1 Introduction and Cell Adaptation

Introduction to Pathology
Wenyan Zhang
Department of Pathology
West China School of Medicine
March.2018
Prof. QC Chen & Prof. Sadie C. F. Kiang
Prof. Pao-Chaug Hou

Related content
• Course Objective ：
Pathology is a scientific study of disease.
It is a discipline that bridges clinical practice
and basic science.
It involves the investigation of the
morphologic and functional changes in cells,
tissues, and organs that underlie diseases.
Related content
• Knowledge frame
General pathology - the fundamental
cellular and tissue responses to abnormal
stimuli that underlie all diseases
Systemic pathology- the particular
responses of specialized tissues and organs
to more or less well-defined stimuli
• Reference books ：
1. Robbins Basic Pathology: with Student Consult
Online Access. 9th edition, Kumar V, Abbas
AK, Aster JC, et al, eds, 2012, Elsevier
Sauders
Rubin’s Pathology: Clinicopathologic
Foundations of Medicine.
7th edition, Rubin E, Corstein F, Rubin R,
et al, eds, 2014,
Lippicott Williams & Wilkins
Teaching materials download URL
• http://cc.scu.edu.cn/G2S/Showsystem/Index.aspx
• Teaching staff
Lecture (64 credit hours)
Associate Credit Lecturers Credit
professors hours hours
7 36 8 28
Practice (48 credit hours)

Lecturers Credit Resident Credit
hours /Postgraduate hours
1 96 2 48
Criteria of assessment
Total scores: 100%
Final examination 50%
Visual recognition skills 20%
Quiz (practice) 20%
Attendance and home works 10%
Correspondence
• Director:
Lily Jiang 85423847 879876047@qq.com
• Teaching secretary :
Weiya Wang 85423847 151422303 @qq.com
• Where there is
love of medicine,
there is love of
humankind.
--
Hippocrates
(460-377 BC)
The most common diseases in
developing countries
• Infectious diseases (viral hepatitis,
tuberculosis, bacterial pneumonia,
bacterial diarrheas, AIDS, SARS, bird
flu and Streptococci swine II et al)
• Atherosclerosis and hypertension
• Cancer
• Emphysema and chronic bronchitis
• Disease could reasonably be defined as
internal problems that cause pain and/or
interfere with a person's ability to work,
play, and/or love others.
• Pathology is the scientific study of
disease academically.
logos = study
pathology
pathos = suffering
Pathology
• A bridge between clinical medicine and basic
medical sciences for medical students
• Involves the investigation of the underlying
causes (etiology) of disease & the
mechanisms (pathogenesis)
• One of the most important methods to
diagnose disease in clinical practice
Four Cores of Pathology
• Etiology (causes of diseases)
– Genetic
– Acquired
• Pathogenesis (mechanisms)
• Pathological changes (lesions)
– Morphological changes (anatomical pathology)
– Functional changes (pathophysiology)
• Clinical manifestations (signs and symptoms)
• Sequelae (healing, complications, death)
• “As is our pathology, so is
our medicine”
• “Ask not what disease the

patient has, but rather
what patient the disease
has.”
Sir William Osler (1849-1919)

Canadian physician and medical historian
Member of Big Four who established Johns Hopkin’s medical
school
What pathologists do?
• SURGICAL PATHOLOGY
– Interpret biopsies (e.g., skin, breast,
gastrointestinal)
– Evaluate surgical resection specimens (e.g.,
colectomy, nephrectomy, mastectomy)
– Frozen sections (intra-operational rapid
diagnosis)
What pathologists do?
• CYTOPATHOLOGY (e.g.Pap smears, FNA - Fine
Needle Aspiration)
• CLINICAL PATHOLOGY
– Hematology (Peripheral blood smear, bone marrow,
coagulation disorders)
– Chemistry (Blood, urine, cerebrospinal fluid,
effusions)
– Microbiology
– Blood bank
• AUTOPSY PATHOLOGY
Fine Needle Aspiration Histology, HE stain
Breast cancer: mastectomy plus lymph node dissection
Sentinel lymph node biopsy
Sentinel lymph node biopsy
Cryptococcus neoformans
Cryptococcus neoformans — GMS stain
Mucor
Aspergillus
Hodgkin Lymphoma, Reed-Sternberg cell
CD30+ Reed-
Sternberg cells
Hodgkin lymphoma
袖套现象
瘤巨细胞散在分布
Immunochemistry staining
CD10 Mum-1 BCL-6
GCET-1 FOXP-1 LMO-2
Hans 分型： GCB 型； Choi 分型： ABC 型； Tally 分型： GCB 型

