DR. SANKET DER
A S S I S T A N T PR O F E S S O R
PA T HOL O G Y D E PA R T M E N T
GM C H
CELLULAR ADAPTATIONS
Cellular responses to cell injury
CELLULAR ADAPTATIONS
 When there is increased functional demand, the cell may
adapt to the changes which are expressed morphologically,
which then revert back to normal after the stress is removed.
 Reversible changes in the size , shape, phenotype, metabolic
activity or function of cells in response to changes in
environment.
Two types :
 Physiologic adaptation
 Pathologic adaptation
Common form of cellular adaptive
response
Atrophy
Hypertrophy
Hyperplasia
Metaplasia
Dysplasia
Atrophy
 Reduction of the number and size of parenchymal
cells of an organ or its parts which was once normal is
called atrophy.
Two types
 Physiological
 pathological
Physiologic atrophy
 Ageing in some tissues, which could be due to loss of
endocrine stimulation or arteriosclerosis.
For example:
 Atrophy of lymphoid tissue with age.
 Atrophy of thymus in adult life.
 Atrophy of gonads after menopause.
 Atrophy of brain with ageing.
Pathological atrophy
 Starvation atrophy - In starvation, there is first depletion
of carbohydrate and fat stores followed by protein catabolism.
e.g.
i) cancer
ii)severely ill patients.
 Ischaemic atrophy - Gradual diminution of blood supply
due to atherosclerosis may result in shrinkage of the affected organ.
e.g.
i) Small atrophic kidney in atherosclerosis of renal artery.
ii) Atrophy of the brain in cerebral atherosclerosis.
 Disuse atrophy - Prolonged diminished functional
activity is associated with disuse atrophy of the organ.
e.g.
i) Wasting of muscles of limb immobilised in cast.
ii) Atrophy of the pancreas in obstruction of pancreatic duct.
 Neuropathic atrophy - Interruption in nerve
supply leads to wasting of muscles.
e.g.
i) Poliomyelitis
ii) Motor neuron disease
 Endocrine atrophy - Loss of endocrine
regulatory mechanism results in reduced metabolic
activity of tissues and hence atrophy .
e.g.
i) Hypopituitarism may lead to atrophy of thyroid,
adrenal and gonads.
ii) Hypothyroidism may cause atrophy of the skin and
its adnexal structures.
 Pressure atrophy - Prolonged pressure from benign tumours
or cyst or aneurysm may cause compression and atrophy of the tissues.
e.g.
i) Erosion of the spine by tumour in nerve root.
ii) Erosion of the sternum by aneurysm of arch of aorta.
 Idiopathic atrophy - There are some examples of atrophy
where no obvious cause is present.
e.g.
i) Myopathies.
ii) Testicular atrophy.
Morphological features
 The organ is small, often shrunken. The cells
become smaller in size but are not dead cells.
 Shrinkage in cell size is due to reduction in cell
organelles, chiefly mitochondria,myofilaments
and endoplasmic reticulum.
Hypertrophy
 Hypertrophy is an increase in the size of
parenchymal cells resulting in enlargement of the
organ or tissue, without any change in the number of
cells.
Two types :
 Physiological
 Pathological
Physiologic hypertrophy
 Enlarged size of the
uterus in pregnancy
Normal Hypertrophy
Microscopic
Pathological hypertrophy
Hypertrophy of
Cardiac muscle –
 CVS diseases.
 A few conditions producing
left ventricular hypertrophy
are as under:
i) Systemic hypertension
ii) Aortic valve disease
iii) Mitral insufficiency
Normal Hypertrophy
Microscopic
 Hypertrophy of smooth muscle
i) Cardiac achalasia (in oesophagus)
ii) Pyloric stenosis (in stomach)
iii) Intestinal strictures
iv) Muscular arteries in hypertension
 Hypertrophy of
skeletal muscle
 Hypertrophied muscles in
athletes and manual
labourers.
 Compensatory hypertrophy may occur in
an organ when the contralateral organ is removed.
e.g.
Following nephrectomy on one side in a young
patient, there is compensatory hypertrophy as well
as hyperplasia of the nephrons of the other kidney.
Morphological features
 Affected organ is enlarged and heavy.
Example
 Hypertrophied heart of a patient with systemic hypertension
may weigh 700-800 g as compared to average normal adult
weight of 350 g.
