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

with life.

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

tissue

Hypertrophy

Increase in size of cells and thus increase in size of organ or tissue

Occur in tissue whose cells can not divide-

Striated 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 (non-neoplastic)

accompanied by loss of regular differentiation.

The change is considered as preneoplastic.

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