Transcript Introduction to Pathology Course

GENERAL AND SYSTEMIC PATHOLOGY
Associate Professor
Dr. Alexey Podcheko
Spring 2015
How to download slides of
Pathology course lectures?
http://www.sjsm.org/moodle/
TEXTBOOKS You will need for the
course:
• BASIC PATHOLOGY – ROBBINS 9th
Edition
• Rubin's Pathology: Clinicopathologic
Foundations of Medicine 6th Edition
• Illustrated Q&A Review Of Rubin's
Pathology, 2nd Ed (!)
• Robbins and Cotran Review of Pathology,
3rd Edition (!)
PATHOLOGY
• GENERAL PATHOLOGY DEALS WITH BASIC
CONCEPT OF VARIOUS DISEASE PROCESSES
IN THE BODY, LIKE THE CAUSES AND
MECHANISMS
OF
DISEASE
AND
THE
ASSOCIATED
ALTERATIONS
IN
THE
STRUCTURE AND THE FUNCTION
• SYSTEMIC PATHOLOGY DEALS WITH THE
DISEASE
PROCESS
AFFECTING
VARIOUS
SYSTEMS AND SPECIFIC ORGANS IN THE BODY
ATTENDANCE POLICY
• Students must attend at least 80% of
lectures. Attendance will be monitored
through Moodle
• Student must read/review appropriate
textbook chapter and download the lecture
slides before the lecture (Link is above)
• Any student falling short of 80% attendance
please refer to the Attendance policy of
SJSM Anguilla campus
Organization of Course
~12 weeks
~ 60 Lectures/Seminars (5 times/week)
EVALUATIONS:
MCQs Quizzes:
During lectures for attendance (usually
2 questions)
50 question quiz will be administered
during lab session one time per block
Laboratory Classes
• Learning will be based on clinical cases –
Problem Based Learning, discussion and
review of clinical vignettes, (MCQs from various
test banks)
• Review of pathology slides: real and virtual
GRADING
• Grading for course will be provided
based on the following schedule:
Final course score and grade will be calculated based on the
following formula:
Final course score=(A+B+C+D)/4
Curving
• Note: Curving will be performed only if
average score for MCQ exam in the group
is below 70. Curving will be done only for
MCQ exams.
• Aim of curving is to reach average score 70
in the tested population.
• No curving for quizzes, labs and poster
presentations!
Final Tips on how to successfully
pass the Pathology Course:
• 1. Read the Robbin’s or Rubin’s chapter and
download slides before the lecture
• 2. During lectures make notes!
• 3. Do your best on the quizzes
• 4. Do not miss labs
• 5. Review your notes and all MCQs from
Robbins and Rubin’s Review textbook chapters
before exam!
• 6. Do not leave reading of textbooks on the day
before exam
• 7. Final tip: answers for all exam questions can
be founded in the lecture slides
Administration
Course Director – Dr. Alexey Podcheko MD, Ph.D,
Email: [email protected]
Course Facilitator: Dr. Amitabha Ray, MD, Ph.D
Email: [email protected]
Dr. Meghnad Bhowmick MBBS, MSc
Email: [email protected]
My background:
1. 1989-1995 – MD (General Practitioner) from Smolensk State School of Medicine,
Russia
2. 1995-1998 – Residency at Departments of Pathology and Clinical Endocrinology
of Smolensk State Medical School
3. 1998-2000- Assistant Professor at Department of Clinical Endocrinology
4. 2000-2005 - Ph.D. in Molecular Biology at Nagasaki University, School of
Medicine, (Japan)
5. 2005-2010 – Postdoctoral Research Associate at Department of Laboratory
Medicine and Pathobiology, University of Toronto, School of Medicine
6. 2010- Associate Professor at Department of Basic Sciences SJSM
Research Projects:
Ionizing Radiation and Thyroid
Cancer
-To clarify the mechanisms of radiationinduced thyroid carcinogenesis
-To develop novel diagnostic techniques
and gene/molecular-targeted therapy for
thyroid cancer
-To analyze genomic instability in multistep process of radiation carcinogenesis
-To analyze radiation-induced cellular and
molecular response
-To identify the molecular mechanisms of
cellular senescence and stress response
-To clarify the mechanisms of UV or
ionizing radiation-induced DNA damage
repair
May the tree thrive.