 There is enlargement of muscle fibres as well as of nuclei.
At Ultra-structural level
 Increased synthesis of DNA and RNA,
 Increased protein synthesis
 Increased number of organelles such as mitochondria,
endoplasmic reticulum and myofibrils.
Hyperplasia
 Hyperplasia is an increase in the number
of parenchymal cells resulting in enlargement
of the organ or tissue.
 Quite often, both hyperplasia and hypertrophy
occur together.
Two types
 Physiological
 Pathological
Physiologic hyperplasia
 Two types : Hormonal and Compensatory
1. Hormonal hyperplasia - Hyperplasia occurring
under the influence of hormonal stimulation.
e.g.
1) Hyperplasia of female breast
at puberty, during pregnancy
and lactation.
2) Hyperplasia of pregnant uterus.
3) Prostatic hyperplasia in old age.
Microscopic
2. Compensatory hyperplasia –
Hyperplasia occurring following removal of part of an organ
or in the contralateral organ in paired organ.
e.g.
1) Regeneration of the liver following partial hepatectomy.
2) Regeneration of epidermis after skin abrasion.
3) Following nephrectomy on one side, there is hyperplasia
of nephrons of the other kidney.
 Hyperplasia are due to excessive stimulation of
hormones or growth factors.
1) Endometrial hyperplasia following estrogen excess.
2) In wound healing, there is formation of granulation tissue
due to proliferation of fibroblasts and endothelial cells.
3) Intraductal epithelial hyperplasia in the breast in
fibrocystic breast disease.
Pathologic hyperplasia
Normal Hyperplasia
Microscopic
Morphological features
 There is enlargement of the affected organ or
tissue and increase in the number of cells.
 This is due to increased rate of DNA synthesis
and hence increased mitoses of the cells.
Metaplasia
 Reversible change of one type of epithelial or
mesenchymal adult cells to another type of adult
epithelial or mesenchymal cells, usually in response to
abnormal stimuli, and often reverts back to normal on
removal of stimulus.
 However, if the stimulus persists for a long time, epithelial
metaplasia may progress to dysplasia and further into cancer.
TWO TYPES
 Epithelial
 Mesenchymal.
Epithelial metaplasia
 More common type.
 Metaplastic change may be patchy or diffuse and
usually results in replacement by stronger but less well
specialised epithelium.
Depending upon the type of epithelium transformed,
TWO TYPES of metaplasia.
 Squamous metaplasia
 Columnar metaplasia
Epithelial metaplasia
1. Squamous metaplasia.
 Variable types of specialised epithelium are capable of
undergoing squamous metaplastic change due to chronic
irritation that may be mechanical, chemical or infective in
origin.
1) In bronchus (normally lined by pseudostratified columnar
ciliated epithelium) in chronic smokers.
2) In uterine endocervix (normally lined by simple columnar
epithelium) in prolapse of the uterus and in old age.
Squamous metaplasia of the uterine cervix
Squamous metaplasia of the uterine cervix
3) In gallbladder (normally lined by simple columnar
epithelium) in chronic cholecystitis with cholelithiasis.
4) In prostate (ducts normally lined by simple columnar
epithelium) in chronic prostatitis and oestrogen therapy.
5) In renal pelvis and urinary bladder (normally lined
by transitional epithelium) in chronic infection and stones.
2. Columnar metaplasia
1) Columnar metaplasia in Barrett’s oesophagus,
in which there is change of normal squamous
epithelium to columnar epithelium.
2) Conversion of pseudostratified ciliated columnar
epithelium in chronic bronchitis and
bronchiectasis to columnar type
Columnar metaplasia oesophagus (Barrett’s oesophagus).
Mesenchymal metaplasia
 There is transformation of one adult type of
mesenchymal tissue to another.
TWO TYPES
 Osseous metaplasia
 Cartilaginous metaplasia
1. Osseous metaplasia - formation of bone in fibrous
tissue, cartilage and myxoid tissue.
1) In arterial wall in old age (Mönckeberg’s sclerosis).
3) In cartilage of larynx and bronchi in elderly people.
4) In scar of chronic inflammation of prolonged duration.
5) In the fibrous stroma of tumour e.g. in leiomyoma.
2. Cartilaginous metaplasia
 In healing of fractures, cartilaginous metaplasia may
occur where there is undue mobility.
