Cell Adaptations

Dr Tiffany Buhagiar M.D. (Melit.) MSc (Lond)

Objectives
• to address how the body reacts to stressful stimuli in
terms of morphological changes
• be able to define the following terms
Hypoplasia
Atrophy
Hypertrophy
Hyperplasia
Involution
Metaplasia

• explain the mechanisms leading to the morphological

changes
• be able to give examples of each – most occur under
pathological conditions but some are physiological
changes
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Pathology??

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Pathology

• Etiology

• Pathogenesis

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Overview

• Cells are active participants

• Normally maintain homeostasis
• Encounter physiologic stresses or pathologic stimuli
• Adjusting to accommodate such changes

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Cell stress

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Cell stress
o Hypoxia
o Infection
o Immune injury
o Trauma
o Poor nutrition
o Radiation
o Chemicals
o Carcinogens

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Stages in cellular response to stress

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Response to stress

Reactions of cell depends on

• Type of injury
• Duration
• Severity
• Adaptability of the cell
• Physiolgoical condition or pathological condition

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Adaptation Mechanisms

Disorders of Growth Disorders of Differentiation

• Hypoplasia • Metaplasia
• Atrophy
• Hypertrophy
• Hyperplasia
• Involution

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Adaptation Mechanisms

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Adaptation Mechanisms

• Range of cell reactions where cell attempts to adapt

to insult

• Adaptation is the state between a normal unstressed

cell and abnormal injured overstressed cell

• Physiological response to a change in the

environment or response to pathological condition
where adaptation allows the cell to escape injury

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Hypoplasia
-plasia – formation, development

• Decrease in cell size or

• Decrease in number of cells

ONLY DURING DEVELOPMENT

• Secondary to
– reduced proliferation or
– Mismatch of cell replacement and death

• Causes
– Mutations
– Lack of hormones
– Infections e.g. rubella

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Atrophy
• Decrease in cell size or
• Decrease in number of cells
→ smaller tissue or organ

This is usually at a later stage in life than development

Atrophic cells have a diminished functional ability,

reflected in a reduced number of cell organelles

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Atrophy
This adaptive mechanism may be:

• a physiological response or
• a pathological response

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Atrophy - Physiological
Atrophy occurs in

• Normal aspect of aging

– Brain in the elderly

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Atrophy - Physiological
Atrophy occurs in
• Decrease in workload
– E.g. ageing
– E.g. immobility in disuse atrophy of leg muscles

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Atrophy - Physiological
Atrophy occurs in

• Loss of endocrine stimulation

– Uterus at menopause

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Atrophy - Pathological
Atrophy occurs in

• Loss of innervation
– In polio with nerve damage, there is muscle atrophy

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Atrophy
Atrophy occurs in

• Loss of endocrine stimulation

Physiological: e.g. atrophy of the uterus at menopause

Pathological: e.g. thyroid gland atrophy due to

decreased TSH due to pituitary disease

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Thyroid Uterus

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Atrophy - Pathological
Atrophy occurs in

• Diminished blood supply

• Inadequate nutrition – e.g. in Marasmus
• Pressure atrophy – when benign or
malignant tumours press on tissues

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Hypertrophy
• ↑ in the cell size which leads to organ enlargement
• ↑ amounts of structural proteins and organelles
• occurs in cells with limited capacity to divide

Hypertrophy

Physiologic Pathologic

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Hypertrophy

Physiological response due to

• Increased functional demand
– Skeletal muscle hypertrophy associated
with exercise

• Hormonal stimulation
– Pregnancy - oestrogen stimulated
smooth muscle hypertrophy

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Hypertrophy
• Compensatory hypertrophy

– Adjacent to dead cells e.g.

myocardial cells adjacent to an area
of fibrosis

– Viable organ of a pair – e.g. kidney

will hypertrophy if the other is
diseased

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Hypertrophy

Pathological response
• Organs proximal to obstruction or resistance
– Cardiac hypertrophy due to hypertension, valvular
stenosis or insufficiency

– Hypertrophy of bladder
associated with prostatic
gland hyperplasia

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Hypertrophy

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Hypertrophy

There is a LIMIT to hypertrophy, which is then

followed by organ failure

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Hyperplasia
• Increase in the number of cells
• increase in the size of a tissue or organ

