Biomedical Sciences Year 3

Cellular Pathology and Blood Science

Module
Cell Adaptations
Prof. J. Louise Jones
Barts Cancer Institute
Barts and the London School of Medicine
 Recommended Text

• Lecture Notes!!!

• Robbins and Cotran Pathologic Basis of Disease.

Kumar Abbas Fausto. 7th Edition Elsevier Saunders
Response to injury:
 Aims of Lecture
• Causes of cell Adaptation
• Definitions:
– Hypertrophy
– Hyperplasia
– Atrophy
– Hypoplasia
– Metaplasia
– Dysplasia
• Examples of each
• Different cell types
 Cell Adaptation

• Many cell adaptations involve changes in cell

growth, in cell size or in cell differentiation

• Adaptations are a physiological event but

also occur in response to pathological/
abnormal stimuli
 Adaptive Mechanisms

• Hyperplasia
• Hypertrophy
• Atrophy
• (Hypoplasia)
• Metaplasia
 Hyperplasia

• Increase in the number of cells in a

tissue resulting in an increase in the
size of the organ
 Hyperplasia

• Physiological
– hormonal:
• breast at puberty/pregnancy
• uterine smooth muscle during pregnancy
– compensatory
• following partial hepatectomy
• chronic hypoxia (increase in RBC)
 Hyperplasia

• Pathological
– hormonal
• unopposed effect of oestrogens on endometrium
Although pathological hyperplasia is
reversible, it may be a risk factor for the
development of malignancy
– wound healing
• keloid formation
NORMAL BREAST PREGNANT BREAST
 Hypertrophy

• Increase in the size of cells in response

to increased demand.
• Not accompanied by cell division
(though hypertrophy and hyperplasia
may co-exist)
 Hypertrophy

• Physiological
– hormonal
• uterus in pregnancy
– compensatory
• increase in size of skeletal muscle in body builders
 Hypertrophy

• Pathological
– increase in size of cardiac muscle in
response to obstruction (valvular disease)
or increased resistance (hypertension).
Hypertrophy is accompanied by changes in gene
expression e.g. contractile proteins, re-expression of
fetal genes: aMHC expressed in normal adults, bMHC in
fetal heart - this has lower level of ATPase activity and
contracts more slowly. Hypertrophy is associated with
switch from a - b isoform.
Hypertrophy
Hypertrophy
HYPERTROPHY OF BLADDER MUSCLE
DUE TO PROSTATE DISEASE
 Atrophy

• Pathological
– decreased workload
• disuse atrophy e.g. skeletal muscle wasting
following fracture and immobilisation
– loss of innervation
• denervation atrophy
– diminished blood supply
• brain atrophies with age due to progressive
narrowing of blood vessels
Disuse Atrophy
 Hypoplasia

• Failure to achieve normal size of organ

due to developmental abnormality e.g
hypoplastic left heart
 Metaplasia

• Metaplasia is a reversible event in which one

adult, fully differentiated type of tissue is
replaced by another fully differentiated type
of tissue, which is better suited to the
environmental conditions.

• In most situations metaplasia is regarded as

an adaptive change
 Metaplasia

• Physiological
– change in endocervical epithelium from
glandular to squamous - squamous
metaplasia
Cervix: transformation zone
TRANSITIONAL ZONE OF CERVIX
 Metaplasia
• Squamous metaplasia in respiratory tract due to
chronic irritation

• squamous metaplasia of salivary gland ducts,

bile ducts,due to obstruction

• squamous metaplasia of urinary bladder due to

chronic infection

• squamous to columnar metaplasia in oesophagus

- Barretts oesophagus - due to acid reflux
 Metaplasia
• Although regarded as an adaptive response,
metaplastic tissue is ‘unstable’, and areas of
metaplasia are frequent sites for development of
malignancy

– transitional zone of cervix

– Barretts oesophagus
– lung carcinoma on background of squamous
metaplasia
Barretts Oesophagus
 Dysplasia and Anaplasia
• Dysplasia means disordered
differentiation

• Lack of differentiation is termed

anaplasia
 Dysplasia and Anaplasia
• Characterised by several features:
– Pleomorphism
• Variation in size and shape
– Abnormal nuclear morphology
• Nuclei contain abundant DNA and are dark
staining – hyperchromatic
– Mitoses
• Reflecting increased proliferation
– Loss of polarity
• Orientation of cells is disturbed
Dysplastic Squamous
Epithelium
 What determines cell response?

• Major factor is cell type.

• Three ‘populations’ identified:

– labile cells
– stable cells
– permanent cells
 Cell Types

• Labile cells: continually dividing cells

– squamous epithelium of skin, mouth, other

mucus membranes
– glandular epithelium of intestine,
endometrium
– haemopoietic cells
 Cell Types

• Stable cells:normal rate of

growth/turnover is very low, but can
proliferate in response to stimulus

– liver
– renal tubular epithelium
– endocrine glands
 Cell Types

• Permanent cells: cells unable to divide

– neurones
– cardiac muscle
– skeletal muscle
 Susceptibility to cell injury

Depends on

• Cell type
– Active membrane exchange - renal tubular cells
– Neurones have very little ability to use anaerobic
respiration

• Metabolic state of the cell

– Depleted reserves of glycogen - liver damaged by
alcohol also easily damaged by drugs.
 Susceptibility to hypoxia

High: neurones 3-5mins

Medium: myocardium, hepatocytes, renal tubules -

30mins -2hrs

Low : fibroblasts, skeletal muscle

many
hrs
 Summary
• Concept of cell adaptation
• Definition and examples of:
– Hypertrophy
– Hyperplasia
– Atrophy
– Hypoplasia
– Metaplasia
• Relevance of these changes
• Different cell types
• Factors influencing response to injury