DYSPLASIA
 Dysplasia means ‘disordered cellular
development’,
 Often preceded or accompanied with
metaplasia and hyperplasia; it is therefore also
referred to as atypical hyperplasia.
 Dysplasia occurs most often in epithelial
cells.
 Epithelial dysplasia is characterized by cellular
proliferation and cytologic changes as under:
1. Increased number of layers of epithelial cells
2. Disorderly arrangement of cells
3. Loss of basal polarity
4. Cellular and nuclear pleomorphism
5. Increased nucleocytoplasmic ratio
6. Nuclear hyperchromatism
7. Increased mitotic activity.
• Dysplastic change occur due to chronic
irritation or prolonged inflammation
• On removal of stimulus changes may disappear.
• In some cases dysplasia may progress into
carcinoma in situ or invasive cancer.
• Example : dysplastic change in uterine cervix.
Uterine cervical dysplasia
- Increased number of layers of squamous epithelium
- Marked cytologic atypia including mitoses
Features METAPLASIA DYSPLASIA
1. Definition Change of one type of
epithelial or mesenchymal
cell to another type of adult
epithelial ormesenchymal cell
Disordered cellular
development, may be
accompanied with
hyperplasia or metaplasia
2. Types Epithelial (squamous,
columnar) and mesenchymal
(osseous,cartilaginous)
Epithelial only
3. Tissues affected Most commonly affects
bronchial mucosa, uterine
endocervix; others
mesenchymal tissues
(cartilage,arteries)
Uterine cervix,
bronchial mucosa
4. Cellular changes Mature cellular
development
Disordered cellular
development
(pleomorphism, nuclear
hyperchromasia, mitosis,
loss of polarity
5. Natural history Reversible on withdrawal of May regress on removal
 Atrophy - physiological,pathological
 Hypertrophy – physiology,pathological
 Hyperplasia – physiological (hormonal n
compansatory), pathological
 Metapasia – epithelial (squamous,columnar),
mesenchymal (osseous, cartilagenous)
 Dysplasia

Cellular adaptation General Pathology. .

  • 1.
    DR. SANKET DER AS S I S T A N T PR O F E S S O R PA T HOL O G Y D E PA R T M E N T GM C H CELLULAR ADAPTATIONS
  • 2.
  • 3.
    CELLULAR ADAPTATIONS  Whenthere is increased functional demand, the cell may adapt to the changes which are expressed morphologically, which then revert back to normal after the stress is removed.  Reversible changes in the size , shape, phenotype, metabolic activity or function of cells in response to changes in environment. Two types :  Physiologic adaptation  Pathologic adaptation
  • 4.
    Common form ofcellular adaptive response Atrophy Hypertrophy Hyperplasia Metaplasia Dysplasia
  • 6.
    Atrophy  Reduction ofthe number and size of parenchymal cells of an organ or its parts which was once normal is called atrophy. Two types  Physiological  pathological
  • 7.
    Physiologic atrophy  Ageingin some tissues, which could be due to loss of endocrine stimulation or arteriosclerosis. For example:  Atrophy of lymphoid tissue with age.  Atrophy of thymus in adult life.  Atrophy of gonads after menopause.  Atrophy of brain with ageing.
  • 9.
    Pathological atrophy  Starvationatrophy - In starvation, there is first depletion of carbohydrate and fat stores followed by protein catabolism. e.g. i) cancer ii)severely ill patients.  Ischaemic atrophy - Gradual diminution of blood supply due to atherosclerosis may result in shrinkage of the affected organ. e.g. i) Small atrophic kidney in atherosclerosis of renal artery. ii) Atrophy of the brain in cerebral atherosclerosis.
  • 10.
     Disuse atrophy- Prolonged diminished functional activity is associated with disuse atrophy of the organ. e.g. i) Wasting of muscles of limb immobilised in cast. ii) Atrophy of the pancreas in obstruction of pancreatic duct.  Neuropathic atrophy - Interruption in nerve supply leads to wasting of muscles. e.g. i) Poliomyelitis ii) Motor neuron disease
  • 11.
     Endocrine atrophy- Loss of endocrine regulatory mechanism results in reduced metabolic activity of tissues and hence atrophy . e.g. i) Hypopituitarism may lead to atrophy of thyroid, adrenal and gonads. ii) Hypothyroidism may cause atrophy of the skin and its adnexal structures.
