Cell Adaptation

Gul Fatima/R.Ph
Lecturer, SICP
 Cellular Adaptations
• Adaptations are reversible changes in the size, number, phenotype,
metabolic activity, or functions of cells in response to changes in
their environment.
• Such adaptations may take several distinct forms.
1. Hypertrophy increase in the size of cells, resulting in an
increase in the size of the organ.
2. Hyperplasia an increase in the number of cells in an organ or
tissue, usually resulting in increased mass of the organ or tissue.
3. Atrophy reduced size of an organ or tissue resulting from a
decrease in cell size and number.
4. Metaplasia Reversible change in which one differentiated cell
type is replaced by another cell type.
 Types of Adaptation
• Physiologic adaptations: Physiologic adaptations usually
represent responses of cells to normal stimulation by hormones or
endogenous chemical mediators (e.g., the hormone induced
enlargement of the breast and uterus during pregnancy).

• Pathologic adaptations: Pathologic adaptations are responses to

stress that allow cells to modulate their structure and function and
thus escape injury. Such adaptations can take several distinct
forms.
 Atrophy
• Atrophy is a decrease in the size of an organ or tissue and results
from a decrease in the mass of preexisting cells. Shrinkage in the
size of the cell by the loss of cell substance is known as atrophy.

Types of Atrophy

• Physiologic atrophy

• Pathological atrophy
Atrophy. A, Normal brain of a young adult. B, Atrophy of the brain in an
82-year-old male with atherosclerotic cerebrovascular disease, resulting
in reduced blood supply. Note that loss of brain substance narrows the
gyri and widens the sulci
 Causes
• Decreased workload (atrophy of disuse)
• Nutritional or oxygen deprivation
• Diminished endocrine stimulation
• Aging
• Malnutrition
• Chronic illness  COPD, Cancer, Heart Failure
• Neurological Conditions  spinal injury, multiple sclerosis,
peripheral neuropathy
• Injuries and Trauma
• Medication  corticosteroids
• Hormonal imbalance less thyroid and testosterone causes muscle
weakness and atrophy
 Physiologic atrophy
• Physiologic atrophy is common during normal development.

• For example

- Some embryonic structures, such as the notochord and

thyroglossal duct, undergo atrophy during fetal development.
- The uterus decreases in size shortly after child birth.

- Atrophy of ovaries and uterus after menopause

 Pathologic atrophy
• It refer to loss of muscle or tissue mass due to a disease or
abnormal condition.
• It can occur in various organs or tissue including brain, glands and
muscles.
For example
• Alzheimer disease: neurodegenerative disorder cause brain
atrophy.
• Multiple Sclerosis: disease that damage myelin sheath surrounding
the cell that lead to weakness of muscles and atrophy
• Sarcopenia: loss of muscles mass and strength with age
 Mechanism of atrophy
• In general, there is a balance between protein synthesis and
protein catabolism in normal cell.

• In case of Atrophy, increase in catabolism and decrease in protein

synthesis cause atrophy.

• The hormones such as insulin, thyroid hormones, glucocorticoids,

and growth hormones influence protein turnover.

• A slight increase in protein catabolism for a long period of time

may result in atrophy.
Proteosome pathway
• The degradation of cellular proteins occurs mainly by the ubiquitin-
proteasome pathway.
• Nutrient deficiency may activate ubiquitin ligases which lead to the
degradation of muscle protein and muscle atrophy.
Autophagy
• It is a cellular process that involve the degradation and recycling of
cellular component including organelles & protein through lysosomal
degradation.
• Atrophy also associated with autophagy. The excessive and
dysregulated autophagy lead to degradation of muscle protein like
actin and myosin that lead to muscle wasting.
• Atrophy can be reversible
 Hypertrophy
• Hypertrophy is an increase in the size of an organ or tissue due to
an increase in the size of cells.

• Hypertrophic tissues do not have any new cells, but existing cells
increase in size due to formation of more structural components
within the cell.

• It always be a result of increase demand for work and function.