• Stopping functional demand or hormonal

abnormality results in reversing the process

Hyperplasia

Physiologic Pathologic

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Hyperplasia

Physiological response

• Increased functional demand

– Female breast at puberty

• Increased hormones
– Proliferative phase endometrium

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Hyperplasia

Compensatory
• To replace lost tissue
– Liver regrowth after partial resection

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Hyperplasia
Pathological hyperplasia
• Benign prostatic hyperplasia
• Cell damage e.g. chronic irritation
• Abnormal increase in hormones
– Adrenal gland hyperplasia in response to
secretion of ACTH by the pituitary gland
• Controlled abnormal increase in hormones
– Endometrial hyperplasia with imbalance of
hormones leading to abnormal menstrual
bleeding

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Hyperplasia

In most organs

• Hypertrophy and hyperplasia occur together and

difficult to separate
• Hyperplasia alone is rare
– Red cell hyperplasia in altitude

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Involusion

• Return of an enlarged organ to normal size

– Thymus involutes as child grows and disappears by mid
twenties
– Uterus involutes after pregnancy to its normal non
pregnancy state

• Retrogression of vital organs and processes at

aging, is called senile involution

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Metaplasia
• Potentially reversible

• Adult differentiated cell type (epithelial or mesenchymal)

replaced by another adult differentiated cell type

• Cells sensitive to a particular stress are replaced by other cell

types better able to withstand the adverse environment

• Arises by reprogramming of stem cells to differentiate along a

new pathway

• Mediated by cytokines, growth factors

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Metaplasia

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Metaplasia - examples

• Bronchial respiratory epithelium to squamous

epithelium
– Seen in habitual cigarette smokers

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Metaplasia - examples
• Gastric epithelium to intestinal epithelium
• Oesophageal epithelium changes to glandular
epithelium (Barrett’s oesophagus)

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Metaplasia - examples
• Cervical glandular epithelium changes to squamous
epithelium

• Occasionally bone in soft tissue injury

Potentially reversible but continued insult leads to risk

of malignancy as protective functions are lost

– Malignant tumour arises from metaplastic epithelium

• Lung, cervical squamous carcinomas

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Dysplasia
• Disorganized growth
• Disorderly but non neoplastic proliferation
• Abnormal cells and abnormal organization of cells
– Atypical cytological alterations of cell size, shape and
nuclear size and shape
– Atypical cytological organization

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Intracellular accumulations
• Cells may accumulate abnormal amounts of various
substances
• Located in the cytoplasm, within organelles or in the
nucleus
• May be synthesized by the affected cells or other
cells

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Intracellular storage
Excess storage
• Fatty change
• Cholesterol and cholesterol esters
• Protein
• Glycogen
• Pigments: lipofuschin, melanin, haemosiderin, bilirubin,
carbon, copper

Calcium deposits
• Physiological
• Pathological - dystrophic, metaplastic
• Ossification

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Intracellular storage

• Normal substances - products of metabolism

• Abnormal substances - due to abnormal metabolism
– e.g. Genetic loss of enzymes

• Indigestible / untransportable material

– Endogenous - lipofuscin, melanin, iron, bile
– Exogenous - carbon, asbestos
– Generally not harmfull but may cause cell injury

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Fatty change
• Triglycerides within liver
parenchymal cells in
– Obesity
– Diabetes
– Hepatitis
– Toxicity - drugs and alcohol

• Non specific change

– Microvesicular or
– Macrovesicular steatosis

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Cholesterol and cholesterol esters
• Atherosclerosis
– In smooth muscle cells,
macrophages in arterial intima

• Hyperlipidaemis xanthomas
– In macrophages in subcutis and in
tendons

• Extracellular cholesterol esters

crystallize as long needles
• Inflammatory conditions

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Pigments - Melanin
• Dark brown pigment

• Produced by dendritic melanocytes in basal skin

• Excess production:
– Exposure to sunlight
– Pregnancy
– Addison’s disease
– Malignant melanoma

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Pigments - Haemosiderin

• Brown granular pigment

• Derived from haemoglobin
• Local excess
– Haemorrhage
– Alveolar macrophages in
cardiac failure

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Pigments - Haemosiderin
• Systemic iron overload
– Increased absorption of dietary iron
– Decreased utilisation of iron
• Haemochromatosis
• Haemolytic anaemia, transfusion

• In hepatocytes and Kupffer cells

• No damage unless severe liver damage

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Pigments - Carbon
• Carbon particles inhaled from polluted atmosphere
• Taken up by alveolar macrophages
• Deposits in draining lymph nodes

