CHEMICAL, PHYSICAL, AND BIOLOGICAL AGENTS
CHEMICAL AGENTS
TYPES OF AETIOLOGY
GENERAL OVERVIEW
The general pathology is the study of the causes (i. e. aetiology) and mechanisms (i. e. pathogenesis)
of disease. The causes of a disease can be of two types, which are:
• Endogenous aetiology: it is
related to cellular, or molecular
problems that are created by the
organism itself; an example is
the sickle cell anaemia, in which
the glutamate is substituted by
the valine in the -subunit of the
haemoglobin; this mutation has
a significant impact on the
erythrocytes and on their oxygen
transportation; in this disease
erythrocytes tend to aggregate, thereby creating thrombi, which are eventually removed
(anaemia); nowadays there is a gene therapy through which the correct gene for the -subunit
is placed on the haematopoietic stem cells; however this procedure is highly expensive, and
therefore not available to everyone.
• Exogenous aetiology: it is related to external factors, which causes
the disease; an example is the cervical carcinoma; this type of
cancer is caused mostly by human papillomavirus (HPV) infection;
there are also other factors that may influence the development of
the tumour, although they remain not clear.
The knowledge of the aetiology and pathogenesis of a disease permits the
development of prophylactic measures (i. e. prevention), diagnosis, and
therapy. Moreover, the cause of a disease can be either single or multifactorial.
There are two main types of prevention, which are:
• Primary prevention: it avoids the disease development by removing risk factors and causes;
examples are vaccination, lifestyle (e. g. smoking, nutritions, etc.), and protective measures
(e. g. against radiation).
• Secondary prevention: it modifies the disease outcome to permit a cure; examples are an
early diagnosis, mass screening (e. g. mammography for early diagnosis of breast cancer), and
screening of population at risk (e. g. patient with cancer family history).
EXOGENOUS AETIOLOGY
The exogenous causes of a disease derive from the environment, and they can be divided into three
types, which are:
• Physical agents: they are
physical factors, such as
radiation, UV light, mechanical
trauma, and temperature.
• Chemical agents: they are
chemical compounds, such as
acids, bases, solvents, metals,
and detergents.
• Biological agents: they are
products that derive from
, biological entities; examples are pathogens and bacterial toxins.
As regards, the endogenous causes, they are determined by alterations in the genome cause (i. e.
genetic and hereditary diseases).
The chemical agents are exogenous causes that can derive from different sources, which are
environment (e. g. natural, nutritional, etc.), derived from organism metabolism (e. g. activation
reactions, detoxification reactions, etc.), and xenobiotics (e. g. pesticides, drugs, industrial
compounds, etc.)
The modality of entering in contact with chemical agents can be via the skin, mucosa, ingestion,
inhalation, injection, wound, bites, and stings. The type of damage that is created can be acute and
chronic effects, cytotoxic, mutagenic, carcinogenic, and teratogenic effect, and allergenic effects (e.
g. type IV hypersensitivity reactions, contact dermatitis).
DIFFUSE AND SELECTIVE DAMAGES
DIFFUES DAMAGE
The damage that is created by chemical agents can be of two types, the diffuse and the selective
damage. The former is a consequence of common properties of chemical agents, while the latter
occurs when chemical alter a specific cellular component, thus
causing either its inhibition or loss of function.
The diffuse damage is caused by chemicals which can cause
different changes, which are:
• pH modification: it is caused by acids and bases, which
may form heat and burns; the pathogenesis depends on
the type of chemical agents, which can be of two types;
they are:
Acids: they can induce autolytic processes in
moderate concentration, while in high concentration there is an induction of tissue
dehydration, protein denaturation, and coagulative necrosis; the coagulative
necrosis limits the spread of the damage (e. g. kidney or liver infarct); examples of
acids are the muriatic acid (HCl), and the sulfuric acid (H2SO4).
Bases: they saponify fats, solubilise proteins, and
attract water, thus resulting in liquefactive
necrosis; the liquid consistency of the damaged
tissue permits the penetration of the damaging
agent deep into tissues (e. g. using caustic soda
without gloves); examples are sodium hydroxide
(NaOH) and ammonia (NH3).
• Damage by solvents: they are substances that solubilise
cell components; they are furtherly divided into two types, which are:
Non-polar solvents: they are solvents that are hydrophobic; they cause a complete
membrane disorganisation and cell lysis; keratin resists to non-polar effect, thus
creating a protective effect; examples are chloroform and acetone.
Polar solvents: they are solvents that are hydrophilic, which can be water, methanol,
and dimethyl sulfoxide; with hypotonic solutions the water enters within the cells
(more concentrated), thus causing cell swelling and
damage to subcellular structures; the cell may lyse (i.
e. cytolysis); with hypertonic solutions the water exit
from the cell (less concentrated), and it will shrink (i.
e. crenation, e. g. erythrocytes in urine sample).
