Yilkal (R1)

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Introduction to pathology
Pathology is literally the study (logos) of suffering (pathos)
• Pathology is devoted to the study of the structural, biochemical, and
functional changes in cells, tissues, and organs that underlie disease
• It is abridging discipline involving both basic sciences and clinical
sciences.

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• By the use of molecular, microbiologic, immunologic, and morphologic
techniques, pathology attempts to explain the whys and wherefores of the
signs and symptoms manifested by patients while providing a rational basis
for clinical care and therapy.
• Traditionally, the study of pathology is divided into general pathology and
special, or systemic, pathology.
• General pathology is concerned with the basic reactions of cells and tissues
to abnormal stimuli that underlie all diseases. (cell injury, inflammation,
edema, autoimmune diseases…)
• Systemic pathology examines the specific responses of specialized organs
and tissues to more or less well-defined stimuli.
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What is health
• WHO definition – a complete physical, social and mental well being,
not merely absence of illness.
• What is disease
The term disease broadly refers to any condition that impairs normal
function, and is therefore associated with dysfunction of normal
homeostasis.
Disease is abnormal variation in structure or function of any part of the
body.

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• Morbidity  (from Latin morbidus, meaning "sick, unhealthy") is a diseased
state, disability, or poor health due to any cause.

• A refractory disease is a disease that resists treatment

• Progressive disease is a disease whose typical natural course is the

worsening of the disease until death, serious debility, or organ failure occurs

Mortality -death

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Scope of pathology

Pathology gives explanations of a disease by studying the following four

aspects of the disease.
1. Etiology
2. Pathogenesis
3. Morphologic changes
4. Functional derangements and clinical significance

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Etiology
Environmental agents:
• Physical
• Chemical
• Nutritional both excess and deficiency
• Infections and infestations
• Immunological
• Psychological
• Genetic Factors:
• These are hereditary factors that are inherited genetically from parents.
• Multifactorial: DM,HTN, malignancy, atherosclerosis…
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• The idea that one etiologic agent is the cause of one disease
developed from the study of infections and inherited disorders caused
by single genes—is not applicable to the majority of diseases
• The relative contribution of inherited susceptibility and external
influences varies in different diseases.
1-One agent ->One disease-Malaria
2-Several agents->One disease-DM, cancer
3-One agent-> several disease-Smoking, alcohol, hypercholesterolemia

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Pathogenesis
• Pathogenesis refers to the sequence of events in the response of cells
or tissues to the etiologic agent, from the initial stimulus to the
ultimate expression of the disease.
• Depending on etiologic agent it varies
• It is the pathogenesis which results morphologic changes

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Morphologic changes:
• The morphologic changes refer to the structural alterations in cells or
tissues that are either characteristic of the disease or diagnostic of the
etiologic process.
• Those changes that can be seen with the naked eye are called gross
morphologic changes & those that are seen under the microscope are
called microscopic changes

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• Both the gross & the microscopic morphologic changes may only be
seen in that disease, i.e. they may be specific to that disease
(Pathognomonic).
• Therefore, such morphologic changes can be used by the pathologist
to identify (i.e. to diagnose) the disease
• Traditionally, the practice of diagnostic pathology has used
morphology to determine the nature of disease and to follow its
progression

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 Goiter, thyroidectomy specimen and microscopic appearance from left to right

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 RH cell Pathognomonic for classical HL
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Grossly-supra clavicular LAP Microscopically- H&E
Functional Derangements and Clinical
Manifestations.
The end results of genetic, biochemical, and structural changes in cells
and tissues are functional abnormalities, which lead to the clinical
manifestations (symptoms and signs) of disease, as well as its
progress (clinical course and outcome).
Hence, clinicopathologic correlations are very important in the study of
disease.

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Signs, symptoms and syndromes
• Symptom – subjective (abdominal pain, headache, nausea,…)
• Sign – objectively identifiable (fever, palpable mass)
• Syndrome – compilation of signs and symptoms that are characteristic
of a specific disease state

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Course of disease
- The course of a disease in the absence of any intervention is called the
natural history of the disease.

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Department of Pathology
• 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.

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Department of Pathology
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
f) The onset of permanent damage
g) Death

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Department of Pathology
The course of disease is shown with a simplified diagram as follows.
• Exposure Biological onset Clinical onset
 
Latency period Permanent damage

Death

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Department of Pathology
Outcome and consequences of disease
- Following clinical onset, disease may follow any of the following
trends:
a) Resolution can occur leaving no complication or squeale
b) The disease can settle down, but squeal/complication are left
c) It may result in death

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Department of Pathology
Death
Clinical & biologic death
- Clinical death is the reversible transmission between life and biologic
death.
- Clinical death is defined as the period of respiratory, circulatory and
brain arrest during which initiation of resuscitation(CPR) can lead to
recovery.

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Department of Pathology
 Signs indicating clinical death are
- The patient is without pulse or blood pressure and is completely
unresponsive to the most painful stimulus.
- The pupils are widely dilated
- Some reflex reactions to external stimulation 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.
- Recovery can occur with resuscitation.