Frederick Banting joined by Charles Best in office, 1924
My research in Diabetes area
•Role of immunomodulators
(thymic extracts) on protection
against experimental Type I
Diabetes
•Identification of novel genes
involved in beta-cell growth and
survival
•Cloning and characterization of
novel positive regulator of betacell growth - Plekstrin Homology
Interacting Protein 1 (PHIP1)
My research/publications:
OBJECTIVES of the Course
WHAT IS PATHOLOGY?
Pathos - Pathos is a Greek term for deep emotion, passion, or suffering.
Logos - The Greek word logos traditionally meaning word, thought,
principle, speech or study
Three Definitions of Pathology:
1. Pathology is the study of diseases.
2. Pathology is the study of essential nature of disease, disease
process, and functional changes in organs and tissues that
cause or are caused by disease
3. The study of the gross and microscopic patterns of disease
History
All diseases are the results of
visible cell abnormalities
Rudolph Virchow
1821-1902
The Father of
Modern Pathology
All diseases are the results of
visible cell abnormalities
Who is Pathologist?
Physician who specializes in the diagnosis and
management of human disease by laboratory
methods
Pathologist:
• Diagnostician
• Teacher
• Scientific
Researcher
Pathology
Anatomic Pathology
Specialty:
Microscopic analysis of
tissue changes.
Pathologist plays a central
role in the diagnosis of
surgically removed tissues
Clinical Pathology
Specialty:
•Hematology
•Microbiology
•Immunology
•Clinical Chemistry
•Blood Bank (Transfusion
Medicine)
•Laboratory Data
Management
•Molecular Pathology
Anatomic Pathology:
Surgical Pathology
Analysis of Biopsies and
Surgical Specimens
Surgically Removed Tissue
Frozen Section/
Gross and Microscopic
Evaluation
Diagnosis and Prognostic
Information
A Case Study in Lung Cancer
Patient:
 46 year-old man
 Heavy smoker
Complains of:
Weakness
Chronic cough
Chest pain
•Physical and Lab Findings:
Elevated Blood Pressure
Elevated Serum Calcium
A Case Study in Lung Cancer
CT imaging reveals mass
in right lung
Patient taken to surgery
Mass biopsied and sent for
frozen section
Microscopic evaluation yields:
- Precise diagnosis
- Extent of disease
- Information needed to
determine course of action
Anatomic Pathology:
Cytopathology
A Case Study in Thyroid Cancer
Patient with thyroid mass receives a tracer
dose of radioactive iodine, which reveals a
“cold” nodule
Pathologist performs fine- needle
aspiration (FNA)
Surgeon and oncologist determine
course of action based on
pathologist’s FNA diagnosis
Mass removed during surgery
Anatomic Pathology:
Autopsy
Autopsy provides insight into
disease processes and the
influence of therapy on disease:
 Reveals cause of death
 May detect previously undiagnosed
genetic disorders – information that
may benefit living family members
 Provides feedback to physicians
involved in patient care:
1. Accuracy of diagnoses
2. Effectiveness of treatment
Clinical Pathology
Clinical pathology specialty
laboratories include:
 Hematology
 Microbiology
 Immunology
 Clinical Chemistry
 Toxicology
 Transfusion Medicine
Pathologists serve as consultants
to other physicians by:
 recommending appropriate tests
 interpreting test results
Cytology
Dermatopathology
Molecular Pathology
•DNA sequencing to identify
infectious agents
•Molecular identification of
chromosomal rearrangements
•Genetic alterations
•Prenatal screening for hemoglobin
disorders and metabolic diseases
•Genetic susceptibility to cancer
Forensic
Hematopathology
The Pathologist as a
Consultant
•Interprets laboratory results
•Advises physicians on
appropriate diagnostic tests
•Contributes to medical and
surgical patient management
decisions
•Serves on hospital committees
(e.g. quality assurance, blood
utilization, infection control)
•Updates physicians about
laboratory medicine in
Continuing Medical Education
programs
The Pathologist in
Research
Investigates the causes and mechanisms
of diseases by:
•Tracing new diseases to their origins
•Improving diagnostic approaches to
diseases
•Identifying the genetic basis for patient
response to treatments
•Identifying new pathogenic bacteria and
other infectious agents
•Identifying genes involved in specific
cancers
What Kinds of People Go Into
Pathology?