• Causes:

• hormonal stimulation

• increased workload
 Mechanism
1. Mechanical stress (physiological hypertrophy)
2. Growth factor (pathological hypertrophy)
3. Adrenergic receptors (pathological hypertrophy)
 Mechanical stress Cardiac muscle hypertrophy

Stimulate

Growth factor and adrenergic Hormone

Turn on stimulate Contractile protein  inc. workload demand

Transduction Pathway
Stimulate synthesis of cellular protein
Growth factor and structural protein
Induction of embryonic and
fetal genes like myosin heavy
chain isoform that causes
increase in mechanical stress
which causes increase muscle
growth

Increase protein and myofilament in cell

Increase force generated to meet increase workload

 Types of hypertrophy
There are three types of hypertrophy.

1. Physiological hypertrophy

2. Adaptive hypertrophy

3. Pathological hypertrophy

4. Compensatory hypertrophy
1- Physiological hypertrophy
• It is not the process of any disease. It occurs because of;

- Hormone stimulation  the hypertrophy of pregnant uterus. As at

the end of pregnancy the muscle fibers in the uterus are 10 times
longer and 4 times broader as compared to the non-pregnant
uterus.
 2- Adaptive hypertrophy
• This type of hypertrophy is always associate with the increase demand
for function or workload.

• For example;

• hypertrophy of skeletal muscles due to the increased load that is

exercise another example
• Adaptive hypertrophy is best seen in hollow organs when their
outlet is partially obstructive.
• Hypertrophy of stomach and large intestine wall due to the
intestinal obstruction.
• Hypertrophy of urinary bladder wall in urethral obstruction.
3- Pathological Hypertrophy
• This type of hypertrophy occurs as a result of a disease or abnormal
condition.

• For example, cardiac hypertrophy can occur as a result of chronic

hypertension or aortic stenosis, leading to an enlargement of the
heart muscle.

• Pathological hypertrophy can result in changes in cell structure and

function that can ultimately lead to organ dysfunction and failure if
left untreated.
4- Compensatory hypertrophy
• It is best seen in paired organs.

• Hypertrophy occur to compensate for the loss of tissues.

• For example:

• Hypertrophy of remaining kidney if the other kidney is

removed.

• Compensatory hypertrophy also occur in unpaired organs. When a

part of tissue is removed.

• For example:

• Compensatory hypertrophy in thyroid gland or liver

 Limitations
• Hypertrophy cannot be continued to occur beyond a certain limit
because.
• Limited blood supply to organ.

• Limited oxidative capabilities of mitochondria of cell.

• Protein degradation.
 Clinical significance
• Hypertrophy can produce a disease.

• For example, Left ventricular hypertrophy

• No chance of neoplasia
 Hyperplasia

Hyperplasia is an increase in the number of cells in an organ or

tissue, usually resulting in increased mass of the organ or tissue.
Mechanism: Mechanism of hyperplasia involves the mitotic
division.
Causes:
• Hormonal stimulation
• tissue loss
 Types of Hyperplasia
• Two types of hyperplasia are.

• Physiological hyperplasia

• Pathological hyperplasia

• Physiologic hyperplasia can be divided into

• Hormonal hyperplasia

• compensatory hyperplasia
 a. Hormonal hyperplasia
• Hormonal hyperplasia refers to an abnormal increase in the number
of cells in a tissue or organ due to hormonal imbalances or
overproduction of certain hormones.
• This type of hyperplasia can occur in various tissues and organs
throughout the body, including the breast, uterus, thyroid, and
adrenal glands.
• For example;
- Proliferation of the glandular epithelium of the female breast at
puberty
- Increase in the size of the breasts during pregnancy,
- Increase in thickness of endometrium during menstrual cycle
- liver growth after partial resection
- During pregnancy and growth of the uterus during pregnancy
involves both hypertrophy and hyperplasia.
 b. Compensatory hyperplasia
• Response to deficiency,
• For example
- Hyperplasia following surgical removal of part of liver or of
one kidney;
- Hyperplasia of the bone marrow in anemia
• For example, when part of a liver is resected, mitotic activity in
the remaining cells begins as early as 12 hours later, eventually
restoring the liver to its normal weight. The stimuli for hyperplasia
in this setting are polypeptide growth factors produced by
uninjured hepatocytes as well as nonparenchymal cells in the liver.
After restoration of the liver mass, cell proliferation is ―turned
off by various growth inhibitors
 Pathologic Hyperplasia
• Pathologic hyperplasia is caused by excessive hormonal or growth
factor stimulation.
• For example,
• after a normal menstrual period there is a burst of uterine
epithelial proliferation that is normally tightly regulated by
stimulation through pituitary hormones and ovarian estrogen
and by inhibition through progesterone. However, a disturbed
balance between estrogen and progesterone causes
endometrial hyperplasia, which is a common cause of
abnormal menstrual bleeding
• Benign prostatic hyperplasia
• Pancreatic islet hyperplasia in infants of a diabetic mother.
 Hyperplasia Vs. cancer
• Hyperplasia and cancer are both related to abnormal growth of
cells

