a.
Etiology
b.
Pathogenesis
c.
Morphologic Changes
d.
Functional derangements and Clinical
Significance
A.
Etiology
Etiology of a disease means the
cause of the disease. If the cause of a disease is known, it is called primary
etiology. If the cause of the disease is unknown, it is called idiopathic. Knowledge
or discovery of the primary cause remains the backbone on which a diagnosis can
be made, a disease is understood and a treatment developed. There are two major classes of etiologic
factors: Genetic and Acquired.
Pathogenesis
means the mechanism through which the cause operates to produce the
pathological and clinical manifestations. The pathogenetic mechanisms could
take place in the latent or incubation period. Pathogenesis leads to
morphologic changes.
C.
Morphologic Changes
The morphologic changes refer to
the structural alterations in cells or tissues that occur following the
pathogenetic mechanisms. The structural changes in the organ can be seen within
the naked eye or they may only be seen under the microscope. Those changes that
can be seen with the naked eye are called gross morphologic changes and those
that are seen under the microscope are called microscopic changes. Both the
gross and the microscopic morphologic changes may only be seen in that disease,
i.e., they may be specific to that disease. Therefore, such morphologic changes
can be used by the Pathologist to identify (i.e., to diagnose) the disease. In addition,
the morphologic changes will lead to functional alteration and to the clinical
signs and symptoms of the disease.
D.
Functional derangements and
Clinical Significance
The morphologic changes in the
organ influence the normal function of the organ. By doing so, they determine
the clinical features (symptoms and signs), course and prognosis of the
disease.
a.
Histopathology
b.
Cytopathology
c.
Hematopathology
d.
Immunohistochemistry
e.
Microbiological Examination
f.
Biochemical examination
g.
Cytogenetics
h.
Molecular Techniques
i.
Autopsy
A.
Histopathologic Techniques
Tissues for histopathological
examination are obtained by biopsy. Biopsy is a tissue sample from a living
person to identify the disease. Biopsy can either be incisional or excisional. The
opposite of biopsy is autopsy.
Excisional biopsy is when an
entire lump or suspicious area is removed. Incisional biopsy or core biopsy is
when only a sample of tissue is removed with preservation of the histological
architecture of the tissue’s cells.
Once the tissue is removed from
the patient, it has to be immediately fixed by putting it into adequate amount
of 10% Formaldehyde (10% Formalin) before sending it to the Pathologist. The purpose
of fixation is:
a.
To prevent autolysis and bacterial
decomposition and putrefaction
b.
To coagulate the tissue to prevent loss of
easily diffusible substances
c.
To fortify the tissue against the deleterious
effects of the various stages in the preparation of sections and tissue
processing.
d.
To leave the tissues in a condition which
facilitates differential staining with dyes and other reagents.
Once the tissue arrives at the
Pathology Department, the Pathologist will exam it macroscopically (i.e. naked
eye examination of the tissues)
Then the tissue is processed to
make it ready for microscopic examination. The whole purpose of the tissue
processing is to prepare a very this tissue (i.e. five to seven µm or one cell
thick tissue) which can be clearly seen under the microscope. The tissue is
processed by putting it into different chemicals. It is then impregnated
(embedded) in paraffin, sectioned (cut) into thin slices and is finally
stained.
The stains can be Hematoxylin /
Eosin dye or other special stain depending on the tissue sample.
B.
Cytopathology
Cytopathology
is the study of cells from various body sites to determine the cause or nature
of disease.
Applications
of cytopathology:
a.
Screening for the early detection
of asymptomatic cancer
b.
Diagnosis of symptomatic cancer
c.
Surveillance of patients treated
for cancer
Different
cytopathologic methods:
a.
Fine needle
aspiration cytology (FNAC)
In FNAC,
cells are obtained by aspirating the diseased organ using a very thin needle under
negative pressure. Virtually any organ or tissue can be samples by fine needle
aspiration. The aspirated cells are then stained and are studied under the
microscope. Superficial organs (e.g. thyroid, breast, lymph nodes, skin and
soft tissues) can easily be aspirated. Deep organs, such as lung, mediastinum,
liver, pancreas, kidneys, adrenal gland, and retroperitoneum are aspirated with
guidance by fluoroscopy, ultrasound, or CT Scan. FNAC is cheap, fast and
accurate in diagnosing many diseases.
b.
Exfoliative
Cytology
Refers to
the examination of cells that are shed spontaneously into body fluids or
secretions like sputum, cerebrospinal fluid, urine, effusions in body cavities
(pleura, pericardium, peritoneum), nipple discharge and vaginal discharge.
c.
Abrasive
Cytology
Cells are
obtained directly from the surface of the target of interest which can be done
by scraping, brushing or washing. Samples can be obtained from superficial or
deep lesions.
Examples:
Cervical scrappings, endoscopy, gastric lavage
C.
Hematological examination
This is a method by which abnormalities
of the cells of the blood and their precursors in the bone marrow are
investigated to diagnose the different kinds of anemia or leukemia.
D.
Immunohistochemistry
Immunohistochemistry (IHC) refers
to the process of detecting antigens in cells of a tissue section by exploiting
the principle of antibodies binding specifically to antigens in biological
tissues.
E.
Microbiological Examination
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F.
Biochemical Examination
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G.
Clinical Genetics (Cytogenetics)
This is a method in which
inherited chromosomal abnormalities in the germ cells or acquired chromosomal
abnormalities in somatic cells are investigated using the techniques of
molecular biology.
H.
Molecular Techniques
Molecular
Pathology focused on the study and diagnosis of diseases through the
examination of molecules within organs, tissues or body fluids.