• Protein denaturation: it is the modification of the secondary,
tertiary, or quaternary structures of proteins, thus resulting
, in impaired protein function; denaturising agents can be pH variations, metal ions, salts, and
organic compounds (e. g. urea).
CHANGES CHEMICALS DAMAGES EXAMPLES
Tissue dehydration,
Hydrochloric acid,
Acids protein denaturation,
sulfuric acid
pH modification coagulative necrosis
Tissue hydration, Sodium hydroxide,
Base
liquefactive necrosis ammonia
Membrane
Non-polar solvents disorganisation, cell Chloroform, acetone
lysis
Cell swelling and
Damage by solvents
cytolysis in hypotonic
Methanol, dimethyl
Polar solvents solution, cell shrinkage
sulfoxide
and crenation in
hypertonic solutions
pH variation, metal
Loss of protein Metal ions, urea,
Protein denaturation ions, organic
structure and function acids, bases
compounds
SELECTIVE DAMAGE
The selective damages are chemical compounds that cause specific reaction with biologically relevant
substrates. They are typically intoxication and poisoning, which are respectively caused by toxins and
poisons.
An example of selective damage is produced by
the prussic acid (hydrogen cyanide, HCN). This is a
poison that rapidly causes death by inactivating
mitochondrial cytochrome oxidase (complex IV).
Since cell cannot produce ATP, it will die.
Another example is given by the carbon monoxide
(CO). This odourless gas has high affinity for haemoglobin, which is converted into
carboxyhaemoglobin (COHb). Since cells and tissues starved of O2, it will gradually lead to death. Note
that there are several reported deaths due to CO intoxication every year, particularly in the US.
The toxic effects of most compounds depend on the dosage; in 1538 Paracelsus stated that all
substances are poisonous, there is none that is not a poison; the right dose differentiates a pose from
a remedy. Effects of poisons can be reduced in some cases by antidotes.
TOXINS AND POISONS
The toxins and poisons are chemical agents that typically cause a selective damage. They can be
divided into two types, which are:
• Exogenous toxins and poisons: they are
produced by external factors, such as
biological (e. g. bacteria, plants, animals,
etc.), environmental (e. g. heavy
metals), industrial (e. g. pesticides),
drugs, and nutritional elements.
• Endogenous toxins and poisons: they
are produced by the organism; they can
be formed by the GI tract, by metabolic alterations (e. g. glycated haemoglobin in diabetes),
CHEMICAL AGENTS
TYPES OF AETIOLOGY
GENERAL OVERVIEW
The general pathology is the study of the causes (i. e. aetiology) and mechanisms (i. e. pathogenesis)
of disease. The causes of a disease can be of two types, which are:
• Endogenous aetiology: it is
related to cellular, or molecular
problems that are created by the
organism itself; an example is
the sickle cell anaemia, in which
the glutamate is substituted by
the valine in the -subunit of the
haemoglobin; this mutation has
a significant impact on the
erythrocytes and on their oxygen
transportation; in this disease
erythrocytes tend to aggregate, thereby creating thrombi, which are eventually removed
(anaemia); nowadays there is a gene therapy through which the correct gene for the -subunit
is placed on the haematopoietic stem cells; however this procedure is highly expensive, and
therefore not available to everyone.
• Exogenous aetiology: it is related to external factors, which causes
the disease; an example is the cervical carcinoma; this type of
cancer is caused mostly by human papillomavirus (HPV) infection;
there are also other factors that may influence the development of
the tumour, although they remain not clear.
The knowledge of the aetiology and pathogenesis of a disease permits the
development of prophylactic measures (i. e. prevention), diagnosis, and
therapy. Moreover, the cause of a disease can be either single or multifactorial.
There are two main types of prevention, which are:
• Primary prevention: it avoids the disease development by removing risk factors and causes;
examples are vaccination, lifestyle (e. g. smoking, nutritions, etc.), and protective measures
(e. g. against radiation).
• Secondary prevention: it modifies the disease outcome to permit a cure; examples are an
early diagnosis, mass screening (e. g. mammography for early diagnosis of breast cancer), and
screening of population at risk (e. g. patient with cancer family history).
EXOGENOUS AETIOLOGY
The exogenous causes of a disease derive from the environment, and they can be divided into three
types, which are:
• Physical agents: they are
physical factors, such as
radiation, UV light, mechanical
trauma, and temperature.
• Chemical agents: they are
chemical compounds, such as
acids, bases, solvents, metals,
and detergents.
• Biological agents: they are
products that derive from
, biological entities; examples are pathogens and bacterial toxins.
As regards, the endogenous causes, they are determined by alterations in the genome cause (i. e.
genetic and hereditary diseases).