Hyperplasia Cancer
Increase in cell number in uncontrolled growth of abnormal
response of stimulus like cells that can invade nearby
inflammation, hormonal changes, tissues and spread to other parts
or tissue damage. of the body that leading to the
The pathologic hyperplasia formation of tumors and the
serves as a favorable destruction of normal tissues.
environment for the eventual
growth of cancer.
 Clinical significance
• Hyperplasia can produce a disease such as Grave`s disease.
• There is increased incidence of neoplasia with hyperplasia.
 Relationship between
hyperplasia and hypertrophy
 Dysplasia
• Premalignant condition

• Increase cell growth

• abnormal cell growth or development in tissues or organs, which

can potentially lead to the development of cancer.

• Dysplasia can occur in various parts of the body, including the

cervix, colon, skin, and respiratory tract.
 Neoplasia
• abnormal and uncontrolled growth of cells in the body.

• Benign

• Malignant

• Benign tumors are usually slow-growing and do not invade

surrounding tissues or spread to other parts of the body,

• Malignant tumors are more aggressive and can invade nearby

tissues and spread to other parts of the body through a process
called metastasis.
 Metaplasia
• It is a reversible change in which one adult cell type (epithelial or
mesenchymal) is replaced by another adult cell type.

• It is a reversible process in which the normal, differentiated cells

of an organ or tissue are replaced by another cell type that is not
normally found in that location.
 Causes
• Chronic irritation

• Chronic inflammation

• Vitamin A Deficiency
 Mechanism
• Metaplasia does not result from a change in the phenotype of an
already differentiated cell type

• It is the result of a

- reprogramming of stem cells that are known to exist in normal

tissues,
- undifferentiated mesenchymal cells present in connective tissue.

• The differentiation of stem cells is brought about by signals

generated by cytokines, growth factors, and extracellular matrix
components in the cells' environment.
 Types
There are following types
1. Epithelial metaplasia
2. Mesenchymal metaplasia/connective tissue metaplasia
3. Glandular metaplasia
4. Osseous metaplasia
 1- Epithelial metaplasia
“It occurs in response to the altered function or environment”.

Examples:

• The normal secretory epithelium is replaced by non-functioning

stratified squamous cells.
• In chronic cigarette smokers (the normal pseudostratified ciliated
columnar epithelium of trachea or bronchi is replaced by the
stratified squamous cells)
• Due to chronic irritation.
• Due to excretory ducts of salivary gland, pancreatic ducts and bile
ducts can be changed due to irritation from stones.
• Vitamin A deficiency

• This process is often reversible

 2- Mesenchymal metaplasia
• Mesenchymal metaplasia, also known as fibrous metaplasia or
connective tissue metaplasia.

• It is a type of metaplasia where one type of tissue that normally

belongs to the mesenchymal tissue category (such as fibrous or
connective tissue) is replaced by another type of tissue that also
belongs to the mesenchymal tissue category.

• Fibrous tissues cartilage and bones are related to each other in structure
and can be changed into one another”

• This process occurs in response to

• chronic irritation
• Inflammation
For example:
• Mesenchymal metaplasia in the urinary tract:
• It occurs in response to chronic irritation from urinary tract
infections or other types of inflammation. The normal
urothelial cells lining the urinary tract can be replaced by
fibrous or connective tissue, which can impair the function of
the urinary tract and lead to conditions such as ureteral
obstruction or urinary incontinence.
• Mesenchymal metaplasia of respiratory tract:
• It occurs in response to chronic irritation from cigarette smoke
or other environmental pollutants. The normal epithelial
tissue lining the respiratory tract can be replaced by fibrous or
connective tissue, which can impair lung function and lead to
conditions such as chronic obstructive pulmonary disease
(COPD).
 3.Glandular metaplasia
• This occurs when one type of epithelial cell is replaced by another
that has the ability to secrete mucus or other substances.

