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Introduction to Pathology. By Gandi Li Department of Pathology West China Medical School Feb,2003. Where there is love of medicine, there is love of humankind. -- Hippocrates (460-377 BC). The most common diseases in developing countries.

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introduction to pathology

Introduction to Pathology

By Gandi Li

Department of Pathology

West China Medical School

Feb,2003

the most common diseases in developing countries
The most common diseases in developing countries
  • Infectious diseases (viral hepatitis, tuberculosis, bacterial pneumonia, bacterial diarrheas, AIDS, et al)
  • Atherosclerosis and hypertension
  • Cancer
  • Emphysema and chronic bronchitis
  • What happens in Nepal?
slide4
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.
  • Now more and more people know many diseases are lifestyle-related.
  • Pathology is a bridge between medicine and basic sciences formedical students.
  • Pathology is also one of the most important methods to diagnose disease in clinical practice.
pathology involves
Pathology involves
  • Etiology (causes of diseases,Why?)
  • Pathogenesis (mechanisms, How?)
  • Pathological changes (lesions, What?)
    • Morphological changes (anatomical pathology)
    • Functional changes (pathophysiology)
  • Clinical manifestations (signs and symptoms)
  • Sequelae (healing, complications, death)
branchs of pathology
General pathology

cell injury

tissue repair

hemodynamic disorders

inflammation

tumor

Systemic pathology

the blood vessels and the heart

the respiratory system

the digestive system

the urinary system

the male and female genital system

the nervous system

the endocrine system

Branchs of pathology
goal of pathology for medical students
GOAL of PATHOLOGY for MEDICAL STUDENTS
  • Be able to understand and analyze the relationship between pathologic changes and clinical manifestations.
  • Be able to take a clinical history and order tests logically.
  • Be able to develop a correct diagnosis.
  • Be able to communicate with professionals and patients.
  • Does become a physician or a pathologist? Physician or surgeon mostly.
what does a pathologist do
What does a PATHOLOGIST do?
  • SURGICAL PATHOLOGY
    • Interpret biopsies (e.g., skin, breast, gastrointestinal tract)
    • Evaluate surgical resection specimens (e.g., colectomy, nephrectomy, mastectomy)
    • Frozen sections (intra-operational rapid diagnosis)
what does a pathologist do1
What does a PATHOLOGIST 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
    • Final diagnosis, forensic pathology--criminal investigation
how to study pathology
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)
how to study pathology1
How to study pathology?
  • The key for studying pathology:

Characteristic

morphologic lesions (lesions)

Functional

Changes

(Pathophysiology)

Pathogenesis

Etiology

Clinical manifestations

how to study pathology2
How to study pathology?

Approach to good result:

  • Lectures and textbooks
  • Laboratory practice: gross specimen and glass slides
  • Clinicopathologic conference (CPC)
  • Autopsy demonstration (real or video)
  • Recommend internet web sites:

http://www-medlib.med.utah.edu/webPath/webpath.html

slide13

Observation of gross specimen:

a hypertrophic heart (left) and a normal heart (right)

summary of introduction
Summary of introduction
  • The terms
    • disease pathology general pathology
    • lesion pathologist surgical pathology
  • The roles of pathology in medical education and clinical practice
  • How to study pathology
    • Uebung machts Master. (Practice trains master)
    • Arbeit machts Spass! (Work brings happy!)
slide20
“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 (Canadian Physician)

cell injury adaptation and death
Cell Injury, Adaptation and Death
  • Overview of cell injury
  • Causes of cell injury
  • Mechanisms of cell injury
  • Cellular adaptation to injury
  • Reversible and irreversible cell injury
  • Programmed cell death---- apoptosis
  • Cellular aging
overview of cell injury
Overview of cell injury
  • Homeostasis requires functional cooperation in widely distributed cells.
slide23

Normal cells

homeostasis

Lethal

Reversible

Reversible

Cell death

Adaptative

cells

necrosis

apoptosis

atrophy,

hypertrophy

hyperplasia

metapllasia

Reversible

Reversible

injured cells

Lethal

intracellular accumulations, degeneration

A summary of the relationship between normal cells,

adaptative cells, reversible injured cells and cell death

slide24

The relationship between cellular function, cell death and

the morphologic changes of cell injury.

causes of cell injury
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 (Down’s syndrome)
  • Nutritional imbalances (protein insufficiency)
  • Physical agents (trauma, temperature)
  • Aging
mechanisms of cell injury
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
slide28

Cell mechanisms of injury

Free radicals/ reactive chemicals

O2

OH•

H2O2

NO

Cell membrane

Mitochondria

Endo. Retic.

