Cell adaptation

Shah Faisal
Lecturer Kmu
 Definition
In response to environmental stress the change in
cell shape, size, pattern of growth and metabolic
activity in order to escape and protect themselves
from injury is called cellular adaptation.
OR
The group of changes within cell in response to
environmental stress is called cellular adaptation.
OR
Cellular adaptation refers to those adjustments that
a cell makes in response to alterations in the
environment in which it must live.
 Cellular Adaptation
• Permits survival and maintenance of cell
function
• May alter differentiation of genes
enabling a cell to change size or form.
– Is a normal adaptive response to an
appropriate stimulus
• Abnormal cellular changes may also
occur
 Cellular Responses to Stress and Noxious Stimuli

The normal cell is confined to a fairly narrow

range of function and structure by its genetic
programs of metabolism, differentiation, and
specialization; by constraints of neighboring
cells; and by the availability of metabolic
substrates.
It is nevertheless able to handle normal
physiologic demands, maintaining a steady
state called homeostasis.
 Normal Cell Growth
Labile Cells: Proliferate continuously, short life span, and
high regenerative capacity e.g. Bone marrow stem cells,
Epidermal cells of the skin, Gut epithelium.
• Stable Cells: These divide infrequently but
can regenerate when cells are lost. e.g.
hepatocytes.
• Permanent Cells: They divide only in fetal life and can
not be replaced when lost .Repair occurs when dead cells are
removed & matrix (Collagen) fills gaps. e.g. Neurons,
cardiac.
Stages in the cellular response to stress and injurious stimuli.
 Introduction to Cellular Adaptations

Stresses of different types may induce changes in cells

and tissues other than adaptations, cell injury, and
death. Cells that are exposed to sub lethal or chronic
stimuli may not be damaged but may show a variety of
sub cellular alterations.
Metabolic derangements in cells may be associated with
intracellular accumulations of a number of substances,
including proteins, lipids, and carbohydrates.
Calcium is often deposited at sites of cell death, resulting
in pathologic calcification.
Finally, cell aging is also accompanied by characteristic
morphologic and functional changes.
 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.
Various Types of Adaptations

● cells may undergo various adaptations in physiological and pathological

conditions

● controlled by complex molecular mechanisms

● common types of cellular adaptations

1. atrophy
2. hypertrophy
3. hyperplasia
4. metaplasia
5. dysplasia
6. intracellular accumulations
7. pathological calcifications
a. dystrophic calcification
b. metastatic calcification
 ATROPHY
• Shrinkage in the size of the cell by loss of cell
substance is known as atrophy.
– reduction in cell volume
– reduction in cell number
• Atrophy can be physiologic or pathologic.
• Physiologic atrophy is common during early
development.
• It represents a form of adaptive response and may
culminate in cell death.
• When a sufficient number of cells are involved,
the entire tissue or organ diminishes in size, or
becomes atrophic.
 Atrophy
(cells shrink)

•D/t 🡣 workload or adverse

environmental conditions
– Is adaptive and reversible
– results in a decrease
in cell size
Unilateral
• Types
– Disuse atrophy (paralysis)
– Degeneration atrophy (MS)
– Ischemic atrophy (kidney, heart)
– Malnutrition atrophy
(starvation)
– Loss of endocrine
stimulation (uterine, breast) Bilateral Atrophy
 • Cellular Adaptations

Size Number Type

Atrophy Hypertrophy Hyperplasia Metaplasia Dysplasia

1. Disuse
2. Loss of
endocrine
stimulation Intracellular Calcifications
Accumulations
3. Denervation
4. Inadequate
nutrition Dystrophic Metastatic
5. Ischemia
 Atrophy Cont’d

• Less mitochondria
• Less ER
• Fewer myofilaments
The metabolic rate is reduced;
• Less amino acid uptake
• Less oxygen consumption
• Less protein synthesis
 Mechanism of Atrophy

• To affect the balance between protein synthesis

and degradation.
• Increased protein degradation probably
plays a key role in atrophy.
• Lysosomes contain acid hydrolases and other
enzymes that degrade proteins from the
extracellular environment and the cell surface
as well as some cellular components.
– cytosolic proteolysis
– autophagy: elements enwrapped by internal
membrane systems and fused with the lysosomal
system
Autophagy
Pathological Atrophy

A= atrophic skeletal muscle fibres

Denervation Atrophy
 Physiological Atrophy is Termed Involution

• Most instances of involution are the result of

withdrawal of an endocrine stimulus
Examples :
– breast after cessation of lactation
– uterus after parturition
– thyroid after puberty
Bring more example for the next class??????
A, Atrophy of the brain in an 82-year-old male with atherosclerotic
disease. Atrophy of the brain is due to aging and reduced blood supply.
The meninges have been stripped. B, Normal brain of a 36- year-old
male. Note that loss of brain substance narrows the gyri and widens the
sulci.
 HYPERTROPHY

● increase in the size of cells which results in

enlargement of the organs
● mostly seen in cells that cannot
divide, i.e.,
• skeletal muscle (strength training)
• cardiac muscle (hypertension)
●changes usually revert to normal if the stimulus
is removed
● mediated by different mechanisms
 Hypertrophy

Physiologic Pathologic

Exercise Adaptive Compensatory

 Physiological Causes of Hypertrophy

Examples:
• Increased work load ,Body builders and athletes
: (strength training).
• Hormone stimulation—pregnant uterus

• changes usually revert to normal if the

stimulus is removed
• mediated by different mechanisms

Bring more example for the next class??????

