CELLULAR RESPONSE TO INJURY 1

Content
1. Causes of disease, Host-environment interaction in
disease, genetic factors, agents of injury, biochemical
mechanisms.
2. Reversible and irreversible changes of cell injury.
Types of cell death- necrosis and apoptosis, types of
necrosis.
3. Role of growth factors in differentiation, regeneration,
adaptations to physiological and pathological stimuli –
atrophy, hypertrophy, hyperplasia and metaplasia,
abnormal differentiation - dysplasia, anaplasia and
neoplasia.
Learning Outcomes
The student will be able to
1. Describe briefly the mechanisms of cell injury and list the
causes of cell injury.
2. Describe briefly the changes in an injured cell (reversible and
irreversible).
3. Define and describe necrosis and apoptosis and list their
causes with examples.
4. Define the growth, differentiation and regeneration, define
and describe with examples: hyperplasia, hypertrophy,
atrophy, metaplasia, dysplasia, anaplasia and neoplasia.
OVERVIEW :
cellular response to STRESS and NOXIOUS
STIMULI
Normal cell is confined to fairly narrow range of
function and structure by its state of metabolism,
differentiation and specialization;
It constantly adjusting to accommodate changing
demands and extracellular stresses;
Nevertheless it is able to handle physiological
demands, maintaining a steady state called
homeostasis.
 Pathology -
General Pathology :
◦ Common reaction of cells and tissues to injurious stimuli.
Study of Pathology and Medicine :
◦ Etiology : origin of diseases – underlying causes and
modifying factors, WHY disease occurs.
◦ Genetic (inherited mutations)
◦ Acquired (infections, chemicals, nutrition, etc)

◦ Pathogenesis : process in the development of diseases.

Sequence of cellular, biochemical and molecular events
following exposure to injurious agents. HOW disease
develops.
◦ Pathophysiology : the functional changes that accompany a
particular syndrome or disease; either hyper-/increased
production or hypo- / underproduction.
 Pathology
Study of Pathology and Medicine :
◦ Morphological changes: structural alteration in the
cells or tissues that are either characteristic of the
disease or diagnostic of an etiological processes.
◦ Functional derangement and clinical
manifestations: end results of genetic, structural and
biochemical changes in the cells and tissues.
◦ It leads to symptoms and signs of disease and its
progress and (clinical course and outcome).
CAUSES OF CELL INJURY

a) Excess or deficiency of oxygen

b) Physical agents
c) Chemical agents
d) Infection
e) Immunological reaction
f) Genetic derangements
g) Nutritional imbalance
h) Aging
 DIFFERENT TYPES OF CELLS
Labile cells Squamous epithelium of skin, mouth, vagina and cervix
Columnar epitheliu of intestinal tract, transitional
epithelium of urinary tract
Bone marrow cells
Stable cells Liver hepatocytes
Alveolar cells of lung
Epithelium of kidney tubules
Permanent cells Neurons
Skeletal and cardiac muscles
Adaptation
Definition-
Adaptation are reversible changes in size, number, phenotype,
metabolic activity or function of cells in response to changes in their
environment.

Severe physiological stresses and

some pathological stimuli;

Reversible functional and structural responses to cells;

more new, steady state is achieved,

cell continues to survive and function.

4 principal adaptive responses
Hypertrophy is an increase in the size of the cells resulting in
increase in the size of the organ;
Hyperplasia is an increase in cell number (becoz proliferation of
differentiated cells and replacement by tissue stem cells);
Hypertrophy and hyperplasia can occur together,
resulting in an enlarged hypertrophic organ.
Atrophy is decrease in the size and metabolic activity of the cells.
Metaplasia is a reversible change in which one adult cell type
(epithelial or mesenchymal) is replaced by an adult cell type.
TWO TYPES OF CELL INJURY
4 Principal adaptive responses
Adaptive response Adaptive changes Examples
Hypertrophy size of cells. Pathological or 1. Physiological
physiological enlargement of the
No of size uterus during pregnancy.
remains the same - Smooth muscles.
- Estrogen stimulation.

2. Weightlifter : striated
muscle hypertrophy –
physiological changes.

3. Pathological
hypertrophic of the
myocardium in
hypertension or aortic valve
diseases.
Examples of Hypertrophy

Pathological myocardial hypertrophy

Increase cardiac mass.
Increase protein synthesis by stretch
receptor stimulate growth factor.
Occur during pressure overload-post
myocardial infarction.
Reduced function-sometimes-usually
distorted heart and myocyte
Usually increase fibrosis
Increase risk of morbid outcome.
Examples of Hypertrophy
4 principal adaptive responses
Adaptive response Adaptive changes Examples
Hyperplasia no of cells. Pathological or Occurs @ cells that can
physiological replicate.

1. Physiological :
- hormonal
hyperplasia : female
breast @ puberty and
during pregnancy.

- compensatory
hyperplasia :
regeneration of residual
liver cells after partial
hepatectomy.

