+]

Buffers of red blood cells
• Most important buffer in R.B.C. is hemoglobin buffer
system.
• It is the major buffer system of blood as well as
erythrocytes.
• Hb buffer system is effective at body pH. Further high
Hb concentration (14 gm/dL) makes it major buffer
of blood.

2. Respiratory mechanisms of acid-base regulation
Exhalation of carbon dioxide
Quickest way to respond, takes minutes to
hours to correct pH
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

3. Kidney excretion of acid and base
Can eliminate large amounts of
acids.
Can also excrete base
Can conserve and produce
bicarbonate ions
Most effective regulator of pH
If kidneys fail, pH balance fails

Summary of maintenance of body pH
The body produces approximately
13 to 22 moles of acid per day
from normal metabolism.
The body protects itself against
this acidity by buffers that
maintain a neutral pH and by the
expiration of CO2 through the
lungs and the excretion of NH4+
and other ions through the kidney.

Disturbances in Acid base balance
• They are grouped into acidosis and alkalosis.
• Acidosis. It is due to accumulation of acids and
blood pH is below 7.4.
• Alkalosis. It is due to accumulation of alkali and
blood pH is above 7.4.

• Acidosis or alkalosis due to less or more of
bicarbonate are called as metabolic acidosis
or metabolic alkalosis respectively.
• Like wise acidosis or alkalosis due to more or less of
carbonic acid are called as respiratory acidosis and
respiratory alkalosis respectively.

 Metabolic acidosis. It is the most common acid base
disturbance.
• In this condition the plasma bicarbonate level is low.
• Decreased bicarbonate concentration because due
to over production of acids
Acidosis ( acidemia): pH < 7.35

Metabolic acidosis may result from
 Excess production of acids which occurs in diabetes
mellitus, starvation, phenyl ketonuria and maple syrup
urine disease.
 Intense muscular exercise may lead to accumulation of
lactic acid then the condition is called lactic acidosis
 Ingestion of mineral acids. Excessive administration of
certain drugs.
 Loss of HCO–3. It occurs in vomitting, diarrhoea, loss of
pancreatic fluids or upper intestinal contents due to
intestinal obstruction

• Decreased H+ secretion in kidney. It occurs in nephritis.
• Increased elimination of H CO–3 by kidney. It occurs in
renal failure

 Metabolic acidosis is compensated by lungs and
kidney.
 Increased respiration elminates CO2 faster and
carbonic acid content diminishes.
 The renal compensatory mechanism involves
excretion of more ammonia and acid phosphates.
• These compensatory mechanisms may restore pH of
blood.
 If acidosis is not compensated the pH falls and
patient may go into coma.
 Chronic metabolic acidosis cases are treated by
administration of sodium lactate or citrate.

 Metabolic alkalosis. It is rare. It is due to more
bicarbonate in plasma.
• Causes for metabolic alkalosis
 Excessive loss of HCl due to prolonged vomiting. It
occurs in pyloric obstruction.
 Ingestion of salts of acids like sodium lactate or
citrate and sodium bicarbonate.
 Excessive production and excretion of ammonia.
Alkalosis(alkalemia) pH >7.45

• This condition is compensated by pulmonary and renal
mechanisms.
• Pulmonary compensatory mechanism is hypoventilation.
Respiratory rate is decreased CO2 accumulates in plasma and
carbonic acid formation increases.
• At the same time kidney compensates alkalosis by increasing
elimination of H CO–3 and decreasing H+ secretion.
• By the combined action of these organs the blood pH come
back to normal.
• If metabolic alkalosis is not compensated, tetany develops and
convulsive seizures may occur in children

 Respiratory acidosis.
• It is due to more plasma PCO2 level.
Increased [CO2] that leads to increased [H2CO3].
Caused by increased retention of CO2 in the lung or
inhalation of ↑[CO2
Acidosis ( acidemia): pH < 7.35

Causes for respiratory acidosis
• Depression of respiration (Hypoventilation). Hypoventilation
occurs due to excessive dosage of morphine, barbiturates and
other respiratory depressents.
• Obstruction to air passage. It occurs in pneumonia,
emphysema, asthma and tracheal obstruction.
• Mainly renal mechanism compensate this condition by
absorbing more HCO–3 and eliminating more H+ and
ammonia in urine.

 Respiratory alkalosis.
• Plasma PCO2 level is low in this acid base imbalance
• Decrease blood CO2 tension due to hyperventilation.
Alkalosis(alkalemia) pH >7.45

Respiratory alkalosis may result from
• Hyperventilation. Stimulation of respiratory centre
in the brain leads to hyperventilation.
• It occurs in fever, head injury, anxiety, hysteria,
salicylate poisoning, hot climate and high altitude.
• Kidney compensates this imbalance by elimination of
more HCO–3 and decreasing H+ secretion

Laboratory diagnosis of acid base disturbances.
• Determination of the type of acidosis or alkalosis can be
made by measuring plasma pH, PCO2 and HCO–3.
• Various blood parameters in acid base disturbances are given
bleow :

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