Fluorescence in situ hybridization, FISH
Representative images of dual-colour break apart probe
signal patterns in normal (A) and abnormal (B) cells, and dual-colour
dual-fusion signal patterns in normal (C) and abnormal (D) cells.
21q22.2 BAC clone detects Down syndrome
antenatal examination
amniotic fluid http://www.uphs.upenn.edu/penngen/gtp/cmc_images.html
Anaplastic large cell lymphoma (ALCL)
LSI ALK Dual Color, Break Apart Rearrangement Probe
2p23
L1100180, F/46, L1100259, M/15,

Inguinal LN, ALCL Cervical LN, ALCL
Rhunbrant, 17th century
Autopsy
Goal of pathology for medical
students
• Does become a physician or a pathologist?
Physician or surgeon mostly
• Be understand and analyze the relationship
between pathologic changes and clinical
manifestations
• Be able to develop a correct diagnosis
• Be able to communicate with professionals
and patients
How to study pathology?
• Medical terms and nomenclatures
• Hypertrophy Hyperplasia
• Atrophy Metaplasia
• The relationship between clinical

manifestations and pathologic changes
• The core for studying pathology:
Functional changes
Characteristic (Pathophysiology)
morphologic lesions (lesions)
Pathogenesis
Clinical manifestations Etiology
Background
• Basic medical sciences (anatomy,
histology, physiology, biochemistry,
immunology, microbiology, parasitology, et
al)
• Medical terms (e.g. hyperplasia, et al)
• Clinical knowledge (physical examination,
laboratory tests, X-ray, CT, et al)
• Reference books
Approaches:
• Laboratory practice:
• gross specimen
glass slides
• Clinicopathologic conference
(CPC)
• Autopsy demonstration
(real or video)
Heart infarct:
L: gross appearance shows
an infarct in left anterior wall of
Heart
Ventricle
infarct
R: microscopic picture of
myocardial infarct.
Note the Myocardial fibers lost the dark blue stain of nuclei
CPC
Recommend internet web sites:
• http://www-medlib.med.utah.edu/webPa
th/webpath.html
• http://www.hxyx.com or
http://219.221.200.61
• http://www.scu.edu.cn/ or
http://202.115.96.43
Summary of introduction
• The definitions
– disease pathology
– lesion pathologist
• The rule of pathology in medical
education and clinical practice
• How to study pathology
Cell Injury, Adaptation &
Death
Cell Injury, Adaptation and
Death
• Overview of cell injury
• Causes of cell injury
• Cellular adaptation to injury
• Mechanisms of cell injury
• Reversible and irreversible cell injury
• Programmed cell death---- apoptosis
• Cellular aging
• Obesity
Cell Injury, Adaptation and
Death
• Overview of cell injury
• Causes of cell injury
• Cellular adaptation to injury
• Mechanisms of cell injury
• Reversible and irreversible cell injury
• Programmed cell death---- apoptosis
• Cellular aging
• Obesity
Overview of cell injury
• Homeostasis requires functional
cooperation in widely distributed cells.
Normal cells
homeostasis
Reversible Lethal
Reversible
Adaptative cells Cell death
atrophy, necrosis
hypertrophy Reversible Lethal apoptosis
hyperplasia Reversible
metapllasia injured cells
intracellular accumulations,
degeneration
A summary of the relationship between normal cells,

