DEBRE BIRHAN UNIVERSITY

SCHOOL OF MEDICINE
PATHOLOGY DEPARTMENT
CELLULAR ADAPTATION
FOR 2nd Yr PUBLIC HEALTH STUDENTS

BY: Dr. ABEBAW T.

Presentation out lines
• Introduction
•
• Types of cellular adaptations

• Clinical importance

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Cellular Adaptation
I. Cellular adaptation by growth

II. Cellular adaptation by maturation or differentiation

III. Adaptation abnormalities of both maturation and differentiation

IV. Intracellular Accumulations

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• Cells respond to pathologic or physiologic stimuli by undergoing
physiologic/functional or morphologic adaptation

• Cellular behavior not changed but modified

• Proposed mechanisms include:

1. direct stimulation by growth factors

2. up regulation or down regulation of receptors
3. directly by induction of protein synthesis by target cells

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Three basic groups of cell adaptation
1. Adaptation by growth
• Hypertrophy
• Hyperplasia
• Atrophy

2. Adaptation by maturation and differentiation

• Metaplasia

3. Intracellular accumulation

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1. Hyperplasia
• it is an increase in number of cells leading to increase in volume of an organ or
tissue.

• Occurs in cells capable of mitosis

• Can occur along with hypertrophy

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Cont…
• Hyperplasia can be

a. Physiological hyperplasia.
• Hormonal hyperplasia.

E.g. enlargement of glandular epithelium of breast, monthly endometrial proliferation

• Compensatory hyperplasia.

E.g. Partial hepatectomy followed by regeneration

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 b. Pathological hyperplasia
• The effect of excessive hormonal or growth factor stimulation of a target cell
E.g. Endometrial hyperplasia, prostatic hyperplasia

• The process is controlled

• E.g. removal of the stimulating factor results in regression of hyperplasia

• i.e. target cells are responsive to normal regulatory control mechanisms

• Cancer cells, in contrast, have defective control mechanisms

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• N.B.
Pathologic hyperplasia, however, constitutes a fertile soil in which cancerous
proliferation may eventually arise

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Hypertrophy
This is increase in the size of cells leading to increased size of an organ or tissue
(no new cells, just larger cells)

• Stimuli include increased functional demand (workload), or hormones

• due to the synthesis of more structural components (not due to cellular swelling)

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 Cont…
• Physiologic hypertrophy- E.g. the muscles of body builders, the pregnant uterus,
lactating breast, etc

• Pathologic hypertrophy-

• E.g. Cardiac muscle responding to chronic hemodynamic stress like hypertension

or faulty valves

• Pathologic cardiac hypertrophy eventually reaches a limit beyond which

enlargement of muscle mass is no longer able to compensate for the increased
burden, and cardiac failure results

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 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 (left) compared with C,
large plump cells in gravid uterus (right).

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Atrophy
A shrinkage of cellular size as a result of loss of intracellular components

• Although atrophic cells may have diminished function, they are not dead

• However, atrophy may progress to cell injury or death

A. Physiological atrophy- E.g. early development (branchial clefts, thyroglossal

duct, umblical vessels, notochord), reduction in uterine size following
parturition

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 B. Pathological atrophy
-can be local or generalized
Types include:
• Decreased workload (atrophy of disuse)
• Diminished blood supply
• Loss of innervation (denervation atrophy)
• Inadequate nutrition/ Starvation
• Loss of endocrine stimulation
• Aging (senile atrophy)
• Pressure atrophy-compression effect

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Con..

• They represent a retreat by the cell to a smaller size at which survival is still
possible

• A new equilibrium is achieved between cell size and diminished blood supply,
nutrition, or trophic stimulation

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 Mechanisms of atrophy
• Cellular atrophy results from a combination of decreased protein synthesis
and increased protein degradation
• Protein synthesis decreases because of reduced metabolic activity
• Mechanisms include:
• Lysosomal hydrolases (autophagy)
• The ubiquitin-proteasome pathway
• The degradation of cellular proteins occurs mainly by the ubiquitin-
proteasome pathway
• Nutrient deficiency and disuse may activate ubiquitin ligases, which attach
multiple copies of the small peptide ubiquitin to cellular
proteins and target them for degradation in proteasomes
• This pathway is also thought to be responsible for the accelerated proteolysis
seen in a variety of catabolic conditions, including the cachexia associated with
cancer
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 Con..
• atrophy also is associated with autophagy, with resulting increases in the number of
autophagic vacuoles

• autophagy is the process in which the starved cell eats its own organelles in an attempt to
survive

• lipofuscin granules are residual bodies

• certain cell debris within autophagic vacuoles resist digestion

• Brown atrophy- When lipofuscin is in sufficient amount to impart brown discoloration of

tissues

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 Metaplasia
Is a reversible change in which one adult cell type (epithelial or
mesenchymal) is replaced by another adult cell type

• An adaptive substitution of cells to a stressful environment by cells better able

to withstand the adverse condition

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 Mechanisms of metaplasia
• Metaplasia does not result from a change in the phenotype of a differentiated
cell type

• Metaplasia is thought to arise through reprogramming of stem cells (reserve

cells) present in all epithelia or undifferentiated mesenchymal cells present in
connective tissue.

