The document discusses cell injury, highlighting the concept of homeostasis and cellular adaptation to physiologic stresses which can lead to injury or death when limits are exceeded. It outlines four main types of cellular adaptations: hyperplasia, hypertrophy, atrophy, and metaplasia, detailing their causes and examples. Furthermore, it differentiates between reversible and irreversible cell injury, discusses the causes of cell injury, and explains the mechanisms of cell death including apoptosis and necrosis.

1. CELL INJURY
Prepared by: Prof. O. O. K. Ibrahim

2. INTRODUCTION:
Normal cell is in a fairly narrow range of function
and structure by
1. its genetic programs of metabolism,
differentiation, and specialization.
2. Constraints of neighbouring cells.
3. And availability of metabolic substrates.
It is in a steady state called homeostasis.

3. INRODUCTION CONTD
More severe physiologic stresses and some
pathologic stimuli may result in cellular
adaptation – a new but altered steady state
aim at preserving the viability of the cell.
Cell injury results when the limits of the
adaptive response to a stimulus are exceeded.
Cell death is the ultimate result of cell injury.

4. CELLULAR ADAPTATIONS
The adaptive responses are:
1. Hyperplasia
2. Hypertrophy
3. Atrophy
4. Metaplasia

5. HYPERPLASIA
 Increase in number of cells in an organ or tissue
resulting in increased volume of the organ or tissue.
 Can be physiologic or pathologic
 Physiological can be hormonal (increase in breast
glandular epithelial cells at puberty and during
pregnancy) or compensatory.
 Pathological is caused by excessive (abnormal)
hormonal stimulation (endometrial hyperplasia due to
excessive oestrogen production.

6. HYPERTROPHY
• This refers to an increase in the size of the
cells, resulting in the increase in the size of the
organ.
• Can be physiologic (caused by increased
functional demand) or pathologic (caused by
specific hormonal stimulation).

7. ATROPHY
 Refers to shrinkage in the size of the cells and
ultimately the size of the tissue or organ.
 Can be physiologic (decrease in the size of the
uterus after parturition)
 Usually pathologic and caused by decreased
workload (atrophy of disuse), loss of innervation,
diminished blood supply, inadequate nutrition,
loss of endocrine stimulation, aging, pressure, etc

8. METAPLASIA
• A reversible change in which one adult cell type is replaced by another
adult cell type.
• Examples are:
1. Squamous metaplasia in the respiratory tract as a result of chronic
irritation in smokers (columnar to squamous)
2. Squamous metaplasia in the urinary bladder as a result of chronic
schistosomiasis (transitional to squamous)
3. Squamous metaplasia of the endocervix as a result of repeated
pregnancies (columnar to squamous)
4. Glandular metaplasia in the lower esophagus as a result of reflux of
gastric secretion (squamous to glandular epithelium).
Metaplastic epithelium is at a great risk of malignant transformation

9. CAUSES OF CELL INJURY
• Cells are injured when their adaptive limits are exceeded
by various injurious agents.
• Cell injury can be reversible or irreversible depending on the
nature of the injurious agent, its intensity, duration of
exposure, and the functional residual capacity of the cell.
• Reversible cell injury – it is manifested as functional and
morphologic changes that are reversible if the damaging
stimulus is removed.
• Irreversible cell injury and cell death – the injury becomes
irreversible and the cell can not recover even if the injurious
is removed.

10. CAUSES OF CELL INJURY
1. Oxygen deprivation (Hypoxia and ischemia)
2. Physical agents – mechanical trauma, extremes
of temperature, radiation, electric shock, sudden
changes in atmospheric pressure.
3. Chemical agents and drugs (including toxins)
4. Infectious agents – viruses, bacteria, fungi,
parasites, etc
5. Immunologic reactions – hypersensitivity
reactions and autoimmune diseases

11. CAUSES OF CELL INJURY contd
6. Genetic derangements -
7. Nutritional imbalances – in form of
deficiencies or excesses

12. Mechanisms of cell injury
1. Depletion of ATP
2. Mitochondrial damage
3. Influx of intracellular calcium and loss of
calcium homeostasis
4. Accumulation of oxygen-derived free radicals
5. Defects in membrane permeability

13. Mechanisms of cell death
Apoptosis versus Necrosis
APOPTOSIS
• This is a pathway of cell death that is tightly
regulated.
• It involves intracellular program in which cells
destined to die activate enzymes that degrade
the cells’ own nuclear DNA and nuclear and
cytoplasmic proteins.

14. APOPTOSIS Contd
• It is the mechanism of removing unwanted cells.
• It can be physiological or pathological
Physiological apoptosis:
• Programmed destruction of cells during
embryogenesis
• Hormone-dependent involution in adult
• Elimination of potentially harmful self reactive
lymphocytes.

15. Pathological apoptosis
• Cell death produced by a variety of injurious
agents.
• Cell injury in certain viral diseases.
• Cell death in tumors

16. NECROSIS
• This is another form of cell death.
• It is the spectrum of morphological changes
that cell death in a living tissue.
• It results from denaturation of intracellular
proteins and enzymatic digestion of the cells.
• There are 2 main forms of necrosis depending
on the predominant mechanism.

17. NECROSIS Contd
• Coagulative necrosis
• Liquefactive necrosis (abscess formation)
Variants of coagulative necrosis:
1. Caseous necrosis
2. Gangrenous necrosis
3. Fat necrosis