adaptative cells, reversible injured cells and cell death
Relationship between normal, hypertrophic & injured myocyte
Cellular Responses to Injury
Nature and Severity of Injurious Stimulus Cellular Response
Altered physiologic stimuli: Cellular adaptations:
• Increased demand, increased trophic stimulation • Hyperplasia
• hypertrophy
• Decreased nutrients, stimulation • Atrophy
• Chronic irritation (chemical or physical) • Metaplasia
Reduced oxygen supply; chemical injury;infection Cell injury:
• Acute and self-limited • Acute reversible injury
• Progessive and severe (including DNA damage) • Irreversible injury ?
cell death
Necrosis
Apoptosis
• Mild chronic injury • Subcellular alterations
in various organelles
Metabolic alterations, genetic or acquired Intracellular
accumulations;
calcifications
Prolonged life span with cumulative sublethal injury Cellular aging
Cellular adaptation to stress
• Concept of Adaptation:
When cells encounter physiologic stresses or
pathologic stimuli from outside and inside of
body, they can alter themselves to achieve a
new steady state and preserve viability.
• All kinds of adaptation may be considered as
disorders of growth and differentiation
• Cellular adaptation can be considered as a
state between the normal, unstressed cell and
injured, overstressed cell.
Cellular adaptation to injury
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
• Subcellular responses to injury
• Intracellular accumulations
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
Atrophy
• Decrease in cell size
• Shrinkage in the size of the parenchymal cells
by loss of cell substances in a well developed
organ or tissue
• Acquired shrinkage of cells, tissues or organs.
• Simple atrophy (loss of cell size only)
• Numerous atrophy (loss of cell size and
number through apoptosis)
• Differentiation: aplasia, hypoplasia
Testis
Right: Atrophied Left: Normal
There are kidneys and ureters of a one-year-old boy.
The right kidney is hypoplastic and the left one with
a three-ureters abnormality.
Reasons for atrophy
• Decreased workload Disuse atrophy
• Loss of innervation Neuropathic atrophy
• Diminished blood supply Ischemic atrophy
• Absence of nutrition Undernourished atrophy
• Loss of hormone stimuli Endocrine atrophy
• Aging Senile atrophy
Atrophy of the brain in an 82-year-old male with atherosclerotic
disease, which is due to aging and reduced blood supply.
B, Normal brain of a 36-year-old male.
Note that loss of brain substance narrows the gyri and widens the
sulci.
Hydrocephalus
Hydrocephalus
Note the dilated ventricles,thinner grey and whine matter.
Nephrohydrosis
The renal calyces and renal pelvis are
There are some skeletal muscle fibers. The number of
cells is the same as before the atrophy occurred, but
the size of some fibers is reduced. In this case,
innervation of the small fibers in the center was lost.
This is a trichrome stain.
Atrophy
• The atrophied cells, tissue and organ have
– Reduction of physiologic functions
– Decreased synthesis
– Increased catabolism—increased protein
degradation through
Lysosomes digest the senescent organelles
(autolysis)
– If the number of cells decrease, there is
apoptosis (cell suicide), or programmed cell
death
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
Hypertrophy
• Definition: (briefly: increase in cell
size)
• An increase in the size of parenchymal
cells and consequently an increase in
the size of the organ.
No increase of cell
number in a purified
hypertrophy!
Hypertrophy
• Compensatory hypertrophy
– Mechanical stimuli---skeletal muscle of a
sportsman
– Increased workload---left ventricle
hypertrophy of systemic hypertension
– Decompensation---heart failure
• Endocrine hypertrophy
