Cell Growth Patterns/Disorders

of Growth
Prof.Abdul Jabbar N. Al-Shammari
The cell cycle
 The eukaryotic cell cycle
consists of distinct phases
 The most dramatic events are
nuclear division (mitosis) and
cytoplasmic division
(cytokinesis)
 This is the M phase
 The rest of the cell cycle is
called interphase which is,
deceptively, uneventful
 During interphase the cell
replicates its DNA, transcribes
genes, synthesises proteins
and grows in mass
Phases of the cell cycle
S phase – DNA
replicates
M phase – nucleus
divides (mitosis) and
cytoplasm divides
(cytokinesis)
G1 phase – gap between
M and S phase
G2 phase – between S
and M phase
Cellular adaptations of growth and
differentiation
Cells must respond to a variety of stimuli that may be
hormonal, paracrine or through direct cell contact
These stimuli may arise under physiological or
pathological conditions
The way that cells adapt in terms of growth and
differentiation depends in part on their ability to
divide
Growth and differentiation responses
Change in size of cells
Atrophy: Reduction in the size of
cells
Hypertrophy: Increase in the size
of cells
Change in number of cells
Involution: Decrease in the
number of cells
Hyperplasia: Increase in the
number of cells
Change in differentiation of cells

Metaplasia:
Stable change to another cell type
Physiological adaptations
They represent response of cells to normal
stimulation by hormones or endogenous chemical
substances
e.g.
a. enlargement of the breast and induction of
lactation by pregnancy.
b. replacement of labile tissues, e.g. skin, bone
marrow
c. cyclic as endometrium.
Pathological adaptations

adaptations occurring as a result of certain

stimuli which are not lethal,
i.e. a state intermediate between normal
unstressed cells and injured overstressed
ones.
Atrophy
Definition
Reduction of the size of an organ
after reaching its normal adult size.
As a result of decrease in both
the number and size of the cells.
Often associated with fibrosis.
 May be physiological or pathological
Physiological atrophy
Involution:
A form of physiologic atrophy.
Return to normal size after hyperplasia and
hypertrophy, if the causative stimuli are
removed and equilibrium returns back..
Eg
uterus after labour.
atrophy of the ovary after menopause
 senile atrophy of geriatrics.
 b- Pressure atrophy:
due to long continued pressure on a tissue
leading to decrease in its blood supply with
atrophy of its cells
e.g. amyloidosis of the liver in which the
extracellular deposition of amyloid substance
leads to pressure atrophy of hepatocytes.
c-Neuropathic atrophy:
e.g. when a motor nerve supplying a muscle is
affected as in poliomyelitis
d- Decreased work load:
e.g. immobilized limb
e- Starvation: leading to generalized atrophy.
The atrophic cells in all cases, are still surviving
cells, but with diminished function.
Atrophy
When the mass of functioning cells in a tissue becomes
reduced, the tissue is said to have undergone atrophy.

1. There are two mechanisms of reduction:

Decrease in the size and volume of individual cells,
associated with reduction in cellular metabolism
and reduced synthesis of structural proteins.
Physical reduction in the size of
established cells is achieved
through an increase in the
catabolism of structural proteins by
autophagy, channelling redundant
structural elements into the
lysosomal system.
,Death of established cells in an organ or tissue .2
causing a reduction in the number of functioning
cells. There is activation of specific genes, which
.act to bring about cellular dissolution
One of the
morphological manifestations of this type of cell
.death is termed apoptosis
Involution is a form of
physiological organ atrophy involving apoptosis of
.cells
Increased Growth: Hypertrophy and
Hyperplasia
Hyperplasia and hypertrophy are common tissue
responses
• May be physiological (e.g. breast enlargement
in pregnancy) or pathological (e.g. prostatic
enlargement in elderly men)
• Hypertrophy: increase in cell size without cell division
• Hyperplasia: increase in cell number by mitosis
Hyperplasia
Definition:
It is an increase in the size of an organ or tissue due to
increase in the number of constituent parenchymal
cells. It may be physiological or pathological.
Physiological hyperplasia

hormonal as in the female breast

during puberty and pregnancy
compensatory as in hyperplasia of
liver hepatocytes after partial
hepatectomy due to increase in its
functional demands.
Pathological hyperplasia

Increased level of circulating hormones produce

hyperplasia in the target organs

e.g. a- hyperplasia of the endometrium

due to hyperestrinism

b-senile prostatic hyperplasia

due to increase in the level of androgen and
estrogen.
However, hyperplasia due to
certain stimuli stops with removal
of these stimuli and may serve a
useful function.
Hypertrophy
Definition

It is an increase in the size of an organ or tissue due to

enlargement of individual cells without increase in the
number of cells.

It usually occurs in organs in which proliferation and

mitosis are restricted
e.g. skeletal muscle and heart muscles.

It may be physiological or pathological.

1- Physiological hypertrophy

e.g. pregnant uterus, and muscles of

athletes.

2- Pathological hypertrophy

(adaptive hypertrophy)

e.g. a- hypertrophy of the stomach in pyloric

stenosis
b- cardiac muscle hypertrophy in chronically
hypertensive patients.
Increased functional demand on a tissue can be met
by increase in cell number (Hyperplasia), as well as by
increase in cell size (Hypertrophy).