  • 12.
     Pressure atrophy- Prolonged pressure from benign tumours or cyst or aneurysm may cause compression and atrophy of the tissues. e.g. i) Erosion of the spine by tumour in nerve root. ii) Erosion of the sternum by aneurysm of arch of aorta.  Idiopathic atrophy - There are some examples of atrophy where no obvious cause is present. e.g. i) Myopathies. ii) Testicular atrophy.
  • 13.
    Morphological features  Theorgan is small, often shrunken. The cells become smaller in size but are not dead cells.  Shrinkage in cell size is due to reduction in cell organelles, chiefly mitochondria,myofilaments and endoplasmic reticulum.
  • 14.
    Hypertrophy  Hypertrophy isan increase in the size of parenchymal cells resulting in enlargement of the organ or tissue, without any change in the number of cells. Two types :  Physiological  Pathological
  • 15.
    Physiologic hypertrophy  Enlargedsize of the uterus in pregnancy
  • 16.
  • 17.
    Pathological hypertrophy Hypertrophy of Cardiacmuscle –  CVS diseases.  A few conditions producing left ventricular hypertrophy are as under: i) Systemic hypertension ii) Aortic valve disease iii) Mitral insufficiency
  • 18.
  • 19.
     Hypertrophy ofsmooth muscle i) Cardiac achalasia (in oesophagus) ii) Pyloric stenosis (in stomach) iii) Intestinal strictures iv) Muscular arteries in hypertension
  • 20.
     Hypertrophy of skeletalmuscle  Hypertrophied muscles in athletes and manual labourers.
  • 21.
     Compensatory hypertrophymay occur in an organ when the contralateral organ is removed. e.g. Following nephrectomy on one side in a young patient, there is compensatory hypertrophy as well as hyperplasia of the nephrons of the other kidney.
  • 22.
    Morphological features  Affectedorgan is enlarged and heavy. Example  Hypertrophied heart of a patient with systemic hypertension may weigh 700-800 g as compared to average normal adult weight of 350 g.  There is enlargement of muscle fibres as well as of nuclei. At Ultra-structural level  Increased synthesis of DNA and RNA,  Increased protein synthesis  Increased number of organelles such as mitochondria, endoplasmic reticulum and myofibrils.
  • 23.
    Hyperplasia  Hyperplasia isan increase in the number of parenchymal cells resulting in enlargement of the organ or tissue.  Quite often, both hyperplasia and hypertrophy occur together. Two types  Physiological  Pathological
  • 24.
    Physiologic hyperplasia  Twotypes : Hormonal and Compensatory 1. Hormonal hyperplasia - Hyperplasia occurring under the influence of hormonal stimulation. e.g. 1) Hyperplasia of female breast at puberty, during pregnancy and lactation. 2) Hyperplasia of pregnant uterus. 3) Prostatic hyperplasia in old age.
  • 26.
  • 27.
    2. Compensatory hyperplasia– Hyperplasia occurring following removal of part of an organ or in the contralateral organ in paired organ. e.g. 1) Regeneration of the liver following partial hepatectomy. 2) Regeneration of epidermis after skin abrasion. 3) Following nephrectomy on one side, there is hyperplasia of nephrons of the other kidney.
  • 28.
     Hyperplasia aredue to excessive stimulation of hormones or growth factors. 1) Endometrial hyperplasia following estrogen excess. 2) In wound healing, there is formation of granulation tissue due to proliferation of fibroblasts and endothelial cells. 3) Intraductal epithelial hyperplasia in the breast in fibrocystic breast disease. Pathologic hyperplasia
  • 29.
  • 30.
    Morphological features  Thereis enlargement of the affected organ or tissue and increase in the number of cells.  This is due to increased rate of DNA synthesis and hence increased mitoses of the cells.
  • 31.
    Metaplasia  Reversible changeof one type of epithelial or mesenchymal adult cells to another type of adult epithelial or mesenchymal cells, usually in response to abnormal stimuli, and often reverts back to normal on removal of stimulus.  However, if the stimulus persists for a long time, epithelial metaplasia may progress to dysplasia and further into cancer. TWO TYPES  Epithelial  Mesenchymal.
