General Pathology

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, et al)
Atherosclerosis and hypertension
Cancer
Emphysema and chronic bronchitis
What happens in Nepal?
402 General Pathology (Theory)02 100
Cell Injury and Cellular Adaptations: Normal Cell structure and function,
Cell Injury, types of cell injury, etiology of cell injury, morphology of cell
injury, cellular swelling. Cell death; autolysis, necrosis, apoptosis &
gangrene.Cellular adaptations; atrophy, hypertrophy, hyperplasia and
dysplasia.Inflammation: Acute inflammation; vascular, cellular,
inflammatory cells. Chronic Inflammation; general features,
granulomatous inflammation, tuberculoma.

Haemodynamic Disorders: Oedema, hyperemia, congestion,

haemorrage, circulatory disturbances, thrombosis, ischaemia& infarction.
Neoplasia: Definition, how does it differ from hyperplasia, difference
between benign tumor and malignant tumor.Healing: Definition, different
phases of healing, factors influencing wound healing.
Course No. Title
Credit Hours Marks
MLT 403 General Pathology (Practical)01
100
1. Components & setting of the Compound microscope.
2. Focusing of object. 3. Use of low &
high power objectives of microscope.
4. Use of oil immersion lens. 5. Care and
Maintenance of the microscope.
6. Different types microscopy 7. Dark field
microscopy
8. Fluorescence Microscopy 9. Electronic
Microscopy in brief.
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 for medical students.
Pathology is also one of the most important
methods to diagnose disease in clinical
practice.
 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 Systemic pathology
 cell injury  the blood vessels and
 tissue repair the heart
 hemodynamic  the respiratory system
disorders  the digestive system
 inflammation  the urinary system
 tumor  the male and female
genital system
 the nervous system
 the endocrine system
 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?

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 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?
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 pathology?
The key for studying pathology:
Functional
Changes
Characteristic (Pathophysiology)
morphologic lesions (lesions)

Pathogenesis
Clinical manifestations Etiology
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
Observation of gross specimen:
a hypertrophic heart (left) and a normal heart (right)
Gross observation of a nutmeg liver and mircoscopic changes
Cancer cells in ascites of a patient with gastric carcinoma
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!)
A famous painting about autopsy by Rhunbrant in 18 century
“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
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
Homeostasis requires functional
cooperation in widely distributed cells.
 Normal cells
homeostasis
Reversible Lethal

Reversible
Adaptative Cell death
cells necrosis
atrophy, Reversible apoptosis
hypertrophy Reversible Lethal
hyperplasia injured cells
metapllasia
intracellular accumulations,
degeneration
A summary of the relationship between normal cells,
adaptative cells, reversible injured cells and cell death
The relationship between cellular function, cell death and
the morphologic changes 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
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
 Cell mechanisms of injury
Free radicals/ reactive chemicals
O 2 Cell membrane
OH• Mitochondria
Normal Endo. Retic.
metabolisms H2O2 DNA
NO
Detoxification

SOD/Catalase
Glutathiole peroxidase/GSSG
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
 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
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
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
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.
 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
Brain atrophy in an old patient with arteriosclerosis. Note the
widened sulci and narrow convolutions.
Brain atrophy in a patient with Alzheimer’s
disease. The gyri are narrowed and the sulci
widened toward to frontal pole.
Hydrocephalus (left) and nephrohydrosis (right)
Note the dilated ventricles and thinner grey and
whine matter. The renal calyces and renal pelvis are dilated too.
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
 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
b. Normal myocardial fibers
c. Hypertrophic myocardial fibers
A pregnant uterus (right) and normal uterus (left)
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.
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
 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
Examples of hyperplasia:

Red bone marrow of blood donor

Examples of hyperplasia:

Hyperadrenalism
Examples of hyperplasia:

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
 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
Squamous metaplasia in bronchus in a heavy smoker
Squamous metaplasia of laryngeal respiratory epithelium in a
heavy smoker
Columnar to squamous metaplasia: Barrett metaplasia in
lower part of esophagus
Intestinal metaplasia
in a patient with
chronic atrophic
gastritis
Note the goblet
cells
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
Enlargement of an organ can result from
 Hypertrophy
 Hyperplasia
 Hypertrophy with hyperplasia
 Pseudohypertrophy (actual atrophy)
 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/or 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 cells
adaptation

Simple Numerous Hypertrophy Hyperplasia

atrophy atrophy
 Learn words
Greek derivation:
dys- bad, abnormal
hyper- above, excessive
hypo- below, deficient
meta- beyond, between
-plasia a forming
-trophe nourishment
 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
Thank you for your
attention!