Disorders of cell growth and differentiation

1. Disorders of Cell Growth and
Differentiation
by
OLUSIYAN OLUWATOBI

2. OUTLINE
• Introduction
• Definition of cell growth & cell differentiation
• Disorders of cell growth & cell differention

3. Introduction
•
• The cells of the body continue to grow, divide
and differentiate throughout life. Normally,
growth and differentiation are controlled in
such a way as to maintain the normal
structure of a particular tissue.This is seen in
tissues e.g (skin, intestinal mucosa, blood)
characterized by labile stem cells which
continuously undergo mitosis to replace lost
cells.

4. Introduction (contd)
• The processes of cell growth and
differentiation are the means by which a
single cell develops into a large complex
multicellular organism.Many cells undergo
growth in response to normal (physiological)
or abnormal (pathological) stimuli.

5. ---------What is Cell growth---------
Cell Growth is the process of increase in
size and mass of a cell resulting from the
synthesis of specific cell components.
--------------What is Cell Differentiation-------
Cell Differentiation is the process
whereby a cell develops an overt
/observable specialised morphology or
function which distinguishes it from its
parent cell.

6. DISORDERS OF CELL GROWTH
• Hypertrophy
• Hyperplasia
• Atrophy
• Metaplasia
• Dysplasia
• Anaplasia
• Neoplasia

7. HYPERTROPHY
• Hypertrophy refers to an increase in the size of
cells,that results in an increase in the size of the
affected organ.
• Increased cell size is due to the synthesis and assembly
of additional intracellular structural components.
• The hypertrophied organ has no new cells(due to lack
of cell division) but larger cells.
• Hypertrophy can be:
-Physiologic
-Pathologic

8. HYPERTROPHY(CONTD)
Physiological hypertrophy is caused by:
(A) Increased functional demand which can be found in
the heart &skeletal muscle .The common stimulus for
hypertrophy of muscle is increased work load.E.g is
seen in the bulging muscles of body builders.
(B) Stimulation by hormone & growth factors as seen in
growth of the uterus during pregnancy due to the
estrogen hormone acting on estrogen receptors.
 The pathologic R/L ventricular hypertrophy of the
heart is usually caused by chronic hemodynamic
overload resulting from either hypertension or faulty
valves.

9. MECHANISM OF HYPERTROPHY
• Hypertrophy is the result of increased production of cellular
proteins.
• There are 3 basic steps involved in its molecular pathogenesis.
(1)Integrated action of (a)mechanical sensors(triggered by increased
workload),(b)growth factors e.g IGF-1,FGF,TGF-b and ©vasoactive
agents e.g a-adrenergic agonists,endothelin-1 and angiotensin II.
(2)Activation of signal transduction pathways (PI3K and AKT pathways).
(3)These signaling pathways activate a set of transcription factors such
as GATA4,NFAT and MEF2-which work coordinately to increase the
synthesis the muscle proteins that are responsible for hypertrophy.

10. HYPERPLASIA
• Hyperplasia is defined as an increase in the number of cells in an
organ or tissue in response to a stimulus.
• It can only take place if the tissue contain cells that are capable of
dividing.
• It can be physiologic or pathologic.
 Physiologic hyperplasia occurs in (2) types:
• (a)Hormonal hyperplasia:It increases the functional capacity of a
hormone-sensitive organ e.g, proliferation of the glandular
epithelium of female breasts at puberty and pregnancy, which is
usually accompanied by hypertrophy of glandular epithelial cells.
• (b)Compensatory hyperplasia:This is seen in the regeneration of the
liver after a partial hepatectomy.The remaining cells proliferate so
that organ soon grows back to the original size.
• Another example of physiologic hyperplasia is the production of
RBC’S from the bone marrow in response to its deficiency.

11. HYPERPLASIA(CONTD)
 Pathologic hyperplasia are caused by excessive or
inappropriate actions of hormones or growth factors acting
on cells.
 Examples include:
• -Endometrial hyperplasia due to increased amount of
estrogen.
• -Benign prostatic hyperplasia in responses to hormonal
stimulation by androgens.
• Responses to viral infections like HPV causing warts.
 It can constitute a fertile soil in which cancerous
proliferations can arise when growth control mechanisms
becomes deregulated or ineffective because of genetic
abberations.

12. MECHANISM OF HYPERPLASIA
• Hyperplasia is the result of growth-factor
driven proliferation of mature cells and, in
some cases, by increased output of new cells
from tissue stem cells.

13. ATROPHY
• Atrophy is defined as a reduction in the size of an organ or
tissue due to a decrease in cell size and number-resulting in
the decreased functional ability of the cell.
• It can be physiologic or pathologic.
 (1)Physiologic atrophy
• This is common during normal development.They include:
• Atrophy of notochord & thyroglossal ducts during fetal
development.
• Atrophy of uterus after parturition.
• Atrophy of ductus arteriosus in infants .
• Atrophy of thymus.