 Pathological Causes of Hypertrophy

• Cardiac muscle (hypertension)

• Physical hypertrophy obstruction ---bladder

smooth in outflow obstruction caused by an
enlarged prostate gland.
• In the heart, the stimulus for hypertrophy is usually
chronic hemodynamic overload, resulting from
either hypertension or faulty valves.
• The massive physiologic growth of the uterus
during pregnancy is a good example of hormone-
induced increase in the size of an organ that results
from both hypertrophy and hyperplasia.
• The cellular hypertrophy is stimulated by
estrogenic hormones acting on smooth muscle
estrogen receptors, eventually resulting in
increased synthesis of smooth muscle proteins and
an increase in cell size
 Mechanism

• The increased size due to synthesis of more

structural components.
• cells capable of division may respond to
stress by undergoing both hyperplasia and
hypertrophy, whereas in nondividing cells
hypertrophy occurs. Find Example
• Nuclei in hypertrophied cells may have a
higher DNA content than in normal cells,
probably because the cells arrest in the cell
cycle without undergoing mitosis.
 HYPERPLASIA
• increased number of cells in an organ or tissue

• may sometimes co-exist with hypertrophy

• classified as:
•
– physiologic

- hormonal (e.g., breast and uterus during

normal menstrual cycle and pregnancy)

- compensatory (regeneration of liver following

partial hepatectomy or wound healing)

– pathologic
- excessive hormonal stimulation (BPH)
 HYPERPLASIA (cont)
• May be a PHYSIOLOGICAL response and
occur with hypertrophy (🡡 in both cell size & number)
– Hyperplasia is important in wound healing
• May also be a non-physiologic
hyperplasia
– Seen in prostatic hypertrophy (BPH), endometrial
hyperplasia
d/t increased hormone stimulation, or thyroid enlargement
Goiter –
thyroid
hyperplasia
Benign Prostatic
Hypertrophy/Hyperplasia (BPH) –
can cause difficulty
 Hyperplasia seen in finger
warts: epidermal hyperplasia d/t
viral s t i mu l a t i o n

Verrucae vulgaris – common

warts

Plantar
warts -
🡑 in # of
epiderm
al cells

(🡑 DNA synthesis and mitotic

division)
 Causes of Hyperplasia
• Hyperplasia is generally caused by increased local
production of growth factors
• increased levels of growth factor receptors on
the responding cells,
• or activation of particular intracellular
signaling pathways.
• All these changes lead to production of transcription
factors that turn on many cellular genes, including
genes encoding growth factors, receptors for growth
factors, and cell cycle regulators, and the net result is
cellular proliferation.
Hyperplasia can be physiologic or pathologic.
HYPERPLASIA
Physiologic hyperplasia can be divided into:

1. hormonal hyperplasia
2. compensatory hyperplasia

Pathologic
 Hyperplasia cont’d

Physiologic
1. hormonal hyperplasia, which increases the
functional capacity of a tissue when needed.
Examples------
– 2. compensatory hyperplasia, which increases
tissue mass after damage or partial resection.
Examples------
Pathol
ogic
Exam
ple
s---
---
 METAPLASIA
• transformation or replacement of one adult cell type
to another adult cell type
Examples------
• also occurs in mesenchymal tissue (e.g.,
formation of bone in skeletal muscle)

• metaplastic changes usually result from

chronic irritation

• changes seem to precede the development of cancer,

in some instances

• thought to arise from reprogramming of stem or

undifferentiated cells that are present in adult
tissue
 METAPLASIA
 One cell type is replaced by another
 May predispose to cancer
 Involves reprogramming of undifferentiated stem cells

 Allows to cells to better survive in a hostile

environment
 Is REVERSIBLE
 Is a response to chronic irritation and
inflammation
 METAPLASIA
• Cells that are normally columnar
or stratified may change to
squamous.
• – Examples:
With continued smoke exposure, ciliated columnar cells are
changed to stratified squamous cells
– Cervical cells change when exposed to STDs or HPV

• Think metamorphosis or change from

–one form toexposure
Continued anothermay predispose to cancerous
transformations.
Ciliated columnar Stratifiied squamous
cells cells
 DYSPLASIA

• deranged cell growth that results in cells

that vary in size,shape and organization.
• minor degrees are associated with irritation
or inflammation
• most commonly associated
with respiratory tract or uterine cervix
• potentially reversible
• often a precursor for cancer
 Anaplasia
• Cells differentiate to a more IMMATURE
or embryonic form.
• Malignant tumors are characterized by
anaplastic cell growth.

Ovarian cancer cells

dividing
 Cellular Infiltrations
carbon, triglycerides
• Carbon can accumulate via inhaled coal dust. Can cause
black lung disease (pneumonconiosis)
• Organs enlarged, i.e., MEGALY“ ”
– Ex. spleenomegaly, hepatomegaly

hepatomegaly
• Diseases d/t cellular accumulations MAY BE
REVERSIBLE if d/t a correctable systemic disorder
– Example: elevated triglyceride levels can result in a “FATTY”
liver.
• This may reverse when triglyceride level is lowered with medication
Summary:
Cellular
Changes

🡣
Then anaplasia/neoplasia