• differentiation of stem cells to a particular lineage is brought about by signals

generated by cytokines, growth factors, and extracellular matrix components in
the cell's environment.

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Epithelial metaplasia
1. Commonest form is from columnar to squamous epithelium

E.g. i. Respiratory epithelium

ii. Gall bladder, pancreatic or salivary duct
iii. Uterine cervix

2. Metaplasia of transitional epithelium to squamous epithelium

E.g. Renal pelvis or urinary bladder

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 Metaplasia of normal columnar (left) to squamous epithelium (right) in a bronchus,
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shown (A) schematically and (B) histologically
3. Glandular metaplasia- where squamous epithelium is replaced by columnar
epithelium
E.g. GERD causing Barrett esophagus

4. Metaplasia from glandular to other types of glandular epithelium (Intestinal

metaplasia)
E.g. Chronic atrophic gastritis where pylorus and antrum epithelium shows an
increase in goblet cells and Paneth cells in response to Helicobacter pylori

 Connective tissue metaplasia- formation of bone, cartilage or adipose tissue in

tissues where it usually doesn’t exist
E.g. Myositis ossificans

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 Clinical importance
• Metaplasia is a two-edged sword!

• Loss of mucus secretion in trachea or bronchi predisposes to infection

• Persistence of stimuli can predispose to cancer

• Thus in most instances, metaplasia is an undesirable change

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SUMMARY CELLULAR ADAPTATIONS TO STRESS

Hypertrophy: increased cell and organ size, often in response to increased

workload; induced by growth factors produced in response to mechanical stress
or other stimuli; occurs in tissues incapable of cell division
Hyperplasia: increased cell numbers in response to hormones and other
growth factors; occurs in tissues whose cells are able to divide or contain
abundant tissue stem cells

• Atrophy: decreased cell and organ size, as a result of decreased nutrient

supply or disuse; associated with decreased synthesis of cellular building blocks
and increased breakdown of cellular organelles and autophagy

• Metaplasia: change in phenotype of differentiated cells, often in response to

chronic irritation, that makes cells better able to withstand the stress; usually
induced by altered differentiation pathway of tissue stem cells; may result in
reduced functions or increased propensity for malignant transformation

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 Intracellular Accumulations

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• Under some circumstances, cells may accumulate abnormal amounts of various
substances, which may be harmless or may cause varying degrees of injury

• The substance may be located in the cytoplasm, within organelles (typically

lysosomes), or in the nucleus

• The main pathways of abnormal intracellular accumulations are inadequate removal

and degradation or excessive production of an endogenous substance, or deposition
of an abnormal exogenous material

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 PATHOLOGIC CALCIFICATION
• Pathologic calcification, a common process in a wide variety of disease
states, is the result of an abnormal deposition of calcium salts, together with
smaller amounts of iron, magnesium, and other minerals

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Con..
• It can occur in two ways:-
• Dystrophic calcification: calcium metabolism is normal but it deposits in injured
or dead tissue, such as areas of necrosis of any type

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Dystrophic calcification
• It is virtually ubiquitous in the arterial lesions of advanced atherosclerosis

• Although dystrophic calcification may be an incidental finding indicating

insignificant past cell injury, it also may be a cause of organ dysfunction.

• calcification can develop in aging or damaged heart valves, resulting in severely

compromised valve motion

• Dystrophic calcification of the aortic valves is an important cause of aortic

stenosis in elderly persons

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 Con..
• Dystrophic calcification is initiated by the extracellular deposition of crystalline
calcium phosphate in membrane-bound vesicles, which may be derived from
injured cells, or the intracellular deposition of calciumin the mitochondria of
dying cells

• It is thought that the extracellular calcium is concentrated in vesicles by its

affinity for membrane phospholipids, whereas phosphates accumulate as a
result of the action of membrane bound phosphatases

• The crystals are then propagated, forming larger deposits

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Metastatic calcification
associated with hypercalcemia and can occur in normal tissues

The major causes of hypercalcemia are (1) increased secretion of parathyroid

hormone, due to either primary parathyroid tumors or production of parathyroid
hormone–related protein by other malignant tumors

 (2) destruction of bone due to the effects of accelerated turnover (e.g., Paget
disease), immobilization, or tumors (increased bone catabolism associated with
multiple myeloma, leukemia, or diffuse skeletal metastases)

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Con..
(3) vitamin D–related disorders including vitamin D intoxication and sarcoidosis
(in which macrophages activate a vitamin D precursor)

(4) renal failure, in which phosphate retention leads to secondary

hyperparathyroidism

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 MORPHOLOGY
• Dystrophic calcification is common in areas of caseous necrosis in
tuberculosis

• Tuberculous lymph node is essentially converted to radiopaque stone

• Metastatic calcification can occur widely throughout the body but principally
affects the interstitial tissues of the vasculature, kidneys, lungs, and gastric mucosa
• Although they generally do not cause clinical dysfunction,

• Extensive calcifications in the lungs may be evident on radiographs and may

produce respiratory deficits, and massive deposits in the kidney (nephrocalcinosis)
can lead to renal damage (CKD)

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 THANK YOU

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