1.g.2014-patho~ (1.introduction-wyl)

Pathology ---

Introduction

Xi’an Jiaotong University

2017.1.2017.1.

XI’AN JIAOTONG UNIVERSITY

Page 2

Pathology is the scientific study of disease Literally: Path (pathos, suffering ) ology (logos, study)

Pathology is a bridge between basic science and clinical practice. The road taking the medicine from art to science (witch doctor, conjure man)

Pathology provides the scientific foundation for the practice of medicine Disease may be defined as an abnormal alteration of structure or function in any part of the body. Pathology is the study of structural and functional abnormalities that manifest as diseases of organs and systems.

Seeing is believing


Page 3

What is scientific methods

---A process for experimentation that is used to explore observations and answer questions. Scientists use the scientific method to search for cause and effect relationships in nature. In other words, they design an experiment so that changes to one item cause something else to vary in a predictable way.


Page 4


Page 5

Pathology is the scientific study of disease Literally: Path (pathos, suffering ) ology (logos, study)

Pathology is a bridge between basic science and clinical practice. The road taking the medicine from art to science (witch doctor, conjure man)

Pathology provides the scientific foundation for the practice of medicine Disease may be defined as an abnormal alteration of structure or function in any part of the body. Pathology is the study of structural and functional abnormalities that manifest as diseases of organs and systems.

Seeing is believing


Page 6

The Core of Pathology

Etiology or cause. Genetic (e.g., inherited mutations and disease- associated gene variants or polymorphisms) Acquired (e.g., infectious, nutritional, chemical, physical)

Pathogenesis The sequence of cellular, biochemical, and molecular events that follow the exposure of cells or tissues to an injurious agent.


Page 7

Morphologic changes The structural alterations in cells or tissues that are either

characteristic of a disease or diagnostic of an etiologic process.

Morphology remains at the heart of diagnostic pathology

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)


Page 8

The pathologist is interested not only in recognition of structural alteration, but also in their significance, i.e., the effects of these changes on cellular and tissue function and ultimately the effect of these changes on the patient. it is not a discipline isolated from the living patient, but rather a basic approach to a better understanding of disease and therefore a foundation of sound clinical medicine. (1957) stanley robbines


Page 9

To render diagnoses and guide therapy in clinical practice

Basic activities of anatomic pathology:

1). establishing the diagnosis

2). providing prognostic information,

3). most importantly for our clinicians, offering predictive

information about therapeutic modalities


Page 10

Pathologists often have been accused, and sometimes justly, of stressing the morphologic changes in disease to the neglect of functional effects. nevertheless, pathologic anatomy and histology remain as an essential foundation of knowledge about disease, without which basis, the concepts of many disease are easily distorted. 1948 W.A.D. Anderson


Page 11

History and development of pathology

Hippocrates of Kos. 460 – c. 370 BC

The first person to believe that diseases were caused naturally, not because of superstition and gods. He separated the discipline of medicine from religion, believing and arguing that disease was not a punishment inflicted by the gods but rather the product of environmental factors, diet, and living habits. However, Hippocrates did work with many convictions that were based on what is now known to be incorrect anatomy and physiology, such as Humorism


Page 12


Page 13

The history of Chinese Medicine

Huang Di Nei Jing Su Wen

五脏 : 肝、心、脾、肺、肾六腑 : 胆、胃、大肠、小肠、膀胱和三焦六淫：风，寒，暑，湿，燥，火七情：喜，怒，忧，思，悲，恐，惊

Wind, cold, heat(hot weather), damp, dryness,fire,

Happy, angry, worry, think(anxiety), sorrow(sad, grief), fear, be frightened(shock)


Page 14

An Italian anatomist ， the father of modern anatomical pathology He brought out the great work which, once for all, made pathological anatomy a science, and diverted the course of medicine into new channels of exactness or precision In his five books, treating of the morbid conditions of the body a capite ad calcem, and together containing the records of some 646 dissectionsThe Founder Of Organ Pathology

Giovanni Battista Morgagni Italian,1682-1771 DC


Page 15

A German pathologist ,the father of modern pathology His scientific writings alone crossed 2,000 in number, “Cellular Pathology ” published in 1858 is regarded as the root of modern pathology. This work also popularised the third dictum in cell theory “All cells arise only from pre-existing cells” Rudolf Ludwig Carl Virchow

(1882-1902 AD)


Page 16

Autopsy— postmortem examination (necropsy)

A highly specialized surgical

procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present. It is usually performed by a specialized medical doctor called a pathologist.

Classic Techniques Classic Techniques Of PathologyOf Pathology


Page 17

Autopsies are useful for :

1. Determining the cause of death 2. Audit of the accuracy of clinical diagnosis 3. Research into the causes and mechanisms of disease 4. Gathering accurate data and information about disease incidence and endemic 5. Education of medical students and professionals


Page 18

Biopsy --- An examination of pathologic samples from living body to set up diagnosis

The intervention of the microscope is not at all necessary to decide whether such and such a tumor, which has been removed, is or is not of cancerous nature.-- Dr. Velpeau, famous professor of clinical

surgery at the Univ.of Paris in 1853

In the 1870s, Carl Ruge of the Univ. of Berlin, introduced the surgical biopsy as an essential diagnostic tool.


