08 May 2016

Lecture #1: Introduction to General Pathology


 Pathology is the study of disease by scientific methods. The word pathology came from the Latin words “patho” and “logy.” “Patho” means disease and “logy” means study, therefore pathology is a scientific study of disease. Disease may, in turn, be defined as an abnormal variation in structure or function of any part of the body. Pathology gives explanations of a disease by studying the following four aspects of the disease:

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.

B.     Pathogenesis

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.

 Diagnostic Techniques used in Pathology:
 
a.      Histopathology

b.      Cytopathology

c.       Hematopathology

d.      Immunohistochemistry

e.       Microbiological Examination

f.        Biochemical examination

g.       Cytogenetics

h.      Molecular Techniques

i.         Autopsy

A.     Histopathologic Techniques

 Histopathologic examination studies tissues under the microscope. During this study, the pathologist looks for abnormal structures in the tissue.

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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