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Pigments - Bilirubin
• Normal major bile pigment from haemoglobin
• Excess systemic bilirubin
– Liver disease
– Obstruction of bile outflow

• Deposited in all tissues and fluids

• Prominent in liver and kidneys
• Jaundice - skin and sclerae yellow
• Amorphous green brown globular deposits

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Pigments - Bilirubin

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Calcium deposits
• Physiological calcification
– As seen in aging
– E.g. Costal cartilage and larynx

• Pathological calcification
– Abnormal deposition of calcium and small amounts of iron,
magnesium and other minerals
– Dystrophic calcification
– Metastatic calcification
– Calculi

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Calcium deposits - Dystrophic calcification

• Calcium salts in non viable tissues

– Necrotic tissue - infarcts, fat necrosis, dead parasites, insoissated
pus etc.

• Also found in tendons, valves, tumours, media of aged

arteries
• Normal serum calcium and phosphate

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Calcium deposits - Metastatic calcification
• Widespread deposition in vital normal tissues
• Raised levels of tissue and circulating calcium
– Hypervitaminosis
– Hyperparathyroidism
– Milk-alkali syndrome
– Sarcoidosis

• Excess mobilization of bone calcium

– Prolonged immobilization
– Secondary tumour
– Multiple myeloma

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Calcium deposits - Calculi
• Calcium salts in calculi
– Urinary tract (75% contain calcium)
– Salivary glands
– Biliary tract

• From precipitation of urinary / secretory consistuents

• Deposition favoured by
– Highly concentrated urine / secrerion
– By secretion of excessive amounts of a constituent

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Calcium deposits
Ossification is uncommon bone formation
• Outwith skeletal system
• Secondary to calcification in
– Tumours
– Old haematomas
– Scars

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Question 1

What happened to the thyroid gland if it is

overstimulated by TSH?

a) Atrophy
b) Hyperplasia
c) Dysplasia
d) Neoplasia
e) Hypertrophy

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Question 2
A 51 year old male has a blood pressure of 150/95mm
Hg. If this condition remains untreated for years, which
of the following cellular alterations will be seen in the
heart?

a) Atrophy
b) Hypertrophy
c) Hyperplasia
d) Metaplasia
e) Haemosiderosis

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Question 3
The nonpregnant uterus of a 20 year old female
measured 7x4x3cm. She became pregnant, and just
before delivery of a term infant, the uterus measured
34x18x12cm. Which of the following cellular processes
was the major reason for the increase in the size?

a) Endometrial glandular hyperplasia

b) Myometrial fibroblast proliferation
c) Endometrial stromal hypertrophy
d) Myometrial smooth muscle hypertrophy
e) Vascular endothelial hyperplasia

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Question 4
After several weeks of immobilization of the leg in a
plaster cast, the diameter of the calf often decreases.
This change results from which of the following
alterations in the calf muscles?

a) Atrophy
b) Aplasia
c) Metaplasia
d) Calcification
e) Hypertrophy

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Question 5
After the birth of her first child, a 25 year old female
began breast-feeding. Which of the following
processes has occurred in the breast during
pregnancy that allowed her to nurse the infant?

a) Stromal hypertrophy
b) Lobular hyperplasia
c) Epithelial dysplasia
d) Intracellular accumulation of fat
e) Ductal epithelial metaplasia

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Question 6
Deposition of calcium in the renal tubular epithelium in
patients with primary hyperparathyroidism is the result
of which of the following processes?

a) Dystrophic calcification
b) Renal tubular atrophy
c) Autophagocytosis
d) Metastatic calcification
e) Cellular aging

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Question 7
A 32 year old male experiences heartburn with substernal pain
from reflux of gastric contents into the lower esophagus. After
many months, the esophageal epithelium exhibits the microscopic
appearance shown below. Which of the following pathological
alterations has occurred?

a) Squamous metaplasia
b) Mucosal hypertrophy
c) Columnar epithelial metaplasia
d) Atrophy of lamina propria
e) Goblet cell hyperplasia

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Question 8
The aortic valve seen in the figure was discovered at
the autopsy of a 72 year old male. The heart was
enlarged with marked left ventricular hypertrophy. The
serum chemistry was normal. Which of the following
pathologic processes account for the appearance of
the valve?
a) Amyloidosis
b) Dystrophic calcification
c) Metaplastic calcification
d) Haemosiderosis
e) Fatty change

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