Lectures: ACADEMIC CONTENT
Major Themes
disease - major categories
emphasis on the following:
• etiology
• pathogenesis (as a variation of normal
physiology)
• structural alterations
• clinical manifestations in patient and
correlation with diagnosis and treatment
What kind of questions will
be asked on USMLE?
• ETIOLOGY - cause
• PATHOGENESIS – sequence of
changes which leads to disease
• MORPHOLOGY - gross and
microscopic changes
• CLINICAL EXPRESSION – disease
presentation, clinical symptoms
and prognosis, progression of
disease
SOME EXAMPLES:
Cell Pathology
-5 LECTURES ON CELL INJURY AND CELL
DEATH INCLUDING FOLLOWING TOPICS:
•
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•
•
•
•
•
•
CELL INJURY
NECROSIS
APOPTOSIS
SENESCENCE
INTRACELLULAR ACCUMULATIONS
CELL GROWTH AND DIFFERNTIATION
REVIEW OF MATERIAL FOR EXAM
EXAM (USMLE TYPE)
Today’s Topic
a) Definitions
b ) Techniques in the Pathology
Methods Used in Pathology
1. Gross examination of organs:
a. What organ are you looking at
b. What is wrong
How to determine if there is something
wrong with the organ:
a.
b.
c.
d.
e.
Size
Shape
Consistency
Color
But the most important – read history!!!!
Autopsy: Main Techniques
1. En Masse (Le Tulle)
Organs are removed as a single bulky aggregate
2. En Bloc (Ghon/Zenker)
3. Virchow’s
4. Rokitansky (in situ)
Pulmonary emphysema
Normal Lung
-Note the dilation of airspaces.
-This pattern is most characteristic for the centrilobular pattern of emphysema, Most often
associated with a history of smoking.
-The damage to the lung from smoking is in part the result of accentuation of neutrophil
proteases, which over time destroy alveolar walls.
Which X-ray is normal?
Emphysema
Normal
Methods Used in Pathology
2. Light Microscopy using various staining
techniques:
a.Hematoxylin and Eosin
Hematoxylin
Eosin
Stains blue to
purple
Stains pink to red
Nuclei
Cytoplasm
Nicleoli
Collagen
Bacteria
Fibrin
Calcium
RBC
Thyroid colloid
Other cell proteins
Structures stained by Hematoxylin/Eosin
Normal thyroid gland is
composed of follicles lined by
cuboidal epithelium and filled
with pink colloid
Medullary carcinoma of
thyroid. These neoplasms are
derived from the thyroid "C"
cells and, therefore, have
endocrine features such as
secretion of calcitonin.
Structures stained by Hematoxylin/Eosin
Which image represent normal lung?
Emphisema !!!
Normal lung tissue
What are other high yield stains for
USMLE?
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•
Prussian blue stain
Congo Red stain
Acid Fast (Ziel-Neelson, Fite)
Periodic Acid-Schiff (PAS)
Gram stain
Trichrome
Reticulin
Prussian blue reaction –staining
for Iron
• Prussian blue stain involves the treatment of
sections with acid solutions of ferrocyanides.
