Transcript Cellular Adaptations in Disease

Faculty of Medicine & Health Sciences
Semester 3
Pathology Course
P3
Cellular Adaptations in
Disease
Prof. James Lowe
5th October 1999
Cellular adaptations in disease
Overview

Adaptability of cells to an altered
environment
 Physiological

and pathological stimuli
Changes in growth pattern
 Hyperplasia,
hypertrophy, atrophy,
involution, metaplasia
Apoptosis
 Growth factors

 Role
in altered environment
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Why is this important?
Extremely common responses in disease
 Certain adaptations in growth act as a
fertile ground for the later development
of neoplasia - cancer formation…
 Nomenclature is used in clinical work.

Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Adaptability of cells to an
altered environment
Cells are constantly exposed to changes
in their environment
 Cells can adapt to acceptable changes in
their environment by modifying
metabolism or growth pattern
 Environmental changes can be
physiological or pathological

Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Examples of pathological
stimuli

Nutritional

Chemical agents

Immune

Infections

Endocrine

Anoxia

Physical agents

Genetic
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Metabolic regulation

Cells may adapt by metabolic regulation
 Induction
of enzyme
 Downregulation of enzyme
 Increased synthesis of product
 Reduced secretion of product

Metabolic adaptation is usually not
associated with morphological changes
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Cell stress response

The cell stress response allows cells to
survive pathological stimuli
 Housekeeping
genes switched off
 Cell stress genes switched on
Cells stress proteins are expressed in
cells (also called heat shock proteins)
 Cell stress proteins are cytoprotective

Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Cell stress proteins
Small cell stress proteins act as
molecular chaperones and prevent
misfolding of proteins
 Ubiquitin links to damaged proteins and
flags them for elimination by the cell
 Other groups of cell stress proteins have
roles in the nucleus.

Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Ubiquitin system
Free
ubiquitin
Activated
ubiquitin
proteosome
Degraded
protein
Damaged protein
Ubiquitinated protein
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Increased functional
demand

Increased functional demand can be met
by two main responses
 Increase
in cell size: hypertrophy
 Increase
in cell number: hyperplasia
These may occur independently or
together.
 Reflected by an increase in size and
weight of an organ
Faculty of Medicine & Health Sciences, October 1999

Cellular adaptations in disease
Physiological hypertrophy
Skeletal muscle hypertrophy in response to exercise
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Pathological hypertrophy
Myocardium in hypertensive heart disease
LV=left ventricle
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Pathological hypertrophy
Myocardium in hypertensive heart disease
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Physiological hyperplasia
Endometrium in the menstrual cycle
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Cellular adaptations in disease
Physiological hyperplasia
Pregnant uterus
Normal uterus
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Pathological hyperplasia
Normal skin
Hyperplasia after trauma
RP = rete peg
DP = dermal papilla
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Cellular adaptations in disease
Hyperplasia may be nodular
Hyperplasia may occur in a non-uniform
pattern in an organ or tissue - termed
nodular hyperplasia
 Examples include

 hyperplasia
of the prostate gland
 hyperplasia of the breast
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Nodular hyperplasia of
prostate
From a young
man showing
uniform texture
of gland
From an elderly
man showing
irregular
hyperplastic
nodules. This
would cause
obstruction
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Reduced demand for cell
activity

Reduction in the volume of a tissue is
termed atrophy
 reduction
in cell volume
 reduction in cell number
Cell loss is commonly replaced by either
adipose tissue or fibrous tissue
 Refelected in a reduced size and mass of
an organ

Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Common causes of atrophy
Denervation
 Immobilisation
 Reduced endocrine stimulation
 Ischaemia
 Ageing

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Cellular adaptations in disease
Pathological atrophy
A= atrophic skeletal muscle fibres
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Other causes of a small
organ other than atrophy
Hypoplasia: incomplete growth of an
organ
 Agenesis: complete failure of
development of an organ in
embryogenesis
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Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Physiological atrophy is
termed involution
Most instances of involution are the
result of withdrawal of an endocrine
stimulus
 Examples of involution

 breast
after cessation of lactation
 uterus after parturition
 thyroid after puberty
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Events in cell atrophy

Cell components are removed by
degradative systems
 cytosolic
proteolysis - ubiquitin system
 autophagy: elements enwrapped by internal
membrane systems and fused with the
lysosomal system

Residual lipid material may remain in
cells as a brown material termed
lipofuscin
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Reduction in cell number is
through programmed cell
death
Certain trophic signal to cells can lead to
a specific form of cell death
 Cell death is brought about by precise
metabolic systems
 The main type of programmed cell death
is termed apoptosis

Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Apoptosis
Normal cells are closely anchored by cell junctions
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Cellular adaptations in disease
Apoptosis: first stage...
Cells lose contact and round up. There is nuclear
condensation.
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Cellular adaptations in disease
Apoptosis next stage...
Apoptotic cell undergoes fragmentation to form apoptotic
bodies
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Cellular adaptations in disease
Apoptosis final event...
Apoptotic fragments are recognised by local cells and
phagocytes, are internalised, and degraded.
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Apoptosis biology

Cell death pathways exist in the cell
metabolism controlled by the action of
protease enzymes termed CASPASES
 DNA is
cleaved into fragments in between
nuceosomes by endonucleases
 Protein in cells is cross linked by
transglutaminases

Cell death pathways can be triggered by
several factors….
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Cellular adaptations in disease
Apoptosis triggers….
Surface receptor activation
 Surface membrane damage
 Damage to mitochondrial membranes
 DNA damage

Whether a cell lives or dies depends on the
balance between pro-apoptotic and antiapoptotic factors
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Change in cell differentiation
Cells may respond to stimuli by a change
in terminal differentiation
 This process is termed metaplasia

Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Examples of metaplasia
Bladder transitional epithelium (T) with metaplasia to
squamous epithelium (S) in response to a bladder stone…
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Cellular adaptations in disease
Example of metaplasia

Urothelium in response to stone
 transitional

Respiratory mucosa in response to
smoking
 Ciliated

epithelium to squamous
columnar epithelium to squamous
Connective tissue in response to trauma
 Collagenous
tissue to osseous tissue
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Growth factors
Growth factors and their receptors
control cell growth
 In disease, cell adaptations are controlled
by the action of growth factors linking to
nuclear transcription factors via
secondary messenger systems.

Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Summary
Cells adapt to altered environment
 Metabolic adaptation
 Cell stress response
 Changes in growth pattern

 Hyperplasia,
hypertrophy, atrophy,
involution, metaplasia

Growth factors, controlling proliferation
or cell death, play a key role in cell
adaptations in disease
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Links to future work...
Cell biology of apoptosis will be
continued when we consider neoplasia
and in MM course
 Cell biology of growth factors will be
continued when we consider healing and
repair and will also crop up in study of
neoplasia.

Faculty of Medicine & Health Sciences, October 1999