Cell Adaptations

Dr.Kiran Singh Rajput MD(Pathology)

Entities under Cell Adaptations

• Hypertrophy
• Hyperplasia
• Atrophy
• Aplasia & hypoplasia
• Metaplasia
• Dysplasia
 Learning Objectives
1. Define adaptation.
2. Define physiologic hyperplasia; discuss examples.
3. Define pathologic hyperplasia; explain the given examples; recognize morphologic features.
4. Define physiologic hypertrophy; discuss the given examples.
5. Define pathologic hypertrophy; explain the given examples; recognize morphological
features.
6. Define physiologic atrophy; discuss the given examples.
7. Define pathologic atrophy; explain the given examples; recognize morphological features.
8. Define and differentiate marasmus and cachexia.
9. Define metaplasia; describe the given examples, recognize morphological features.
10. Define dysplasia; explain principles of identification.
 Cellular response to stresses and injurious stimuli

Hypertrophy
Hyperplasia
Atrophy
Metaplasia
 Cell Adaptation
In response to the prolonged environmental stress, the cell undergoes the
adaptation to better cope with the situation. Cell adaptation is potentially
reversible change if the environmental stress is removed.
It can be:
• Hypertrophy
• Hyperplasia
• Atrophy
• Metaplasia
• Dysplasia (not a true adaptation)
Cell Adaptation
 Hypertrophy
• It means INCREASED SIZE of cells in a tissue, generally resulting in increased size
of the organ.
• It results from the increased synthesis and assembly of intracellular structural
components.
• Hypertrophy can be physiological or pathological, which can result from increased
functional demand, or by stimulation by hormones or cytokines which lead to
increased expression of genes and increased protein synthesis.
• Hypertrophy and hyperplasia often occur together.
Morphological characteristics
Biochemical mechanisms of myocardial hypertrophy

G-coupled receptor pathway (PI3-kinase/AKT pathway)

 Physiological Hypertrophy

• Bulging muscles of bodybuilders is result from enlargement of individual

muscle fibers in response to increased demand.

• Due to aerobic exercise, there is cardiac hypertrophy due to increased

hemodynamic load.
• Uterus during pregnancy: Hormonal changes cause hypertrophy (both
hyperplasia & hypertrophy occur).
• Removal of an organ: Removal of one kidney causes hypertrophy of the
remaining kidney.
 Myometrial hypertrophy

Physiologic hypertrophy of the uterus during pregnancy.

A. Gross appearance of a normal uterus (right) and a gravid uterus (removed for postpartum
bleeding) (left).
B. Small spindle-shaped uterine smooth muscle cells from a normal uterus, compared with C,
large plump cells from the gravid uterus, at the same magnification.
 Pathological Hypertrophy
• Occurs due to some pathological processes, for example:
• Left ventricular hypertrophy, occuring in response to hypertension, or
aortic stenosis.
• Cell enlargement, occuring in cytomegalovirus (CMV) infection.
• Cytomegaly occurs because the virus increases the uptake of iron into
the cytosol, which increases the growth of the cell.
• Bladder muscle hypertrophy due to bladder calculus, or due to BPH
(benign prostate hyperplasia).
• Diverticular disease (outpouching of the intestines).
Left ventricular hypertrophy

Left
ventricular
hypertrophy
 Case study
A 67 year old man presents with severe left lower quadrant
pain (LLQ).
He has a history of long-standing constipation and occasional
dull ache and cramping in the LLQ (left lower quadrant).
On examination, there is marked tenderness in the LLQ.
It resulted in pressure induced diverticulosis (outpouching) of
intestinal smooth muscle (hypertrophy).
Diverticular disease (Diverticulosis)
(Outpouching)
Diverticular disease (Diverticulosis)