– Hormonal stimuli---pregnant uterus
---Cushing’s syndrome
Hypertrophy of left ventricle (centripetal hypertrophy) in
a patient with essential hypertension. Note the marked
thickened wall of ventricle.
a. Hypertrophy of the left ventricle
左心室肥大（左），正常心肌（中），肥大的心肌（右）
b. Normal myocardial fibers
c. Hypertrophic myocardial fibers
A pregnant uterus (right) and normal uterus (left)
Physiologic hypertrophy of the uterus during pregnancy.
L: gross appearance of a normal uterus and a gravid uterus.
Middle: small spindle-shaped uterine smooth muscle cells
From a normal uterus.
R: large, plump hypertrophied smooth muscle cells from
a gravid uterus.
Cushing’s syndrome resulted from adenoma of adrenal cortex
Hypertrophy
• Hypertrophic cells and organ with
– Increased function
– Increased synthesis of structural protein
– Induced by two types of signals
• Mechanical triggers----stretch
• Trophic triggers----activation of alpha-
adrenergic receptors
• Differentiate from
hyperplasia, pseudohypertrophy
The mechanism of hypertrophy
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
Hyperplasia
• Definition: (briefly, increase in cell number)
• An increase in the number of parenchymal
cells in an organ or tissue.
• Hyperplasia can occur with hypertrophy in
various tissue except muscles.
• Hyperplasia can be divided into
– Physiologic hyperplasia
• Hormonal: breast glandular epithelium at pregnancy
– Pathologic hyperplasia
• Compensatory: liver after partial resection
Hyperplasia of endometrium
in an adult woman with menorrhagia
Red bone marrow of blood donor
Hyperadrenalism
Goiter (absence of iodine)
Note the prostate is
nodular enlarged
Hyperplasia of
prostatic gland
Hyperplasia
• Hyperplasia is induced by stimulation of
hormonal or growth factors, cytokines and
chemokines through the signal transduction
pathway
• Hyperplasia can turn off when the organ
restores or the stimulus stops
• Continuous pathologic hyperplasia
constitutes a fertile soil for cancerous
proliferation
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
Metaplasia
• Definition: (briefly: change in cell type)
• A reversible change in which one adult cell
type is replaced by another adult cell type.
• This replacement is through hyperplasia of
“stem cell” or “undifferentiated cell”, so
metaplasia is actually an abnormal
hyperplasia.
• The significances of metaplasia are
– To be able to withstand the stress better
– To be able to transform into a cancerous
proliferation
Columnar to squamous metaplasia: Barrett metaplasia in
lower part of esophagus
Squamous metaplasia in bronchus in a heavy smoker
Squamous metaplasia of laryngeal respiratory
Epithelium in a heavy smoker
Intestinal metaplasia in a patient
with chronic atrophic gastritis. Note the goblet cells
Dysplasia:The normal squamous epithelium at the lef
transforms to a disorderly growth pattern. This is
farther down the road toward neoplasia.
Summary of adaptation
• Enlargement of an organ can result from
– Hypertrophy
– Hyperplasia
– Hypertrophy with hyperplasia
– pseudohypertrophy
– Edema
– Tumor
– Congestion
– Inflammation
• Shrinkage of an organ can result from
– Atrophy
– Aplasia and hypoplasia
• Hyperplasia persists only for so long as the
stimulus is applied. When it is removed, the
hyperplastic tissue tends to revert to its
normal size.
• Hyperplasia must be distinguished from
dysplasia and neoplastic proliferation.
• Metaplasia is an abnormal hyperplasia.
• It can become a malignant neoplasm.
• All kind of adaptation can be considered as
abnormal growth and differentiation
• Adaptation is the result of long time
persisted, but mild stimuli
• Most adaptations are reversible when the
stimulus is removed
Metaplasia Dysplasia Malignant
Summary of abnormal growth

