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CELL INJURY, CELL

DEATH,AND
ADAPTATIONS
Syeda Rima Ishaq

WHAT IS

pathology?

PATHOLOGY
Pathos------

Suffering

Logos---------Study.

The study of suffering.

A
It

discipline that bridges clinical practice and basic science.

involves the investigation of the causes(etiology) of disease


as well as the underlying mechanisms (pathogenesis) that
result in the presenting signs and symptoms of the patient.

Cell Tissue Organ System

What is Cell Injury?


What is Cell Death?
How does injury cause death?

CELLULAR ADAPTATION
Cells

are the structural and functional


units of tissues and organs. They are
capable of adjusting their structure and
functions in response to various
physiological and pathological conditions.
This capability is called cellular
adaptation controlled by complex
molecular mechanisms.

Cellular Adaptation
Increased

Stress ------- Hyperplasia/Hypertrophy

Decreased

stress-------Atrophy

Change

in stressor------Metaplasia

Prolong

pathologic Hyperplasia----Dysplasia

Failure

of development------Aplasia

Decreased

cell production-----Hypoplasia

CELLULAR ADAPTATION
Cellular

adaptations include:
Atrophy--shrinkage of cells
Hypertrophy--increase in the size of cells which results
in enlargement of the organs
Hyperplasia--increased number of cells in an organ or
tissue
Metaplasia--transformation or replacement of one adult
cell type with another

Cell Adaptation to Injury


Five Cellular Adaptations to Injury:
1. Atrophy
2. Hypertrophy
3. Hyperplasia
4. Metaplasia
5. Dysplasia

Atrophy:

shrinkage of cells; classified as:

Physiologic--due

to decreased work load


(e.g., decreased size of uterus following
child birth, or disease)

Pathologic--primarily

due to denervation
of muscle, diminished blood supply,
nutritional deficiency

Cell Adaptation to Injury

1) Atrophy

It means Decrease or shrinkage in cellular size.


That is either Physiological or Pathological
Pathologic atrophy occur due to in :
Workload
Pressure
Use
Blood supply
Nutrition
Hormonal Stimulation
Nervous Stimulation
Atrophy is generally a reversible process, except for
atrophy caused by loss of nervous innervations to a
tissue.
Causes of atrophy include prolonged bed rest, disuse
of limbs or tissue, poor tissue nutrition and ischemia.

Atrophy
There

are some muscle fibres


here that show atrophy.
The number of cells is the
same as before the atrophy
occurred, but the size of
some fibres is reduced.
This is a response to injury by
"downsizing" to conserve the
cell.

Hypertrophy Increase

in the size of cells which results in


enlargement of the organs.
It is mostly seen in cells that cannot divide, such as:
skeletal muscle (pumping iron),
cardiac muscle (hypertension).
These changes usually revert to normal if the cause is
removed.
Hypertrophy is mediated by different mechanisms.

Cell Adaptation to Injury

Increase in cell size and tissue mass.

Occurs when a cell or tissue is

3) Hypertrophy

exposed to an increased workload.

Occurs in tissues that cannot

increase cell number as an adaptive response.

Hypertrophy may be :

normal physiologic response, such as the increase in muscle mass that


is seen with exercise

pathologic as in the case of the cardiac hypertrophy that is seen with


prolonged hypertension.

or compensatory process, when one kidney is removed, for example,


the remaining kidney hypertrophies to increase its functional capacity.

Hypertrophy
This

is cardiac hypertrophy
involving the left ventricle.
The number of myocardial
fibres does not increase, but
their size can increase in
response to an increased
workload, leading to the
marked thickening of the left
ventricle in this patient with
systemic hypertension.

Cell Adaptation to Injury2) Hyperplasia

Increase in number of cells resulting from increased rate of cellular


division.

It is either:

Physiologic process, as in the breast and uterine hyperplasia that


occurs during pregnancy,

Pathologic: such as Benign Prostatic Hyperplasia (BPH) and gingival


hyperplasia (overgrowth of gum tissues) that maybe seen in certain
patients receiving the drug phenytoin.

or compensatory mechanism: for example, when a portion of the


liver is surgically removed, the remaining hepatocytes (liver cells)
increase in number to preserve the functional capacity of the liver .

Hyperplasia

The prominent folds of


endometrium in this uterus opened
to reveal the endometrial cavity
are an example of hyperplasia.
Cells forming both the endometrial
glands and the stroma have
increased in number.
As a result, the size of the
endometrium has increased.

Cell Adaptation to Injury

4) Metaplasia

The conversion of one cell type to another


cell type that might have a better chance of
survival under certain circumstances.
Metaplasia occurs in response to chronic irritation or inflammation.
An example of metaplasia is:
in the respiratory passages of chronic cigarette smokers, following
years of exposure to irritating cigarette smoke, the ciliated columnar
epithelium lining the respiratory passages gradually converts to stratified
squamous epithelium which although be better to survive to the cigarette
smoke, they lack the cilia of the columnar epithelial cells that are necessary
for clearing particulates from the surfaces of the respiratory passages.

