Professional Documents
Culture Documents
1 Introduction and Cell Adaptation
1 Introduction and Cell Adaptation
Wenyan Zhang
Department of Pathology
West China School of Medicine
March.2018
Prof. QC Chen & Prof. Sadie C. F. Kiang
--
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”
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
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
Pathogenesis
Clinical manifestations Etiology
How to study pathology?
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
How to study pathology?
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
How to study pathology?
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
atrophy, necrosis
hypertrophy Reversible Lethal apoptosis
hyperplasia Reversible
metapllasia injured cells
intracellular accumulations,
degeneration
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
Cellular adaptation to injury
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
• Subcellular responses to injury
• Intracellular accumulations
Cellular adaptation to injury
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
• Subcellular responses to injury
• Intracellular accumulations
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
Summary of adaptation
• 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.
Summary of adaptation
• 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
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
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
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
Mechanism of ischemic and hypoxic injury
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
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
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
Cell Injury