tumor
Normal growth cells

adaptation
Simple Numerous Hypertrophy Hyperplasia

atrophy atrophy
Key words
Greek derivation:
• dys- bad, abnormal
• hyper- above, excessive
• hypo- below, deficient
• meta- beyond, between
• -plasia a forming
• -trophe nourishment
CELLULAR INJURY
Wenyan Zhang
Department of Pathology
West China School of Medicine
Sichuan University
March, 2018
Causes of cell injury
• Ischemia/hypoxia (e.g. heart attack)
• Chemical agents (toxins, acid, drugs)
– Active oxygen species: free radicals, oxidants,
electrophiles
• Infectious agents (bacterial, virus, parasite)
• Immunologic reactions (hypersensitivity)
• Genetic defects (e.g. Down’s syndrome)
• Nutritional imbalances (protein insufficiency)
• Physical agents (trauma, temperature)
• Iatrogenic causes
• Aging
Overview of Cell Injury and
Cell Death
Reversible cell injury
• Initially, injury is manifested as functional and
morphologic changes that are reversible if the
damaging stimulus is removed
• The hallmarks of reversible injury are reduced
oxidative phosphorylation, adenosine triphosphate
(ATP) depletion, and cellular swelling caused by
changes in ion concentrations and water influx
• These changes are called “ degenerations” in old
textbooks of pathology
Irreversible injury
• Irreversibly injured cells invariably undergo
morphologic changes that are recognized as cell
death
– Necrosis
– Apoptosis
• When damage to membranes is severe, lysosomal
enzymes enter the cytoplasm and digest the cell,
and cellular contents leak out, resulting in
necrosis
• Apoptosis, which is characterized by nuclear
dissolution without complete loss of membrane
integrity
Schematic representation of a normal cell and the changes in reversible and
irreversible cell injury.
Mechanisms of cell injury
• The cellular response to injurious
stimuli depends on the type of injury,
its duration, and its severity.
• The consequences of an injurious
stimulus depends on the type, status,
adaptability, and genetic makeup of
the injurious cell.
– Ischemia:
– Skeletal muscle: 2-3 hours normal
Cardiac muscle: 20-30 minutes death
Mechanisms of cell injury
• The vulnerable intracellular systems:
– Cell membrane integrity (ionic and osmotic balance)
– ATP generation
– Protein synthesis
– DNA
• Cellular function is lost far before cell death
occurs, and the morphologic changes of cell
injury ( or death) lag far behind both
General Biochemical Mechanisms
of cell injury
• ATP depletion
• Oxygen deprivation or generation of
reactive oxygen species
• Loss of calcium homeostasis
• Defects in plasma membrane permeability
• Mitochondria damage
of cell injury
• ATP depletion
• Defects in plasma membrane
permeability
of cell injury
• ATP depletion
permeability
Mechanism of ischemic and hypoxic injury
of cell injury
• ATP depletion
permeability
of cell injury
• ATP depletion
permeability
Cell mechanisms of injury
Free radicals/ reactive chemicals
O 2 Cell membrane
Normal
Metabolisms OH• Mitochondria
Inflammation Endo. Retic.
Radiation H2O2 DNA
Oxygen toxicity NO
Chemicals
Reperfusion injury
Detoxification
SOD/Catalase
Glutathione peroxidase/GSSG (Fenton reaction)
Vitamin E, C
Neutralization of free radicals
SOD
• 2O2 + 2H+ H2O 2 + O2
catalase
• 2H2O2 2H2O + O2
glutathione peroxidase
• 2OH• + 2GSH GSSH + 2H2O

glutathione reductase
of cell injury
• ATP depletion
permeability
of cell injury
• ATP depletion
permeability
of cell injury
• ATP depletion
permeability
of cell injury
• ATP depletion
permeability
of cell injury
• ATP depletion
permeability
of cell injury
• ATP depletion
permeability
Summary
• Any stimuli and stresses can result in cell injuries.
• The injurious consequences depend on not only the type

of injury, its duration, its severity, and also the type,
status, adaptability and genetic makeup of the injured
cell.
• Cell injury can be divided into reversible and irreversible.
• The loss of cell function is far before the cell death,

but the morphological visible changes appear far behind
the cell death.
Timing of biochemical and morphologic changes in cell injury.
Morphologic Changes of
Cell Injury

1 Introduction and Cell Adaptation

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Introduction to Pathology

Prof. Pao-Chaug Hou

Practice (48 credit hours)

• “Ask not what disease the

Sir William Osler (1849-1919)

CD10 Mum-1 BCL-6

GCET-1 FOXP-1 LMO-2

Hans 分型： GCB 型； Choi 分型： ABC 型； Tally 分型： GCB 型

L1100180, F/46, L1100259, M/15,

• The relationship between clinical

Adaptative cells Cell death

A summary of the relationship between normal cells,

Summary of abnormal growth

Normal growth cells

Simple Numerous Hypertrophy Hyperplasia

• 2OH• + 2GSH GSSH + 2H2O

• The injurious consequences depend on not only the type

• Cell injury can be divided into reversible and irreversible.

• The loss of cell function is far before the cell death,

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