2. Pathological : caused
by excessive hormonal or
growth factor stimulation.
Benign prostatic hyperplasia
Hyperplasia of ducts
ATROPHY
Atrophy is also accompanied by increased autophagy giving the appearance of
increased autophagy vacuoles.

CAUSES OF ATROPHY
Atrophy is caused by decrease protein synthesis and increased protein degradation.

TWO types of atrophy

Pathological or physiological

Reduce of no of cells, with loss of cell functions.

However they are not dead.
Causes :
- Decreased workload due to :
1. Immobilization of a limb following fracture.
2. Denervation,
3. Diminished blood supply,
4. Inadequate nutrition,
5. Loss of endocrine stimulation,
6. Ageing
METAPLASIA
One adult cell type (eg. epithelial or mesenchymal) is replaced by another adult cell type.

PATHOLOGICAL OR PHYSIOLOGICAL
Often in response to chronic irritation.
If the stimulus that predispose to metaplasia persist, it may induce cancerous transformation.
May predispose to malignant transformation.

TWO TYPES
1. EPITHELIAL METAPLASIA
2. MESENCHYMAL METAPLASIA

1. Epithelium metaplasia
Squamous metaplasia
- Eg. chronic smoker
- Normal ciliated columnar epithelial cells of the trachea & bronchi are focally or widely
replaced by stratified squamous epithelial cells.
- Metaplastic squamous epithelium survive has survival advantages, however the protective
mechanism are lost.
- This may predispose to malignant transformation of the epithelium.

Metaplastic columnar epithelium – eg. chronic gastric reflux.

2. Mesenchymal metaplasia

Osseous metaplasia –bone formation

Fibroblast undergo osseous metaplasia to osteoblast or
chondroblast to produce bone or cartilage where it is
normally not encountered.
It is seen in
Soft tissue: scar
Muscle : myositis ossificans
 Squamous metaplasia of the cervix

Metaplasia is arise by reprogramming of stem cells to

differentiate along a new pathway rather than a
phenotypic change of already differentiated cells.
Metaplasia of normal columnar (left) to squamous epithelium (right)
in a bronchus (A) and histologically (B)
Examples of metaplasia
 ABNORMAL CELL GROWTH AND DIFFERENTIATION
DYSPLASIA

DEFINITION :
Is a premalignant condition characterized by increased
cell proliferation , the presence of cellular atypia and
decreased/altered differentiation.
It is an abnormal growth involving both
differentiation & maturation.
reversible only in early stage if the initial stimulus is
removed.
Severe dysplasia is reflection of underlying DNA
damage and may progress to frank malignancy unless it
is adequately treated.
May occur in tissue which has coincident metaplasia but
may develops without coexisting metaplasia.
Dysplasia in cervical squamous epithelium

Dysplastic squamous epithelium

3. Decreased differentiation and disordered
maturation

Ø Cell become more primitive appearance than

normal.
Ø E.g - In dysplastic squamous epithelium
Ø Loss of normal differentiation form basal cell to
flattened surface cells of the skin
Ø Dysplastic epithelial cells retain a resemblance to
basal cells as they move upward with failure of
keratinization.
(loss of epithelial polarity and maturation)
DIFFERENCE BETWEEN DYSPLASIA & NEOPLASIA
Neoplasia – characterized by abnormal, uncoordinated and excessive
cell proliferation , the growth persists after initiating stimulus has
been withdrawn.

1. Lack of invasiveness – basement membrane is intact.

- (both dysplasia & CA in situ )
- complete removal of dysplastic area – Curative
- In neoplasia – invasiveness (++)

2. Reversibility
- mild & moderate dysplasia – reversible
- severe dysplasia – irreversible
- All neoplasia - irreversible
Summary
Adaptation : reversible changes in the number,
size, phenotype, metabolic activity or function of
cells in response to changes in their environment.
◦Physiological adaptation are responses of cells
to normal stimulation by hormones or
endogenous chemical mediators.
◦Pathological adaptation are responses to stress
that allow cells to modulate their structure and
function and thus escape injury.
Summary
 Definition
Autolysis
the destruction of cells or tissues by their own enzymes,
especially those released by lysosomes.
Apoptosis is a pathway of cell death that is induced by a
tightly regulated suicide program in which cells destined to
die activate intrinsic enzymes that degrade the cells’ own
nuclear DNA and nuclear and cytoplasmic proteins.
Apoptotic cells break up into fragments, called apoptotic
bodies.
Heterolysis refers to apoptosis induced by hydrolytic
enzymes from surrounding (usually inflammatory) cells.
 Correctly match the following Answers

A Pregnant uterus Atrophy

B Barrett’s oesphogus hypertrophy

C Lactating breast hyperplasia

D Respiratory epithelium of Dysplasia

smoker

E BPH Metaplasia