smooth muscle hypertrophy

 HYPERPLASIA
Definition: Increased size of an organ due to INCREASED NUMBER of cells.
It can be physiologic, or pathologic.
Cells, unable to undergo hyperplasia: neuron, cardiac, skeletal muscle.
Triggers & Mechanism:
• Hormones/Growth factors (VEGF, EGF, HGF, etc.) drive the proliferation of mature cells, or stem
cells.
• Stimulation by autoantibodies (Grave’s disease).
• Chronic irritation (itchy thickened skin).
• Compensatory response to increased demands.
• Infections: warts due to HPV infection.
Hyperplasia can be physiologic, and pathologic.
 Physiologic Hyperplasia
Results due to the action of hormones or growth factors.
Examples include:
• Increased functional capacity of hormone-sensitive organs: Proliferation of the
glandular epithelium of female breast at puberty, and during pregnancy.
• Compensatory increase after damage or resection; e.g. in individuals who donate one
lobe of the liver for transplantation, the remaining cells proliferate and the liver grows
back to its original size.
• Rapid hyperplasia of bone marrow in response to an acute blood loss.
 Pathologic Hyperplasia
Caused by excessive or inappropriate actions of hormones or growth factors, acting on
the target cells.
1. Increased hormone stimulation; example:
• Endometrial gland hyperplasia, caused by an increased estrogen.
• Benign prostatic hyperplasia (BPH), caused by an increased sensitivity to dihydro-
testosterone (DHT).

2. Chronic irritation; example:

• Constant scratching of itchy skin, which can produce thickening
• (hyperplasia) of the Epidermis.
 Pathologic Hyperplasia
3. Viral infections: example:
• Skin infection by the human papillomavirus (HPV) produces
• can result in epidermal hyperplasia, or warts.

4. Chemical imbalance: examples:

• Hypocalcemia, which stimulates parathyroid gland hyperplasia
(secondary hyperparathyroidism) to increase serum calcium levels.
• Iodine deficiency, leads to thyroid gland hyperplasia.

5. Stimulating antibodies: example:

• Hyperthyroidism in Grave’s disease is due to thyroid-stimulating antibodies (IgG), directed against
thyroid hormone receptors, causing stimulation of the receptors, leading to increased number of
the gland cells, and increased synthesis of thyroid hormones.
 Pathologic hyperplasia
Benign Prostatic hyperplasia
 Pathologic Hyperplasia
Antibody stimulation
Grave’s disease (hyperthyroidism)

Graves disease
 Pathologic Hyperplasia
Adrenal gland hyperplasia

Adrenal gland hyperplasia,

resulting from increased ACTH-
producing tumor of
Hypophysis of pituitary gland

Normal
 Case study
• A 45 years old women visited gynecologist due to irregular vaginal bleeding.
She is married and has three children. History is suggestive of excessive
amount of blood whenever she has the bleeding.

• No other abnormalities were observed. Vaginal examination showed blood in

the vaginal canal without any mass. What may be the possible causes for her
irregular vaginal bleeding?
 Endometrial Hyperplasia

The endometrial cavity showing hyperplastic

endometrium.

Endometrial hyperplasia usually results with

conditions of prolonged estrogen-excess and
can lead to metrorrhagia (uterine bleeding at
irregular intervals), menorrhagia (excessive
bleeding with menstrual periods), or meno-
metrorrhagia.
 Endometrial Hyperplasia
Normal

Normal endometrial glands Hyperplasic endometrial glands

 Case study
A 33 years old male visited for regular check up.

Family history suggests that his uncle died of colon cancer.

After lab investigations, he was found to have a positive Stool
guaiac test.

What is the next step in the management?

 Colonoscopy showed multiple polyps

Some polyps are malignant, some are

premalignant, and
Polyp is essentially descriptive term for something some are completely benign.
that grows into the lumen of the epithelial lining, it
does not tell anything about pathology of the
disease until microscopy is performed.
Normal Colonic hyperplastic polyp results from
excessive proliferation of epithelial cells.
 Combined hyperplasia and hypertrophy
• Usually, hyperplasia is combined with hypertrophy.
• In pregnancy, myometrial smooth muscle cells are increased not only in number but
also in size.
• Prostatic enlargement, known as BPH (benign prostatic hyperplasia), is predominantly
caused by hyperplasia of prostatic glands and stromal smooth muscle cells.
• These cells are also enlarged, hence hypertrophy also occurs.
• This in turn almost always leads to thickening of an obstructed urinary bladder due to
both hypertrophy and hyperplasia of smooth muscle cells.
• Goiter (enlarged thyroid gland) in iodine deficiency.
 • ATROPHY
• Atrophy is a decrease in the size of an organ or tissue and results from a decrease in
the mass of preexisting cells.

