GENERAL AND SYSTEMIC PATHOLOGY 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

• 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

ATTENDANCE POLICY

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

AdministrationCourse Director – Dr. Alexey Podcheko MD, Ph.D, Email: apodcheko@mail.sjsm.org Course Facilitator: Dr. Amitabha Ray, MD, Ph.DEmail: aray@mail.sjsm.orgDr. Meghnad Bhowmick MBBS, MScEmail: mbhowmick@mail.sjsm.org

My background:1. 1989-1995 – MD (General Practitioner) from Smolensk State School of Medicine,

Russia2. 1995-1998 – Residency at Departments of Pathology and Clinical Endocrinology

of Smolensk State Medical School 3. 1998-2000- Assistant Professor at Department of Clinical Endocrinology4. 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 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

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 beta-cell 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 disease3. The study of the gross and microscopic patterns of disease

History

Rudolph Virchow

1821-1902

The Father of Modern PathologyAll diseases are the results of visible

cell abnormalities

All diseases are the results of visible cell abnormalities

Who is Pathologist?

Pathologist:

• Diagnostician

• Teacher

• Scientific Researcher

Physician who specializes in the diagnosis and management of human disease by laboratory methods

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

Patient: 46 year-old man Heavy smoker Complains of:

WeaknessChronic coughChest pain

•Physical and Lab Findings:

Elevated Blood PressureElevated Serum Calcium

A Case Study in Lung Cancer

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 aConsultant

•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 CONTENTMajor 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

• 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

What kind of questions will be asked on USMLE?

Cell Pathology

-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)

SOME EXAMPLES:

Today’s Topica) Definitionsb ) Techniques in the Pathology

Methods Used in Pathology

1. Gross examination of organs:a. What organ are you looking atb. What is wrong

How to determine if there is something wrong with the organ:

a. Sizeb. Shapec. Consistencyd. Colore. But the most important – read history!!!!

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)

Autopsy: Main Techniques

Normal LungPulmonary 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.

Which X-ray is normal?

NormalEmphysema

Methods Used in Pathology

2. Light Microscopy using various staining techniques:

a.Hematoxylin and EosinHematoxylin 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.

Which image represent normal lung?

Emphisema !!! Normal lung tissue

Structures stained by Hematoxylin/Eosin

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

• 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

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 red (normal light microscopy)

Amyloid in vessel wall is apple green (Green+yellow) when 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 stainPeriodic 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 mature megakaryocytes. Gauchers' disease marrow( lack of glucocerebrosidase)

Gram stain

Boxcar-shaped gram-positive Clostridium perfringens in gangrenous tissue

Gram-negative Pseudomonas aeruginosa bacteria (pink-red rods).

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)

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

ImmunoHystoChemistry (IHC)

ImmunofluorescentImmunoperoxydase

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 Origin of Positively stained cells

Cytokeratin Epithelial Cells

Vimentin Mesenchymal cells

Desmin Muscle cells

Prostate Specific Antigen (PSA)

Prostate epithelium

Transmission Electron Microscopy

• Renal diseases

• Neoplasms

• Infections

• Genetic Disorders

Crescentic glomerulonephritis.

Transmission Electron Microscopy• Renal diseases

• Neoplasms

• Infections

• Genetic Disorders

pulmonary adenocarcinoma

mesothelioma

Transmission Electron Microscopy• Renal diseases

• Neoplasms

• Infections

• Genetic Disorders

A AdenovirusB Epstein-Barr virusC RotavirusD Paramyxovirus

Transmission Electron Microscopy

• Renal diseases

• Neoplasms

• Infections

• Genetic Disorders

Ganglion cells in Tay-Sachs disease

Molecular Biology Techniques• Protein Electrophoresis/Western Blotting

• Protein Electrophoresis/Western Blotting

Staining of gel with special

dye

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f b

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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