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Department of Pathology
Biological Death
• 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.

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Department of Pathology
 Postmortem changes
Rigor mortis – contraction of muscle
Livor mortis – bluish discoloration on dependent part of the body
Algor mortis – cooling of the body
Autolysis – degradation of the body

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Department of Pathology
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Mechanisms of preservation:
1. to prevent autolysis and bacterial decomposition
2. to coagulate the tissue to prevent loss of easily diffusible substances
3. to protect the tissue against the deleterious effects of the various stages in
the preparation of sections and tissue processing.
4. to leave the tissues in a condition which facilitates differential staining with
dyes and other reagents.

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Department of Pathology
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Diagnostic techniques used in pathology
• The pathologist uses the following techniques to diagnose diseases:
 Histopathology
 Cytopathology
 Hematopathology
 Immunohistochemistry
 Microbiological examination
 Biochemical examination
Autopsy
Ancillary techniques

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 A. Histopathological techniques
• Histopathological 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 taken from a living person to identify the
disease.

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 - There are two types of biopsies:
(1) Incisional biopsy and
(2) Excisional biopsy.
- Incisional biopsy: only a sample of the
suspicious tissue is cut from a mass.
- Diagnostic
- Excisional biopsy: an entire abnormal
area is removed for examination under a
microscope.
- It is both therapeutic and diagnostic

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The Hematoxylin/Eosin stain is usually abbreviated as H&E stain.
It is the gold standard of staining and routinely used in histopathology
It gives the nucleus a blue color & the cytoplasm & the extracellular
matrix a pinkish color.
Read for formalin

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Normal lung PMN infiltration in broncho pneumonia/H&E/
Cytopathologic techniques
Cytopathology studies disease at cellular level from various body sites to determine the cause or nature of
disease
Cytopathologic methods:
1. Fine-needle aspiration cytology (FNAC)
2. Exfoliative cytology
3. Abrasive cytology
Applications of Cytopathology:
The main applications of cytology includes:
• Screening
• Diagnosis
• Staging and grading of malignancy
• Treatment response
• Therapeutic

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FNAC is a technique used to get cells and tissue fragments(FNAB) by aspirating the
diseased organ(tissue) using a very thin needle under negative pressure.
• The aspirated cells and fragmented tissues are then smeared, stained & studied
under the microscope to reach on diagnosis of the disease
• Superficial organs are aspirated easily: thyroid, breast, peripheral lymph nodes, skin
and soft tissues
• Image guided FNAC: lung, liver, mediastinum, pancreas, kidney, adrenal gland, GI and
retroperitoneum
• In many clinical situations, FNAC can render a definitive diagnosis either from
aspiration smears alone using well-defined cytological criteria or from smears
combined with clinical data, radiological findings, and the results of ancillary studies

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• May-Grünwald- Giemsa (MGG) stain is the routinely used stain in
FNAC as well as in other cytopathological methods, but other types of
stains can also be used including Diff-Quik, Hematoxylin and eosin
(H&E) or Papanicolaou (Pap) stain

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Comparison of cytology versus histology:

Histology Cytology
Usual planned Often spontaneous
Biopsy may not be easy Mostly used on accessible sites
Provides plenty of material for additional studies Material usually limited
Needs fixation Rapid fixation
Hours to days Result possible in minutes
Very good accuracy Accuracy good
Very good specificity Specificity okay to good
Costly Cheaper
Patient acceptability less good Patient acceptability often better
Anesthetic may be required Generally no anesthetic required
Variable risk to patient and clinician Little risk to patient or clinician

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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
• It is used to diagnose the different kinds of anemia & leukemia.

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E. Microbiological examination
• This is a method by which body fluids, excised tissue, etc. are
examined by
microscopical
cultural and
serological techniques
to identify micro-organisms responsible for many diseases.

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F. Biochemical examination

• This is a method by which the metabolic disturbances of disease are

investigated by assay of various normal and abnormal compounds in
the blood, urine, etc.

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I. Autopsy
• Autopsy is examination of the dead body to identify the cause of
death.
• This can be for
Forensic (scientific investigation of the causes of injury and death in crime) or
Clinical purposes.

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Modern Trends in Pathology
• Electron microscopy
• Immunohistochemistry
• Monoclonal antibodies
• Fluorescent labeled antibodies
• Polymerase chain reaction
• And other advanced molecular techniques
Reading assignment for detail !!!

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Ancillary (additional) techniques in
pathology
Includes many special and immunohistochemical stains

Used for detection of

Special stain
Periodic acid Schiff(PAS) Glycogen, fungi
Alcian blue Mucin
Prussian blue Hemosiderin
Ziehl Nielsen stain Acid fast bacilli

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Immunohistochemical stain commonly used:
Immunohistochemical stain Used for detecting
Estrogen and progesterone receptors Breast ca
CD markers Lymphoid cell marker
Vimentin Mesenchymal marker
Cytokeratin Epithelial cell marker

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