• Atrophy results from decreased protein synthesis due to reduced metabolic activity
and increased protein degradation in cells.
• b)
• Most often, causal factors are disuse (immobilization), nutritional or oxygen
deprivation, diminished endocrine stimulation, aging, and denervation (lack of nerve
stimulation in peripheral muscles caused by injury to motor nerves).
• -
• Characteristic features often include shrunken cells with autophagic granules
(intracytoplasmic vacuoles).
• In some instances, atrophy is thought to be mediated in part by the ubiquitin–
proteasome pathway of protein degradation.
• In this pathway, ubiquitin-linked proteins are degraded within the proteasome,
a large cytoplasmic protein complex.

• It can be:

• 1. Physiologic Atrophy;

• 2. Pathologic Atrophy
1. Physiologic Atrophy
Involution involving apoptosis of cells:
• Post partum involution of the uterus.
• Postmenopausal (loss of estrogen) atrophy of glandular
elements of the breast, vagina, and endometrial tissue.
• Thyroglossal duct during fetal development.
• Ductus arteriosus during neonatal development.
• Thymus in adults.
 Endometrial atrophy (postmenopausal)

Atrophic Endometrium. Low power. The endometrial glands are few and
Normal Endometrium
are lined by a low cuboidal epithelium. The stroma is abundant and fibrotic.
2. pathologic atrophy
Decreased workload, E.g. Muscle atrophy when a fractured bone is immobilized in a plaster cast,
or when a patient is restricted to complete bed rest.
Loss of innervation, E.g. Skeletal muscle atrophy following a denervation (due to trauma),
or following the loss of lower motor neurons in amyotrophic lateral sclerosis.
Diminished blood supply, E.g. Cerebral atrophy.
Inadequate nutrition, E.g. Marasmus, or Anorexia Nervosa.
Loss of endocrine stimulation, E.g. hypopituitarism, causing atrophy of target organs, such
as thyroid and adrenal cortex.
Pressure, E.g. Hydrocephalus (brain parenchyma atrophy); atrophy of the renal cortex and medulla in
hydronephrosis; thick pancreatic duct secretions in cystic fibrosis occlude the duct lumens of exocrine pancreas and
cause atrophy.
Atrophy of the brain- Atrophy of the brain-
Hydrocephalus Atherosclerotic cerebrovascular disease

Loss of brain substance narrows the gyri and widens

the sulci.
Skeletal Muscular Atrophy

Atrophy of skeletal muscles after

denervation of small nerve fibers.
 Poliomyelitis Hand muscle atrophy

Normal muscle Atrophic muscle fibers (arrows)