DNA

Normal

metabolisms

Detoxification

SOD/Catalase

Glutathiole peroxidase/GSSG

Vitamin E, C

neutralization of free radicals
Neutralization of free radicals

SOD

  • 2O2 + 2H+ H2O 2 + O2

catalase

  • 2H2O2 2H2O + O2

glutathione peroxidase

  • 2OH• + 2GSH GSSH + 2H2O

glutathione reductase

summary
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.
cellular adaptation to injury
Cellular adaptation to injury
  • 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/or differentiation
  • Cellular adaptation can be considered as a state between the normal, unstressed cell and injured, overstressed cell.
atrophy
Atrophy
  • Definition: (briefly, decrease in cell size)

Shrinkage in the size of the parenchymal cells by loss of cell substances in a well developed organ or tissue is known as atrophy. Or:

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
slide36

Testis:

Right: Atrophied Left: Normal

slide37

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.

atrophy1
Atrophy
  • The reasons of atrophy:
    • Decreased workload disuse atrophy
    • Loss of innervation neuropathic atrophy
    • Diminished blood supply ischemic atrophy

press atrophy

    • Absence of nutrition undernourished atrophy
    • Loss of hormone stimuli endocrine atrophy
    • Aging senile atrophy
slide39

Brain atrophy in an old patient with arteriosclerosis. Note the

widened sulci and narrow convolutions.

slide40

Brain atrophy in a patient with Alzheimer’s disease. The gyri are narrowed and the sulci widened toward to frontal pole.

slide41

Hydrocephalus (left) and nephrohydrosis (right)

Note the dilated ventricles and thinner grey and

whine matter. The renal calyces and renal pelvis are dilated too.

slide42

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.

atrophy2
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
hypertrophy
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!

hypertrophy1
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

slide46

Hypertrophy of left ventricle (centripetal hypertrophy) in

a patient with essential hypertension.Note the marked

thickened wall of ventricle.

slide47

Hypertrophy of the left ventricle

  • Normal myocardial fibers
  • Hypertrophic myocardial fibers
slide49

Physiologic hypertrophy of the uterus during pregnancy.

Left: gross appearance of a normal uterus and a gravid uterus.

Middle: small spindle-shaped uterine smooth muscle cells from

A normal uterus.

Right: large, plump hypertrophied smooth muscle cells from

a gravid uterus.

hypertrophy2
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

hyperplasia
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
slide54

Examples of hyperplasia:

Red bone marrow of blood donor

slide56

Examples of hyperplasia:

Goiter (absence of iodine)

slide57

Note the prostate is

nodular enlarged

Hyperplasia of

prostatic gland

hyperplasia1
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
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
slide64

Intestinal metaplasia

in a patient with

chronic atrophic

gastritis

Note the goblet

cells

slide65

This is dysplasia. The normal squamous epithelium at the left

transforms to a disorderly growth pattern at the right. This is

farther down the road toward neoplasia.

summary of adaptation
Summary of adaptation
  • Enlargement of an organ can result from
    • Hypertrophy
    • Hyperplasia
    • Hypertrophy with hyperplasia
    • Pseudohypertrophy (actual atrophy)
    • Edema
    • Tumor
    • Congestion
    • Inflammation
summary of adaptation1
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 adaptation2
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/or differentiation
  • Adaptation is the result of long time persisted, but mild stimuli
  • Most adaptations are reversible when the stimulus is removed
slide69

Metaplasia

Dysplasia

Malignant tumor

Summary of abnormal growth

Normal cells

adaptation

Simple

atrophy

Numerous

atrophy

Hypertrophy

Hyperplasia

learn words
Learn words

Greek derivation:

  • dys- bad, abnormal
  • hyper-above, excessive
  • hypo-below, deficient
  • meta- beyond, between
  • -plasia a forming
  • -trophe nourishment
requirements
Requirements
  • The overview of cell injuries
  • The main mechanisms of cell injury
    • Ischemia/hypoxia free radicals
  • Concepts and recognition of lesions
    • Adaptation Atrophy Hypertrophy
    • Hyperplasia Metaplasia
  • Give samples of various forms of adaptation and understand their significances