Metaplasia:

Transformation or replacement of one adult cell type


to another adult cell type
(e.g., the change from columnar to squamous cells
in respiratory tract, from squamous to columnar in
Barrett esophagitis).
Metaplasia also occurs in mesenchymal tissue
(e.g., formation of bone in skeletal muscle).
Metaplastic changes usually result from chronic
irritation.
Metaplastic changes seem to precede the
development of cancer, in some instances.
Metaplasia is thought to arise from reprogramming of
stem or undifferentiated cells that are present in
adult tissue.

Metaplasia

Metaplasia of laryngeal respiratory


epithelium has occurred here in a smoker.
The chronic irritation has led to an
exchanging of one type of epithelium (the
normal respiratory epithelium at the
right) for another (the more resilient
squamous epithelium at the left).
Metaplasia is not a normal physiologic
process and may be the first step toward
neoplasia.

Cell Adaptation to Injury

5) Dysplasia

A derangement of cell growth that leads to tissues with cells of


varying size, shape and appearance.

Generally occurs in response to chronic irritation and


inflammation.
Dysplasia may be a strong precursor to cancer in certain instances
such as in the cervix or respiratory tract. However, dysplasia is an
adaptive process and as such does not necessarily lead to cancer. In
many cases, the dysplastic cells revert to their former structure and
function.

Dysplasia

This is dysplasia. The normal


cervical squamous epithelium has
become transformed to a more
disorderly growth pattern, or
dysplastic epithelium.
This is farther down the road
toward neoplasia, but dysplasia is
still a potentially reversible
process.

Cell Injury
If

the cells fail to adapt under stress, they undergo


certain changes called cell injury. The affected cells
may recover from the injury (reversible) or may die
(irreversible).
Cell injury results
When cells are stressed so severely that no
longer to able to adapt. Or
When cells are exposed to inherently damaging
agent. Or
Suffer from intrinsic abnormality.

CELL INJURY

Causes of cell injury heterogeneous, range from gross mechanical


external causes to mild endogenous causes as genetic lack of
enzymes etc.
Normal cell is confined to relatively narrow range of functions
and structure by its genetic program to handle normal physiologic
demands

homeostastatic steady state

Cells react to adverse influence by

adapting

sustaining reversible injury

suffering irreversible cellular injury- cell death

Causes of Cell Injury


oxygen

deprivation (anoxia)
physical agents
chemical agents
infections agents
immunologic reactions
genetic defects
nutritional imbalances
Aging
Hypoxia: due to
ischemia(Decreased blood flow)
Low partial pressure of Oxygen in the blood(hypoxemia)
Decreased oxygen carrying capacity in the blood

IMPORTANT TARGETS OF CELL INJURY


Aerobic

respiration
ATP depletion or decreased synthesis.
Cell membranes - plasma membranes, mitochondrial,
lysosomal and other organelle membranes.
Protein synthesis.
Cytoskeleton.
Genetic apparatus.

Biochemical

1. ATP

mechanisms in cell injury:

depletion
2. Mitochondrial damage
3. Plasma membrane permeability
defect
4. Oxygen free radicals
5. Ca++ influx to the cell

ATP DEPLETION - HYPOXIA/ISCHAEMIA

Mitochondria - reduced oxidative phosphorylation.

Cell membrane - Stop of ATP-dependent Na-pump. Resulting in increase Na+ and

water, and loss of K+. The end result is cell swelling.

Endoplasmic reticulum dilates, the cell swells, blebs appear.

Anaerobic glycolysis results in production of lactic acid and drop of pH

Failure of the calcium pump leads to influx of Ca++ into the cell, activate various
enzymes to the detriment of the cell(cell death).

Later there is swell in of the rough endoplasmic reticulum, RER loses ribosomes
and protein synthesis falls - structural proteins (membranes,cytoskeleton) and
enzymes.

Misfolded proteins lead to the unfolded protein response which may further injure
the cell.

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 4 April 2005 06:11 PM)
2005 Elsevier

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 4 April 2005 06:11 PM)
2005 Elsevier

ISCHAEMIA/REPERFUSION INJURY

If cells are reversibly injured due to ischaemia, complete recovery occurs


following restoration of blood flow.

However, reperfusion can result in more damage including cell death.

This is due to incompletely metabolized products producing reactive oxygen


species on re-introduction of oxygen
especially
loss

damaging to mitochondria;

of anti-oxidants during ischaemia;

inflow

of calcium with the renewed blood flow;

recruitment

of leukocytes to the injured area.

Reperfusion injury is especially important in ischaemic damage to the heart


and brain and in organ transplantation.

CHEMICAL & BIOLOGICAL AGENTS

Chemical agents - direct effects, e.g.

cyanine on cytochrome oxidase, HgCl


on sulphydryl groups of proteins, ricin
on ribosomes, cytotoxic effects of
chemotherapy & antibiotics.
-indirect

effects via free radicals.

Cell injury

Reversible cell injury denotes pathologic


changes that can be reversed when the stimulus
is removed and the cellular injury has been
mild. Cell injury is reversible- up to certain
point.

Irreversible cell injury denotes pathologic


changes that are permanent and cause cell
death, cannot be reversed to normal state

Cell death

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