The chemical agents are exogenous causes that can derive from different sources, which are
environment (e. g. natural, nutritional, etc.), derived from organism metabolism (e. g. activation
reactions, detoxification reactions, etc.), and xenobiotics (e. g. pesticides, drugs, industrial
compounds, etc.)
The modality of entering in contact with chemical agents can be via the skin, mucosa, ingestion,
inhalation, injection, wound, bites, and stings. The type of damage that is created can be acute and
chronic effects, cytotoxic, mutagenic, carcinogenic, and teratogenic effect, and allergenic effects (e.
g. type IV hypersensitivity reactions, contact dermatitis).
DIFFUSE AND SELECTIVE DAMAGES
DIFFUES DAMAGE
The damage that is created by chemical agents can be of two types, the diffuse and the selective
damage. The former is a consequence of common properties of chemical agents, while the latter
occurs when chemical alter a specific cellular component, thus
causing either its inhibition or loss of function.
The diffuse damage is caused by chemicals which can cause
different changes, which are:
• pH modification: it is caused by acids and bases, which
may form heat and burns; the pathogenesis depends on
the type of chemical agents, which can be of two types;
they are:
Acids: they can induce autolytic processes in
moderate concentration, while in high concentration there is an induction of tissue
dehydration, protein denaturation, and coagulative necrosis; the coagulative
necrosis limits the spread of the damage (e. g. kidney or liver infarct); examples of
acids are the muriatic acid (HCl), and the sulfuric acid (H2SO4).
Bases: they saponify fats, solubilise proteins, and
attract water, thus resulting in liquefactive
necrosis; the liquid consistency of the damaged
tissue permits the penetration of the damaging
agent deep into tissues (e. g. using caustic soda
without gloves); examples are sodium hydroxide
(NaOH) and ammonia (NH3).
• Damage by solvents: they are substances that solubilise
cell components; they are furtherly divided into two types, which are:
Non-polar solvents: they are solvents that are hydrophobic; they cause a complete
membrane disorganisation and cell lysis; keratin resists to non-polar effect, thus
creating a protective effect; examples are chloroform and acetone.
Polar solvents: they are solvents that are hydrophilic, which can be water, methanol,
and dimethyl sulfoxide; with hypotonic solutions the water enters within the cells
(more concentrated), thus causing cell swelling and
damage to subcellular structures; the cell may lyse (i.
e. cytolysis); with hypertonic solutions the water exit
from the cell (less concentrated), and it will shrink (i.
e. crenation, e. g. erythrocytes in urine sample).
• Protein denaturation: it is the modification of the secondary,
tertiary, or quaternary structures of proteins, thus resulting
, in impaired protein function; denaturising agents can be pH variations, metal ions, salts, and
organic compounds (e. g. urea).
CHANGES CHEMICALS DAMAGES EXAMPLES
Tissue dehydration,
Hydrochloric acid,
Acids protein denaturation,
sulfuric acid
pH modification coagulative necrosis
Tissue hydration, Sodium hydroxide,
Base
liquefactive necrosis ammonia
Membrane
Non-polar solvents disorganisation, cell Chloroform, acetone
lysis
Cell swelling and
Damage by solvents
cytolysis in hypotonic
Methanol, dimethyl
Polar solvents solution, cell shrinkage
sulfoxide
and crenation in
hypertonic solutions
pH variation, metal
Loss of protein Metal ions, urea,
Protein denaturation ions, organic
structure and function acids, bases
compounds
SELECTIVE DAMAGE
The selective damages are chemical compounds that cause specific reaction with biologically relevant
substrates. They are typically intoxication and poisoning, which are respectively caused by toxins and
poisons.
An example of selective damage is produced by
the prussic acid (hydrogen cyanide, HCN). This is a
poison that rapidly causes death by inactivating
mitochondrial cytochrome oxidase (complex IV).
Since cell cannot produce ATP, it will die.
Another example is given by the carbon monoxide
(CO). This odourless gas has high affinity for haemoglobin, which is converted into
carboxyhaemoglobin (COHb). Since cells and tissues starved of O2, it will gradually lead to death. Note
that there are several reported deaths due to CO intoxication every year, particularly in the US.
The toxic effects of most compounds depend on the dosage; in 1538 Paracelsus stated that all
substances are poisonous, there is none that is not a poison; the right dose differentiates a pose from
a remedy. Effects of poisons can be reduced in some cases by antidotes.
TOXINS AND POISONS
The toxins and poisons are chemical agents that typically cause a selective damage. They can be
divided into two types, which are:
• Exogenous toxins and poisons: they are
produced by external factors, such as
biological (e. g. bacteria, plants, animals,
etc.), environmental (e. g. heavy
metals), industrial (e. g. pesticides),
drugs, and nutritional elements.
• Endogenous toxins and poisons: they
are produced by the organism; they can
be formed by the GI tract, by metabolic alterations (e. g. glycated haemoglobin in diabetes),