• For example, in the stomach, the columnar epithelium can be

replaced by goblet cells, which secrete mucus.

• Example

• Metaplasia from squamous to columnar type may also occur,

as in Barrett esophagus, in which the esophageal squamous
epithelium is replaced by intestinal-like columnar cells under
the influence of refluxed gastric acid.
 4. Osseous metaplasia
• A non-osseous tissue, such as connective tissue, undergoes
transformation into bone tissue.

• This process is usually a response to chronic inflammation or

injury, and it can occur in various tissues, such as muscle,
cartilage, and connective tissue.
 Clinical significance
• It can produce a disease Barrett's esophagus, Chronic obstructive
pulmonary disease (COPD)

• The chance of neoplasia is increased

 Aplasia
• “Defective development or congenital absence of an organ or tissue”.

• It can occur during embryonic development or later in life due to

injury or disease.

• Causes:

• Hereditary defects in the germplasm that may or may not be sex-

linked.
• Accidental death of a cell at some critical point in the development
of the individual. The earlier this occurs in life, the more likely
there will be serious defect in the mature individual.
• Disease particularly viral during Gestation may invade the fetus
and cause cellular damage.
Microscopic appearance:
• There is a total absence of a tissue or organ involved.
• At times, in the area where the structure should have been, there is
a mass of fat or connective tissue
• Whether Aplasia will be lethal or not, it depends upon what organ
is involved.
• If the heart or brain will fail to develop.
Examples:
• Aplastic anemia
• Renal aplasia
• Pulmonary artery aplasia and etc
 Hypoplasia
• It is an underdevelopment or incomplete development of a tissue,
organ, or body part.

• It is characterized by a decrease in the number or size of cells, that

leads to smaller-than-normal structure or size of the affected tissue
or organ.

• Hypoplasia can occur during fetal development, childhood, or

later in life due to injury or disease.

• the partial lack of growth and maturation of gonadal structures in

Turner syndrome and Klinefelter syndrome.
 Anaplasia
• “Loss of differentiation is called anaplasia”.
Differentiation:
• It is the extent to which the daughter cell resemble to their parent
both structurally and functionally.
Characteristics of well differentiated cells:
• They resemble closely to their normal forebear as both
morphologically and functionally.
• Mitosis in them is less and rate of growth is less
• Benign neoplasia occur in well differentiated cells.
 Characteristics of Anaplasia
• Pleomorphism: variation in size and shape. It applies to the cells and
nuclei.
• Abnormal nuclear morphology: high nuclear cytoplasmic ratio,
hyperchromatism (abundance of DNA), variability of the nuclear
shape and prominence of the nucleoli.
• Mitoses: large number of mitoses reflecting the high proliferative
index. The presence of abnormal mitoses is indicative of
malignancy.
• Loss of polarity: The orientation of the malignant cells is markedly
disturbed.
• Loss of function. This loss of function depend upon the degree of
anaplasia.
• Other changes: presence of giant cells is an example. These may also
be present in inflammatory conditions.
• An example of anaplasia is seen in a high-grade glioma, a type of
brain tumor.

• In this condition, the cells of the tumor lose their normal structure
and function, becoming more primitive and undifferentiated.
 Reference
• Kumar V, Cotran RS, Robbins SL. Robbin’s Basic Pathology. 8th
Ed. W. B. Saunders Publishers; 2007.
• Macfarlane PS, Reid R, Collander R. Pathology Illustrated. 5th
Ed. Churchill Livingstone; 2000.
 Past papers
1 Define hyperplasia and metaplasia with examples 2015

2 Define hypertrophy 2017

3 Define hypertrophy and explain it with example 2019

4 Define atrophy and explain its physiological and 2020

pathological causes

5 Define metaplasia and explain types of metaplasia with 2020

examples

6 Define hypertrophy and explain its mechanism and 2020

types of hypertrophy with example

7 Differentiate b/w hyperplasia and metaplasia 2021