Page 19

Histopathology and Cytopathology The investigation and diagnosis of disease come from the examination of tissues or isolated cell. ( tissue or cell biopsies )


Page 20

Observation and new technique of morphology

size, shapeweightcolor consistencysurfaceedge, section


Page 21

Microscopic observation (HE)

Most common and basic formalin fixed → HE (hematoxylin and eosin) stained sections


Page 22

Electron microscopy—Ultrastructural pathology

Electron microscopy has extended the range of pathology to the study of disorders at an organelle level, and to the demonstration of viruses in tissue samples from some diseases.

Early (stage 1) membranous glomerulonephritis. Two small subepithelial kappa light-chain deposits are evident (arrows). The capillary lumen is at the top.(Mag×46,200.)

coronavirus

Embryonal rhabdomyosarcoma in the deltoid muscle. Rigid myosin-ribosome complexes are randomlydistributed throughout the cytoplasm. The Z-disc substance is indicated by an arrow. (Magnification ×24,000).


Page 23

Immunohistochemistry

Tumor infiltrating lymphocytes


Page 24

S-100–positive melanoma. Note the nuclear reactivity, characteristic of melanoma

Keratin positivity in breast cancer , which is typically seen in carcinomas


Page 25

Candida. This example from the esophagus shows magenta pseudohyphae and yeasts (arrows, periodic-acid Schiff stain).

Cryptococcus. The organismsare significantly larger and show a range of sizes and shapes on Gomori’s methenamine silver stain.

Microbiology---tissue section based


Page 26

Mycobacteria on acid-fast bacteria stain. In this example, tiny wine-red rods are visiblewithin the tissue (arrows).

Helicobacter pylori. The bacilli are sometimes visible on hematoxylin and eosin stain, as seen here (arrows), in the pits of the gastric mucosa Barry J.Marshall the University of Western Australia 2005 nobel prize


Page 27

Molecular Biology…….

In situ hybridization

HPV DNA &RNA in situ hybridization in squamous cell carcinoma


Page 28

Polymerase chain reaction amplification of DNA extracted from microdissected paraffin-embedded tissue with human papillomavirus (HPV)-16 E7-type primers, processed by Southern blotting, and hybridized to HPV-16 E7 DNA. Lanes 1–5 show the following: (1) no primers, no DNA; (2) primers only; (3) DNA only; (4) microdissected stromal tissue; (5) microdissected tumor tissue


Page 29

Cytogenetics and Fluorescence in Situ Hybridization FISH

(Left) Achromosome spread from a human body cell midway through mitosis, when the chromosomes are fully condensed. This preparation was treated with fluorescent-labeled staining reagents that allow each of the 22 pairs and the X and Y (Right) Chromosomes from the preparation on the left arranged in pairs in descending order of size, an array called a karyotype. The presence of X and Y chromosomes identifies the sex of the individual as male Chromosome Painting---multiplex fluorescence in situ hybridization (M-FISH)

Her2 amplification in breast cancer (FISH and IHC)


Page 30

Types of primers that can be used to initiate reverse transcription and synthesis of complementary DNA (cDNA) for reverse transcriptase polymerase chain reaction (RT-PCR).

Verification of the specificity of the polymerase chain reaction (PCR) product


Page 31

Microsatellites are DNAsequences that are repeated a variable number of times in thegenome and inherited in a mendelian fashion. The microsatellite region is amplified by polymerasechain reaction (PCR); the products are separated by gel electrophoresis,processed by Southernblotting, and hybridized to a sequence-specific probe.

Microsatellite instability in colon cancer


Page 32

Animal experimentation

Transplant tumor model in nude mice


Page 33

Tissue and cell culture


Page 34

Flow cytometry Image analysis Image digitizing technology ………. The study of the nature of disease , which constitutes pathology in the broad sense, has many facets. Any science or technique which contributes to our knowledge of the nature and constitution of disease belongs in the realm of pathology.


Page 35

The Branch of Pathology

Modern Pathology (1920S-)Ultrastructural PathologyMolecular PathologyImmunopathologyGenetic Pathology Remember: start from cellular pathology and return to cellular pathology ultimately The cell is the basic

unit of structure and organization in organisms


Page 36

Pathology is best taught and learnt in two stages:

General pathology: A discussion of disease fundamentals oriented horizontally (nature of process). i.e. injury, repair, inflammation, neoplasia.

Systemic pathology: A more detailed discussion of diseases oriented vertically. i.e. cardiovascular diseases, respiratory diseases, alimentary diseases, endocrine diseases, renal diseases, infectious diseases.


Page 37

LEARNING OF PATHOLOGY

There are two apparent difficulties that face the new student of pathology: language and process. (1) Language——Vocabulary of special terms: These need to be learnt and understood not just because they are the language of pathology; they are also a major part of the language of clinical medicine.Concepts to master: lots of concept is basic processes of studying pathology. Cause(why) + Location (where) +Change(what)


Page 38


(2) The process —— a logical and orderly way of thinking about disease. Incidence Aetiology Pathogenesis Pathological and clinical feature Complications and sequel Prognosis Treatment


Page 39


(3) Pathology is learnt through a variety of media. Textbook Lecture Practical classes (the gross and microscopic observation) Postmortem teaching (autopsy)


Page 40


(4) The problem-oriented and disease-oriented approach. In learning pathology, the disease-oriented approach is more relevant because medical practitioners require knowledge of disease (e.g. pneumonia, cancer, ischemic heart disease) so that correct diagnoses can be made and the most appropriate treatment given.