Molecular
Pathology is commonly used in diagnosis of cancer and infectious diseases. Techniques
are numerous but include quantitative polymerase chain reaction (qPCR),
multiplex PCR, DNA microarray, in situ hybridization, DNA sequencing, antibody
based immunofluorescence tissue assays, molecular profiling of pathogens, and
analysis of bacterial genes for antimicrobial resistance.
I.
Autopsy
Autopsy is examination of the
dead body to identify the cause of death.
Causes of Disease
Diseases can be caused by either environmental, genetic or
combination of environmental or genetic factors.
A.
Environmental Factors
a.
Physical agents
These include trauma, radiation,
extremes of temperatures and electric power. These agents apply excess physical
energy, in any form, to the body.
b.
Chemicals
With the use of an ever–increasing number of chemical agents such
as drugs, in industrial processes, and at home, chemically induced injury has
become very common. Their effects vary:
1. Some act in
a general manner, for example cyanide to all cells.
2. Others act
locally at the site of application, for example strong acids and caustics
3. Another group
exhibits a predilection for certain organs, for example – the effect of
paracetamol and alcohol on liver. Many toxic chemicals are metabolized in liver
and excreted in kidney; as a result, these organs are susceptible to chemical
injury.
c.
Nutritional deficiencies and
excesses
Nutritional deficiencies may
arise as a result of poor supply, interference with absorption, inefficient
transport within the body, or defective utilization. It may take the form of
deficiency either of major classes of food, usually protein and energy or
vitamins or elements essential for specific metabolic processes, e.g. iron for
hemoglobin production. Often, the deficiencies are multiple and complex.
On the other hand, dietary excess
plays an important role in diseases in Western countries. Obesity has become
increasingly common, with its attendant dangers of type 2 diabetes, high blood
pressure and heart disease.
d.
Infections and infestations
Viruses, bacteria, fungi, protozoa and metazoa all cause diseases.
They may do so by causing cell destruction directly as in virus infections (for
example poliomyelitis) or protozoal infections (for example malaria). However,
in others the damage is done by toxins elaborated by the infecting agent as in diphtheria
and tetanus. Like chemicals, they may have a general effect of they may show a
predilection for certain tissues.
e.
Immunological factors
The immune process is essential
for protection against micro – organisms and parasites. However, the immune
system can be abnormal which can lead to diseases. The abnormalities of the
immune system include:
1.
Hypersensitivity reaction
This is exaggerated immune
response to an antigen. For example, bronchial asthma can occur due to
exaggerated immune response to the harmless pollen.
2.
Immunodeficiency
This is due to deficiency of a
component of the immune system which leads to increased susceptibility to different
diseases. An example is AIDS.
3.
Autoimmunity
This is an abnormal (exaggerated)
immune reaction against the self–antigens of the host. Therefore, autoimmunity is
a hypersensitivity reaction against the self–antigens. For example, Type I
Diabetes Mellitus is caused by autoimmune destruction of the beta cells of the
Islets of Langerhans of the pancreas.
f.
Psychogenic factors
The mental stresses imposed by
conditions of life, particularly in technologically advanced communities, are
probably contributory in some group of diseases.
B.
Genetic Factors
These are hereditary factors that
are inherited genetically from parents.
Course of Disease
The course of a disease in the absence of any intervention is
called the natural history of the disease. The different stages in the natural
history of disease include:
a.
Exposure to various risk factors (causative
agents)
b.
Latency, period between exposure and
biological onset of disease.
c.
Biological onset of disease; this marks the
initiation of the disease process, however, without any sign or symptom. Following
biological onset of disease, it may remain asymptomatic or subclinical (i.e.
without any clinical manifestations), or may lead to overt clinical disease.
d.
Incubation (induction) period refers to
variable period of time without any obvious signs or symptoms from the time of
exposure.
e.
The clinical onset of the disease, when the
signs and symptoms of the disease become apparent. The expression of the disease
may be variable in severity or in terms of range of manifestations. Following
clinical onset, disease may follow any of the following trends:
(1) Resolution
can occur leaving no sequelae
(2) The disease
can settle down, but sequelae are left
Sequelae are a pathological
condition resulting from a disease, injury, therapy or other trauma. Typically,
sequelae are chronic condition that is a complication which follows a more acute
condition. It is different from, but is a consequence of, the first condition. Timewise,
a sequelae contrasts with a late effect, where there is a period, sometimes as
long as several decades, between the resolution of the initial condition and
the appearance of the late effect.
Example: Rheumatic fever is a non–suppurative
sequela of a primary infection of group A Streptococcus bacteria.
(3) It may
result in death
f.
The onset of permanent damage
g.
Death
Clinical death is the reversible transmission
between life and biologic death. Clinical death is defined as the period of
respiratory, circulator and brain arrest during which initiation of resuscitation
can lead to recovery.
Clinical death begins with either
the last agonal inhalation or the last cardiac contraction.
Signs indicating clinical death
are:
(1) The patient
is without pulse of blood pressure and is completely unresponsive to the most
painful stimulus.
(2) The pupils
are widely dilated
(3) Some reflex
reactions to external stimulations are preserved. For example, during
intubations, respiration may be restored in response to stimulation of the
receptors of the superior laryngeal nerve, the nucleus of which is located in
the medulla oblongata near the respiratory center.
(4) Recovery can
occur with resuscitation.
Biological Death (sure sign of death), which sets
in after clinical death, is an irreversible state of cellular destruction. It manifests
with irreversible cessation of circulatory and respiratory functions, or
irreversible cessation of all functions of the entire brain, including brain
stem.
However, one should notice that
there internationally accepted criteria to diagnose biological death.
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