general and systemic pathology associate professor dr. alexey podcheko spring 2015
TRANSCRIPT
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: [email protected] Course Facilitator: Dr. Amitabha Ray, MD, Ph.DEmail: [email protected]. Meghnad Bhowmick MBBS, MScEmail: [email protected]
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
Den
sit
y o
f b
an
d
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