  • 32.
    Epithelial metaplasia  Morecommon type.  Metaplastic change may be patchy or diffuse and usually results in replacement by stronger but less well specialised epithelium. Depending upon the type of epithelium transformed, TWO TYPES of metaplasia.  Squamous metaplasia  Columnar metaplasia
  • 33.
    Epithelial metaplasia 1. Squamousmetaplasia.  Variable types of specialised epithelium are capable of undergoing squamous metaplastic change due to chronic irritation that may be mechanical, chemical or infective in origin. 1) In bronchus (normally lined by pseudostratified columnar ciliated epithelium) in chronic smokers. 2) In uterine endocervix (normally lined by simple columnar epithelium) in prolapse of the uterus and in old age.
  • 34.
    Squamous metaplasia ofthe uterine cervix
  • 35.
    Squamous metaplasia ofthe uterine cervix
  • 36.
    3) In gallbladder(normally lined by simple columnar epithelium) in chronic cholecystitis with cholelithiasis. 4) In prostate (ducts normally lined by simple columnar epithelium) in chronic prostatitis and oestrogen therapy. 5) In renal pelvis and urinary bladder (normally lined by transitional epithelium) in chronic infection and stones.
  • 37.
    2. Columnar metaplasia 1)Columnar metaplasia in Barrett’s oesophagus, in which there is change of normal squamous epithelium to columnar epithelium. 2) Conversion of pseudostratified ciliated columnar epithelium in chronic bronchitis and bronchiectasis to columnar type
  • 38.
    Columnar metaplasia oesophagus(Barrett’s oesophagus).
  • 39.
    Mesenchymal metaplasia  Thereis transformation of one adult type of mesenchymal tissue to another. TWO TYPES  Osseous metaplasia  Cartilaginous metaplasia
  • 40.
    1. Osseous metaplasia- formation of bone in fibrous tissue, cartilage and myxoid tissue. 1) In arterial wall in old age (Mönckeberg’s sclerosis). 3) In cartilage of larynx and bronchi in elderly people. 4) In scar of chronic inflammation of prolonged duration. 5) In the fibrous stroma of tumour e.g. in leiomyoma. 2. Cartilaginous metaplasia  In healing of fractures, cartilaginous metaplasia may occur where there is undue mobility.
  • 41.
    DYSPLASIA  Dysplasia means‘disordered cellular development’,  Often preceded or accompanied with metaplasia and hyperplasia; it is therefore also referred to as atypical hyperplasia.  Dysplasia occurs most often in epithelial cells.
  • 42.
     Epithelial dysplasiais characterized by cellular proliferation and cytologic changes as under: 1. Increased number of layers of epithelial cells 2. Disorderly arrangement of cells 3. Loss of basal polarity 4. Cellular and nuclear pleomorphism 5. Increased nucleocytoplasmic ratio 6. Nuclear hyperchromatism 7. Increased mitotic activity.
  • 43.
    • Dysplastic changeoccur due to chronic irritation or prolonged inflammation • On removal of stimulus changes may disappear. • In some cases dysplasia may progress into carcinoma in situ or invasive cancer. • Example : dysplastic change in uterine cervix.
  • 44.
    Uterine cervical dysplasia -Increased number of layers of squamous epithelium - Marked cytologic atypia including mitoses
  • 45.
    Features METAPLASIA DYSPLASIA 1.Definition Change of one type of epithelial or mesenchymal cell to another type of adult epithelial ormesenchymal cell Disordered cellular development, may be accompanied with hyperplasia or metaplasia 2. Types Epithelial (squamous, columnar) and mesenchymal (osseous,cartilaginous) Epithelial only 3. Tissues affected Most commonly affects bronchial mucosa, uterine endocervix; others mesenchymal tissues (cartilage,arteries) Uterine cervix, bronchial mucosa 4. Cellular changes Mature cellular development Disordered cellular development (pleomorphism, nuclear hyperchromasia, mitosis, loss of polarity 5. Natural history Reversible on withdrawal of May regress on removal
  • 46.
     Atrophy -physiological,pathological  Hypertrophy – physiology,pathological  Hyperplasia – physiological (hormonal n compansatory), pathological  Metapasia – epithelial (squamous,columnar), mesenchymal (osseous, cartilagenous)  Dysplasia

Editor's Notes