Any ferric ion (+3) present in the tissue
combines with the ferrocyanide and results in
the formation of a bright blue pigment called
Prussian blue, or ferric ferrocyanide.
• This is one of the most sensitive histochemical
tests and will demonstrate even single granules
of iron in blood cells.
• Small amounts of ferric iron are found normally
in the spleen and bone marrow. Excessive
amounts are present in hemochromatosis and
hemosiderosis.
Prussian blue reaction –staining
for Iron
Acute intra-alveolar hemorrhage
and hemosiderin-laden
macrophages, reflecting previous
hemorrhage
Hemochromatosis in cardiac
muscle
Congo Red stain
Amyloid in vessel wall is stained Amyloid in vessel wall is apple
green (Green+yellow) when
red (normal light microscopy)
viewed with fully polarized light
amyloid birefringence !!!
Acid Fast stain
Mycobacterium avium infection
in a patient with AIDS, showing
massive infection with acid-fast
organisms.
PAS stain
Periodic acid-Schiff (PAS) is a staining method used to detect
glycogen in tissues. The reaction of periodic acid selectively
oxidizes the glucose residues, creates aldehydes that react with the
Schiff reagent and creates a purple-magenta color.
Lupus nephritis
“wire loop” lesions
PAS
positive
megakaryocytes.
disease
marrow(
glucocerebrosidase)
mature
Gauchers'
lack
of
Gram stain
Boxcar-shaped
gram-positive
Clostridium
perfringens
in
gangrenous tissue
Gram-negative
Pseudomonas
aeruginosa bacteria (pink-red
rods).
Trichrome (Mason) stain
Detection of collagen, (to differentiate between collagen and
smooth muscle in tumors, outline collagen deposits in
diseases such as cirrhosis or various types of fibrosis)
Non-Alcoholic Steatohepatitis
(NASH), showing perivenular
fibrosis and perisinusoidal
fibrosis (blue fibers)
Variable myocyte hypertrophy
and
interstitial
fibrosis
(collagen is highlighted as blue)
•
Reticulin
stain
The reticulin stain is useful in parenchymal organs such as
•
A reticulin stain occasionally helps to highlight the growth
liver and spleen to outline the architecture
pattern of neoplasms.
Normal Liver
ImmunoHystoChemistry (IHC)
Immunoperoxydase
Immunofluorescent
Anti-cytokeratin Abs
Most frequently used for
diagnostic of cancers
Most frequently used for
diagnostic of renal and skin
diseases (autoimmune origin)
Most frequently mentioned in
USMLE immunohistostainings
Antibodies
Cytokeratin
Origin of Positively
stained cells
Epithelial Cells
Vimentin
Mesenchymal cells
Desmin
Muscle cells
Prostate Specific
Antigen (PSA)
Prostate epithelium
Transmission Electron Microscopy
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Renal diseases
Neoplasms
Infections
Genetic Disorders
Crescentic glomerulonephritis.
Transmission Electron Microscopy
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Renal diseases
Neoplasms
Infections
Genetic Disorders
pulmonary
adenocarcinoma
mesothelioma
Transmission Electron Microscopy
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Renal diseases
Neoplasms
Infections
Genetic Disorders
A
B
C
D
Adenovirus
Epstein-Barr virus
Rotavirus
Paramyxovirus
Transmission Electron Microscopy
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Renal diseases
Neoplasms
Infections
Genetic Disorders
Ganglion cells in Tay-Sachs disease
Molecular Biology Techniques
• Protein Electrophoresis/Western Blotting
• Protein Electrophoresis/Western Blotting
Density of band
Staining of
gel with
special dye
Molecular Biology Techniques
• PCR (diagnosis of various infections, mutations)
• Microarray (analysis of expression of all known genes
expressed in particular tissue, e.g tracing origin of
secondary tumor, risk assessment of premalignant
lesions, prediction of drug resistance)
• Whole genome sequencing