Abnormal growth in tissue

Lecture outcomes
To describe adaptive changes of the cell
to
pathological stimuli
To understand abnormalities of cell
differentiation
To define the terms aplasia, agenesis,
dysplasia, hypoplasia, atrophy,
hypertrophy,
hyperplasia, metaplasia
To understand each of the above with
appropriate examples

Introduction
Inflammatory, Degenerative &
Neoplastic
Growth Increase in size, structure &
function. Synthesis of tissue
components.
Differentiation: functional and structural
maturity of cells.
Proliferation- increase in cell
population.
Tumour Swelling / new growth / mass

Cell cycle & controls

Cyclins, CDK
Growth factors
Growth Inhibitors
Cancer suppressor
gene p53
Oncogenes

Histologic picture of Mitosis:

Factors affecting growth:

Genetic parents, Pygmies.
Endocrine DM, Iodine, GH.
Nutrition - deficiencies/excess.
Stress psycho-social, diseases.
Neoplasia DNA mutation loss of
control
over cell division.

Disorders of Growth
Decreased growth
Hypoplasia, Aplasia, Atrophy
Increased growth
Non Neoplastic Normal DNA
Due to a need.. Controlled.
Neoplastic Abnormal DNA
not needed, auto, uncontrolled.

Non-Neoplastic Proliferation
*Controlled, Reversible, Normal DNA
Hypertrophy *Increase in Size of
cells.
Hyperplasia *Increase in Number of
cells.
Metaplasia *Change from one type to
other
Dysplasia *Disordered, irregular, no
maturation.

Aplasia/ Agenesis
Failure of development of tissue or organ,
which is a developmental abnormality that
presumably develops early in intra uterine
life.
Aplastic organs are either totally absent
or
represented by small mass of fibrous or
fatty
tissue containing a few rudimentary cells.
Paired organs adrenals, kidneys, lungs
Aplasia of aorta or pituitary incompatible

Hypoplasia
Failure of organ to attain full size
Less severe abnormality than aplasia.
Rudimentary organs, smaller than
normal.
Lack full complement of cells, so
function may be reduced.
Usually affects same paired & unpaired
organs as aplasia.

Aplasia

Hypoplasia

Atrophy
Reduction in size of tissue due to shrinkage in
size of cell substance or number of cells or
both.
Physiological uterus, thyroglossal duct.
Pathological atrophy
Disuse atrophy decreased workload
muscle
Denervation atrophy
Ischaemia Brain, atherosclerosis.
Nutrition Protein energy malnutrition,
cachexia.
Endocrine breast, endometrium.
Senile brain, heart
Pressure

Biochemical changes
Balance between protein synthesis and
degradation.
Increased protein degradation
proteolytic
enzymes.
Stimulated by Cytokines TNF
Autophagic vacuoles membrane bound
vacuoles within cells containing
mitochondria,
ER.

Pathology of Atrophy
Microscopically - Cells may be fewer
(numerical) or smaller than normal (quantitative
atrophy).
Grossly - The organ or part is smaller than
normal.
Paired organs - one organ is reduced in size &
wt
compared with its counterpart.
Fatty atrophy: Missing cells replaced by
adipose
tissue as in physiologic atrophy of the thymus
Fibrous atrophy: replaced by fibrous
connective

Hypertrophy
Increase in size of cells and thus
increase in size of organ or tissue
Occur in tissue whose cells can not
divideStriated muscle
Increase in size of many tissues and
organs hypertrophy and hyperplasia

Hypertrophy
No new cells, just larger cells.
Not due to cell swelling, but synthesis
of more structural compounds
Nuclei have higher DNA content, cell
arrests without undergoing mitosis.

Mechanism of hypertrophy
The nature of the signal to the cell is
poorly
understood.
There is an increase in total cellular
proteins,
including myofibril in muscle cells and
organelles such as mitochondria, ER and
myofilaments.
The anabolic processes exceed catabolic
processes.

Types of hypertrophy
PHYSIOLOGICAL
Skeletal muscles ---- weight lifters,
athletes
Hormonal stimulation Uterus
smooth muscles during pregnancy
oestrogen
Breast lactation prolactin
PATHOLOGICAL
Myocardial hypertrophy stenotic
(narrowing) valvular diseases or lung
diseases

Cardiac hypertrophy

Hyperplasia
It is the increase in size of an organ
due to
increase in number of its constituent
cells
Occur in those organs/ tissues whose
cells can divide
Hyperplasia after the removal of the
stimuli, does not progress.

Types of hyperplasia
PHYSIOLOGICAL - Increased level of a normal stimulus
(hormonal)
In regeneration liver regeneration after injury.
As a compensatory response, e.g., missing organ in
paired
organ, partial resection
PATHOLOGICAL due to excessive response or
excessive
stimulation.
thyroid gland (goitre) iodine def.
bronchial epithelium chronic irritation
Hormonal Stimulation uterine, high oestrogen
Excessive growth factor stimulation warts HPV

Goitre Iodine Deficiency

Non neoplastic
Normal DNA
Reversible

Metaplasia
Mature differentiated (highly
specialized) cell type is replaced by
another differentiated cell (less
specialized ) type.
Response to better withstand the
adverse
environment
Prolonged irritation, chronic infection.

Epithelial metaplasia
Endocervix, gall bladder, urinary
bladder, renal pelvis, respiratory tract
(smoking), stomach.
Original columnar or transitional
mucosa
changes to squamous.
Stomach change from acid/ enzyme
secreting epithelium to colonic type
intestinal mataplasia.

Connective tissue metaplasia

Most commonly associated with repair
process
Fibroblasts mesenchymal ability to
change into other connective tissue
cells,
-undergo metaplasia to bone,
cartilage

Dysplasia
Alteration in size, shape and
orientation of
epithelial cells.
Is abnormal development of tissue or
disorderly growth, or malformation of
tissue.
A proliferative response (nonneoplastic)
accompanied by loss of regular
differentiation.
The change is considered as

Salient features of dysplasia

Commonly associated with chronic
inflammation or irritation.
Epithelium of cervix, skin, oesophagus,
endometrium.
Cells increase in number with thickening
of
epithelium, mitosis increased.
Reversible if irritation removed, however,
changes may persist and progress to
malignancy.

Pathology of dysplasia
Microscopically
Cell atypia and disorderliness
Loss of uniformity of the individual cells
and loss of architectural orientation
Cellular atypia is characterized by
pleomorphism and hyperchromasia
Mitotic figures are seen in abundant
cells
Grossly
No much can be appreciated grossly

Ageing
Cellular ageing is the result of a
progressive
decline in the proliferative capacity and
life
span of cells, with accumulation of
cellular
and molecular damage.

Factors affecting Ageing

Genetic 60%
Age gene on Chromosome 1
Environmental factors (40%)
Trauma
Diseases Atherosclerosis, diabetes
Diet malnutrition, obesity
Psychological & Social health stress

Cellular mechanisms of
ageing
Ageing genes
DNA mutation
Free radicle injury
Mitochondrial DNA damage
Loss of DNA repair mech.

Ageing Morphologic
changes

Easy bruising fragile capillaries

Glycosylation of lens proteins Cataract
Brown atrophy heart, atrophy uterus
Skin elastosis, hair loss, bruising
Joints - osteoarthritis
Immunity - Immunosuppression
CVS Blood vessel hardening
atherosclerosis, MI, stroke
Neoplasms
CNS cerebral degeneration

Questions?
baranikarikalan@imu.edu.my