Certain organs or tissues may adapt to a disease

process by increasing functional cell mass.
: mechanisms of increase
1. Hyperplasia is an increase in the number of cells in a
tissue caused by increased cell division.
As this type of change can only occur in tissues that have
the capacity for cell division,
hyperplasia is not an adaptive response seen in
skeletal muscle,
cardiac muscle or nerve cells,
which are non-dividing cell populations.
Hormonal influences are important in this growth
response
.
2. Hypertrophy is an increase in the size of existing
cells, accompanied by increase in their functional
capacity. Cell enlargement is brought about by
increased synthesis of structural components,
associated with accelerated activity of cellular
metabolism and rises in levels of RNA and organelles
required for protein synthesis.
Hypertrophy is
particularly seen as a response to
increased demand in tissues
composed of cells which are unable
to divide (skeletal and cardiac
muscle).
Metaplasia
Definition
It is a reversible change in which an adult cell
type (epithelial or mesenchymal) is replaced
by another adult cell type of the same tissue.
Metaplasia
• Cells can adapt to change in environment by
differentiation to a new, mature, stable type of
cell which is better equipped to withstand an
environmental stress.
• Metaplasia is an acquired form of altered
differentiation
Epithelial squamous metaplasia

e.g. a- uterine endocervical glandular

epithelium due to chronic irritation
b-transitional epithelium of
urinary bladder, ureter or renal pelvis
due to chronic irritation by
bilharziasis or stones
c-columnar epithelium of gall bladder
due to chronic irritation by stones or
inflammation

d-pseudostratified ciliated
columnar respiratory epithelium due to
chronic irritation by habitual cigarette
smoking or in vitamin A deficiency.
The adaptive metaplastic epithelium is better able to survive, but

important protective mechanisms (such as mucus secretion and ciliary

clearance of particulate matter in the respiratory epithelium) are lost.

If the influences that induce metaplastic transformation of the

epithelium are persistent, they may lead to cancer transformation in the

metaplastic epithelium, e.g. squamous metaplasia of transitional

epithelium of the urinary bladder by bilharziasis will lead to squamous

cell carcinoma.
Mesenchymal cell metaplasia:

Myxomatous change of fibrous tissue.

Transformation of fibroblasts to
osteoblasts or chondroblasts to
produce bone or cartilage in soft
tissues in foci of injury.
It may represent an adaptive
substitution of cells more sensitive to
stress by other cell
types better able to withstand the
adverse environment.

Metaplasia is thought to arise by

genetic 'deprogramming" of epithelial
stem cell or of undifferentiated
mesenchymal cells in connective
tissue.
• Transformation of one mature differentiated cell type
into another.
• Reversible response to altered cellular environment.
• Affects epithelial or mesenchymal cells.
• May undergo further indirect transformation to
neoplasia via dysplasia (e.g. squamous cell carcinoma
associated with squamous metaplasia in bronchi).
Examples of Metaplasia
Metaplastic Tissue Stimulus Original Tissue
Squamous epithelium Cigarette smoke Ciliated columnar
epithelial of bronchial
tree
Squamous epithelium Trauma of bladder Transitional epithelium
calculus of bladder
Squamous epithelium Trauma of calculus Columnar epithelium in
gland ducts
Bone (osseous) tissue Chronic trauma Fibro-collagenous tissue
Columnar epithelium Gastric acid Oesophageal squamous
epithelium
Squamous epithelium Vitamin A deficiency Columnar glandular
epithelium
Hypoplasia
It is the decrease in size of an organ due to
incomplete development in embryonic or fetal life
e.g. kidney and uterus.
Agenesis

Complete absence of an organ or

a part of an organ e.g. solitary
kidney, in such case the other
kidney is absent.
Dysplasia
A term used to describe disorderly but non-
neoplastic proliferation.

It is a loss in the uniformity of individual cells as

well as in their architectural orientation
Dysplasia
Dysplasia is characterized by increased cell growth
(e.g. more mitoses visible than normal), presence of
atypical morphology (e.g. abnormally large nuclei),
and altered differentiation (e.g. cellular immaturity)
• May be caused by chronic physical or chemical injury
• May be reversible only in early stages
• Dysplastic lesions are often pre-neoplastic
When dysplastic changes are mild they are
often reversible by removal of the inciting
cause (e.g. chronic irritation).

On the other hand, when dysplastic changes

are marked and involve the entire thickness of
the epithelium, the lesion in this case is
considered as pre-invasive neoplasm and is
referred to as "carcinoma in situ".
Dysplastic changes reveal pleomorphism,

hyperchromatism, abundant mitoses, and loss of

normal orientation. Dysplastic changes are mostly

seen in epithelial cells especially in the cervix uteri.

Neoplasia
Neoplasia is characterized by abnormal, uncoordinated
and excessive cell growth
• Persists after initiating stimulus has been withdrawn
• Associated with genetic alterations
• Neoplastic cells influence behaviour of normal cells by
the production of hormones and growth factors
Summary
 Adapted
Cell

Cellular adaptations to stress

1. Hyperplasia (more cells)
2. Hypertrophy (bigger cells)
3. Atrophy (smaller cells)
4. Metaplasia (different type of cells)
Hypertrophy of uterus
Photomicrograph of the trachea from a smoker. Note that the columnar
.ciliated epithelium has been replaced by squamous epithelium
Decreased Growth: Atrophy
• Atrophy: decrease in size of an organ or cell
• Organ atrophy may be due to reduction in cell size or
number or both
• May be mediated by apoptosis
• Atrophy may be physiological (e.g. postmenopausal
atrophy of uterus)
• Pathological atrophy may be due to decreased
function (e.g. an immobilised limb), loss of enervation,
reduced blood or oxygen supply, nutritional
impairment or hormonal insufficiency
Metaplasia versus Dysplasia
Dysplasia is a pathological term used to refer to an irregularity that .1
hinders cell maturation within a particular tissue whereas Metaplasia is
the process of the reversible substitution of a distinct kind of cell with
.another mature cell of the similar distinct kind

.Dysplasia is cancerous whereas Metaplasia is non-cancerous .2

Metaplasia can be stopped by removing the abnormal stimulus, but .3

.Dysplasia is a non-reversible process
End of chapter