14. ATROPHY(CONTD)
(2)Pathologic atrophy.
This may be localized or generalized.
 LOCALIZED:-
*Disuse:When a fractured bone is immobilized in a plaster cast/when
a patient is restricted to complete bed rest,muscle rapidly ensues.
*Denervation:Damage of nerves leads to atrophy of muscles.
*Ischemia: In late adult,the brain undergoes atrophy progressively as
atherosclerosis narrows blood vessels.
*Loss of endocrine stimulation: E.g-The loss of estrogen stimulation
after menopause results in physiologic atrophy of the
endometrium,vaginal epithelium, and breast.
*Pressure:Tissue compression for any length of time can cause atrophy
.An enlarged benign tumor can cause atrophy in surrounding
compressed tissue,probably due to ischemic changes.

15. ATROPHY (CONTD)
GENERALIZED:-
*Inadequate nutrition:Profound protein-calorie
malnutrition(marasmus) is associated with the
utilization of skeletal muscle proteins as a source
of energy after other reserves such as adipose
stores have been depleted.This results in marked
muscle wasting(cachexia).
(3)Senile atrophy as seen in ageing.
It is associated with cell loss,typically seen in the
brain and the heart.

16. Fig 1-5: atrophy A. normal brain of a young adult. B. Atrophy of the brain
in an 82-year-old male with atherosclerotic cerebrovascular disease,
resulting in reduced blood supply. Note that loss of brain substance
narrows the gyri and widens the sulci. The meninges have been striped
from the right half of each specimen to reveal the surface of the brain.

17. MECHANISM OF ATROPHY
• Atrophy results from:
(1)Decreased protein synthesis due to reduced metabolic
activities in the cells.
(2)Increased protein degradation in cells:-This occurs
mainly by the ubiquitin-proteasome pathway.Nutrient
deficiency and disuse activate the ubiquitin ligases
which attach the small ubiquitin molcules to cellular
proteins and target these tagged proteins for
degradation in proteasomes.This pathway is also
thought to be responsible for the accelerated
proteolysis seen in cachexia.

18. The ubiquitin (Ub)-proteasome pathway (UPP) of protein degradation.
Stewart H. Lecker et al. JASN 2006;17:1807-1819

19. MECHANISM(CONTD)
• Atrophy,in many situations,is also accompanied
by increased autophagy(‘’self-eating’’),marked by
the appearance of increased numbers of
autophagic vacuoles.
• Some of the cell debris within the autophagic
vacuoles may resist digestion and persist in the
cytoplasm as membrane-bound residual bodies
called lipofuscin granules-which if present in
sufficient amounts,they impart a brown
discoloration to the tissue (BROWN ATROPHY).

20. METAPLASIA
Metaplasia is an acquired form of altered
differentiation.
Metaplasia is the reversible transformation and
replacement of one type of terminally
differentiated (epithelial or mesenchymal) cell
into another fully differentiated cell type.
 Metaplasia often represents an adaptive
response of a tissue to environmental stress.The
metaplastic tissue is better able to withstand the
adverse environmental changes.

21. EXAMPLES OF METAPLASIA
 The most common metaplasia is columnar to squamous as occurs
in the respiratory tract in response to chronic irritation as seen in an
habitual cigarette smokers.
 A deficiency of vit.A also induces squamous metaplasia in the
respiratory epithelium.
 Metaplasia from squamous to columnar can occur in Barrette
oesophagus under the influence of refluxed gastric acid.
 Stones in the excretory duct of salivary glands,pancreas or bile duct
which are normally lined by secretory columnar epithelium may be
replaced by stratified squamous epithelia.
 Connective tissue metaplasia is the formation of cartilage,bone&
adipose tissues in the tissues that do not originally contain
them...E.g myositis ossificans after intramuscular
haemorrhage(bone fracture).

23. Metaplasia (contd)
• Metaplasia does not itself necessarily progress
to malignancy, although the environmental
changes which initially caused the metaplasia
may also induce dysplasia and, if persistent,
progression to tumour formation.

24. DYSPLASIA
• This is literally known as ‘’disordered growth’’.
• It is an abnormality where a tissue partially loses
the morphological characteristics of mature cells.
• It is mostly encountered in the epithelia.
• It involves 4 major changes:
 (1)Anisocytosis(cells of unequal sizes)
(2)Poikilocytosis(abnormally shaped cells)
(3)Hyperchromatism(Excessive pigmentation)
(4)Presence of mitotic figures(unusual no of
continually dividing cells)

25. Dysplasia (contd)
• These changes result in the loss of uniformity and
architectural orientation of the cells.
• Dysplasia=Earliest form of a precancerous lesion.
• It is also an indication of premature neoplastic
progression.
• Dysplasia may occur in tissue which has
metaplasia (i.e., dysplasia developing in
metaplastic squamous epithelium from the
bronchus of smokers). Dysplasia may also
develop without coexisting metaplasia, for
example in squamous epithelium of the uterine
cervix, glandular epithelium of the stomach, or
the liver.

26. ANAPLASIA
• ANAPLASIA (LACK OF DIFFERENTIATION)IS A
MORE ADVANCED STAGE THAN DYSPLASIA.
• IT IS THE HALLMARK OF MALIGNANT
NEOPLASMS.
• ‘’Detailed explanation of the above underlined
terms will be made in the next presentation’’.

27. Thank You