OBJECTIVES

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GENERAL AND SYSTEMIC PATHOLOGY
Associate Professor Dr. Alexey Podcheko Spring
2015
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How to download slides of Pathology course
lectures?

• http//www.sjsm.org/moodle/

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TEXTBOOKS You will need for the course

• BASIC PATHOLOGY ROBBINS 9th Edition
• Rubin's Pathology Clinicopathologic Foundations
  of Medicine 6th Edition
• Illustrated QA Review Of Rubin's Pathology, 2nd
  Ed (!)
• Robbins and Cotran Review of Pathology, 3rd
  Edition (!)

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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

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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

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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

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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

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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(ABCD)/4
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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!

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Final Tips on how to successfully pass the
Pathology Course

• 1. Read the Robbins or Rubins 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 Rubins 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

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Administration
Course Director Dr. Alexey Podcheko MD, Ph.D,
Email apodcheko_at_mail.sjsm.org Course
Facilitator Dr. Amitabha Ray, MD, Ph.D Email
aray_at_mail.sjsm.org Dr. Meghnad Bhowmick MBBS,
MSc Email mbhowmick_at_mail.sjsm.org

• My background
• 1989-1995 MD (General Practitioner) from
  Smolensk State School of Medicine, Russia
• 1995-1998 Residency at Departments of Pathology
  and Clinical Endocrinology of Smolensk State
  Medical School
• 1998-2000- Assistant Professor at Department of
  Clinical Endocrinology
• 2000-2005 - Ph.D. in Molecular Biology at
  Nagasaki University, School of Medicine, (Japan)
  
• 2005-2010 Postdoctoral Research Associate at
  Department of Laboratory Medicine and
  Pathobiology, University of Toronto, School of
  Medicine
• 2010- Associate Professor at Department of Basic
  Sciences SJSM

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Research Projects Ionizing Radiation and Thyroid
Cancer -To clarify the mechanisms of
radiation-induced thyroid carcinogenesis -To
develop novel diagnostic techniques and
gene/molecular-targeted therapy for thyroid
cancer -To analyze genomic instability in
multi-step 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
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Frederick Banting joined by Charles Best in
office, 1924
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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 beta-cell growth - Plekstrin
  Homology Interacting Protein 1 (PHIP1)

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My research/publications
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OBJECTIVES of the Course
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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
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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
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Who is Pathologist?
Physician who specializes in the diagnosis and
management of human disease by laboratory methods

• Pathologist
• Diagnostician
• Teacher
• Scientific Researcher

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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

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Anatomic Pathology Surgical Pathology

• Analysis of Biopsies and Surgical Specimens
• Surgically Removed Tissue
• Frozen Section/
• Gross and Microscopic Evaluation
• Diagnosis and Prognostic Information

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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

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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

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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 pathologists
FNA diagnosis Mass removed during surgery
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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

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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

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Cytology
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Dermatopathology
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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

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Forensic
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Hematopathology
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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

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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

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What Kinds of People Go Into Pathology?
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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

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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

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Cell Pathology
SOME EXAMPLES

• -5 LECTURES ON CELL INJURY AND CELL DEATH
  INCLUDING FOLLOWING TOPICS
• CELL INJURY
• NECROSIS
• APOPTOSIS
• SENESCENCE
• INTRACELLULAR ACCUMULATIONS
• CELL GROWTH AND DIFFERNTIATION
• REVIEW OF MATERIAL FOR EXAM
• EXAM (USMLE TYPE)

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• Todays Topic
• Definitions
• b ) Techniques in the Pathology

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Methods Used in Pathology

• 1. Gross examination of organs
• What organ are you looking at
• What is wrong

• How to determine if there is something wrong with
  the organ
• Size
• Shape
• Consistency
• Color
• But the most important read history!!!!