 • There are pathologic processes other than atrophy that can reduce the organ
size:
• Agenesis:
• Refers to absence of an organ due to absence of primordial tissue during the
embryonic life.
• E.g. Renal agenesis
• Aplasia:
• The primordium is present but there is no further development of the organ.
• E.g. Aplasia of adrenal cortex.
• Hypoplasia:
• Refers to incomplete or partial development of an organ or tissue.
• E.g. Streak ovary in down syndrome.
 MARASMUS AND CACHEXIA
MARASMUS: Marasmus is a severe malnutrition (general calorie
deficiency), characterized by underweight, with the loss of
muscle mass and subcutaneous fat.
It mostly occurs in children.
CHACHEXIA: Cachexia is a syndrome characterized by
progressive loss of muscle mass and body fat, and a loss of
appetite due to underlying disease. Cachexia is caused due to
the cytokines (TNF- α, IL-1, IL-6, IFN-γ) which are released from
tumor, or inflammatory cells which cause reduced gene
transcription and increased degradation of myosin and lipolysis.
 METAPLASIA
Definition - Change of one mature cell type to another, usually epithelial cells. This
is often a reversible process.
Mechanisms: Reserve cell or Stem cell reprogramming.
Triggers:
Environmental changes, e.g. constant exposure to irritants (exogenous or
endogenous).
E.g. Chronic reflux acid disease, causing Barrette metaplasia (columnar
metaplasia);
Cigarette smoking and Vitamin A deficiency in respiratory epithelium to cause
squamous (keratinized) metaplasia.
Barrett esophagus, showing an extensive area of glandular (intestinal) metaplasia with
numerous goblet cells. A small section of squamous epithelium remains on the right.
 Metaplasia (Epithelial examples)
1. Columnar metaplasia: Chronic reflux acid disease, causing Barrette esophagus with
columnar metaplasia (squamous replaced by columnar).
2. Squamous metaplasia
a. Replacement of columnar epithelium by squamous epithelium at the
squamocolumnar junction of the uterine cervix.
b. Replacement pancreatic ducts columnar cells by squamous cells.
c. Bronchial epithelium to squamous epithelium due to long-term tobacco use.
Squamous metaplasia of bronchus
 Metaplasia (Mesenchymal examples)
1. Osseous metaplasia
Osseous or osteoid metaplasia is the formation of new bone at the site of tissue injury. It
has been frequently observed in scars, chronic inflammatory & degenerative lesions,
sclerotic arteries and muscles (myositis ossificans circumscripta).
Cartilaginous metaplasia may also occur.

2. Myeloid metaplasia
It is an extramedullary hematopoiesis is the proliferation of hematopoietic tissue at the sites
other than the bone marrow, such as the liver and spleen.
 Metaplasia (Mesenchymal examples)
• Formation of cartilage, bone or adipose tissue (mesenchymal tissues) in tissues that
normally do not contain these elements.
• Example: bone formation in the muscle – “myositis ossificans” – Osteoid Metaplasia
Myositis ossificans circumscripta
 Common tissues susceptible to metaplasia and
the stimuli that can cause the change

Tissue Normal Metaplasia Stimulus

Airways Pseudostratified Squamous epithelium Cigarette smoke

columnar epithelium

Urinary bladder Transitional epithelium Squamous epithelium Schistosoma

haematobium

Esophagus Squamous epithelium Columnar epithelium Gastro-esophageal reflux

(Barrett’s)

Endo-Cervix Columnar epithelium Squamous epithelium pH reduction during

first puberty
 Dysplasia
 NOT truly an adaptation. It is a disorderly growth.

 Principally occurs in epithelium, and is characterized by atypical growth and

proliferation of cells.

The cells show:

• changes in size and shape
• Increased N/C ratio
• loss of organization
• Increased mitotic activity

Normal Dysplastic epithelium

 Usually seen in hyperplastic or metaplastic epithelium.
Normal Dysplastic epithelium

52
 Causes of dysplasia
Hyperplasia :
• Endometrial hyperplasia caused by estrogen excess
Metaplasia :
• Squamous metaplasia of bronchus in smokers
Infection :
• HPV type 16 infection, causing cervical dysplasia
Ultraviolet light :
• Solar damage to skin, causing squamous dysplasia
 Dysplasia
Dysplasia arises from metaplastic or hyperplastic process.
It may progress to cancer if irritating stimulus is not removed!
Dysplasia is a reversible change if the irritant is removed
Not a cancer, but may progress to cancer, hence is preneoplastic lesion.
dysplasia may not progress to neoplasia.

Examples:
Squamous dysplasia of the cervix, associated with Squamous carcinoma
Squamous dysplasia of bronchus in smokers associated with Squamous
carcinoma
Glandular dysplasia, associated with adenocarcinoma
Barrett’s esophagus, associated with adenocarcinoma
Thank you!