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Autopsy Main Techniques
1. En Masse (Le Tulle) Organs are removed as a
single bulky aggregate 2. En Bloc
(Ghon/Zenker) 3. Virchows 4. Rokitansky (in
situ)
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Normal Lung
Pulmonary emphysema
-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.
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Which X-ray is normal?
Emphysema
Normal
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Methods Used in Pathology

• 2. Light Microscopy using various staining
  techniques
• 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
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Structures stained by Hematoxylin/Eosin
Medullary carcinoma of thyroid. These neoplasms
are derived from the thyroid "C" cells and,
therefore, have endocrine features such as
secretion of calcitonin.
Normal thyroid gland is composed of follicles
lined by cuboidal epithelium and filled with pink
colloid
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Structures stained by Hematoxylin/Eosin
Which image represent normal lung?
Emphisema !!!
Normal lung tissue
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What are other high yield stains for USMLE?

• Prussian blue stain
• Congo Red stain
• Acid Fast (Ziel-Neelson, Fite)
• Periodic Acid-Schiff (PAS)
• Gram stain
• Trichrome
• Reticulin

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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.

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Prussian blue reaction staining for Iron
Hemochromatosis in cardiac muscle
Acute intra-alveolar hemorrhage and
hemosiderin-laden macrophages, reflecting
previous hemorrhage
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Congo Red stain
Amyloid in vessel wall is apple green
(Greenyellow) when viewed with fully polarized
light amyloid birefringence !!!
Amyloid in vessel wall is stained red (normal
light microscopy)
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Acid Fast stain
Mycobacterium avium infection in a patient with
AIDS, showing massive infection with acid-fast
organisms.
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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.

PAS positive mature megakaryocytes. Gauchers'
disease marrow( lack of glucocerebrosidase)
Lupus nephritis wire loop lesions
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Gram stain
Boxcar-shaped gram-positive Clostridium
perfringens in gangrenous tissue
Gram-negative Pseudomonas aeruginosa bacteria
(pink-red rods).
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Trichrome (Mason) stainDetection of collagen,
(to differentiate between collagen and smooth
muscle in tumors, outline collagen deposits in
diseases such as cirrhosis or various types of
fibrosis)
Variable myocyte hypertrophy and interstitial
fibrosis (collagen is highlighted as blue)
Non-Alcoholic Steatohepatitis (NASH), showing
perivenular fibrosis and perisinusoidal fibrosis
(blue fibers)
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Reticulin stain

• The reticulin stain is useful in parenchymal
  organs such as liver and spleen to outline the
  architecture
• A reticulin stain occasionally helps to highlight
  the growth pattern of neoplasms.

Normal Liver
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ImmunoHystoChemistry (IHC)
Immunofluorescent
Immunoperoxydase
Anti-cytokeratin Abs
Most frequently used for diagnostic of cancers
Most frequently used for diagnostic of renal and
skin diseases (autoimmune origin)
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Most frequently mentioned in USMLE
immunohistostainings
Antibodies Origin of Positively stained cells
Cytokeratin Epithelial Cells
Vimentin Mesenchymal cells
Desmin Muscle cells
Prostate Specific Antigen (PSA) Prostate epithelium
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Transmission Electron Microscopy

• Renal diseases
• Neoplasms
• Infections
• Genetic Disorders

Crescentic glomerulonephritis.
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Transmission Electron Microscopy

• Renal diseases
• Neoplasms
• Infections
• Genetic Disorders

pulmonary adenocarcinoma
mesothelioma
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Transmission Electron Microscopy

• Renal diseases
• Neoplasms
• Infections
• Genetic Disorders

A Adenovirus B Epstein-Barr virus C Rotavirus D
Paramyxovirus
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Transmission Electron Microscopy

• Renal diseases
• Neoplasms
• Infections
• Genetic Disorders

Ganglion cells in Tay-Sachs disease
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Molecular Biology Techniques

• Protein Electrophoresis/Western Blotting

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• Protein Electrophoresis/Western Blotting

Staining of gel with special dye
Density of band
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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

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