Cell injury can be reversible or irreversible depending on the severity and duration of the stress. Reversible cell injury involves changes like swelling that can be repaired when the stress is removed, while irreversible injury leads to cell death. Causes of cell injury include hypoxia, radiation, toxins and free radicals. Cells have adaptations like atrophy, hypertrophy, hyperplasia and metaplasia in response to stresses. Neoplasms are abnormal masses of tissue that are benign (non-cancerous) or malignant (cancerous).

1. CELL INJURY AND
ADAPTATION
BY
ALOK BHARDWAJ
Assistant Professor
Ram-Eesh Institute of Voc. & Tech. Education, Greater Noida.

2. DEFINITION: CELL INJURY
“ Cell injury is defined as a variety of stresses a cell
encounters as a result of changes in its internal and
external environment ”
 The cellular response to stress varies and depends
upon the following variables:
 The type of cell and tissue involved
 On extent and type of cell injury
INTRODUCTION

3. CELLULAR RESPONSES TO CELL INJURY
NORMAL
CELL
↑ Functional demand Mild to moderate stress
Severe
p. stress
ADAPTATIONS
REVERSIBLE
CELL INJURY
IRREVERSIBLE
CELL INJURY
ATROPHY,
HYPERTROPHY,
HYPERPLASIA,
METAPLASIA,
DYSPLASIA
DEGENERATIONS,
SUBCELLULAR
ALTERATIONS,
INTRACELLULAR
ADAPTATION
NORMAL CELL
RESTORED
REPAIR AND
HEALING
CELL DEATH
Stress removed Stress removed

5. CAUSES OF CELL INJURYCAUSES OF CELL INJURY

6. HYPOXIA /
ISCHAEMIA
↓ esd cellular generation of ATP
Increased
Glycolysis{Depl
etion of
glycogen)
Damaged
sodium pump
(membrane)
Detachment of
Ribosome's
Pathogenesis of reversible cell injury
↓ Intracellular
pH
↓ esd Protein
synthesis
(RER)
↑Influx of
Ca+2
,H2O, Na
Ultra structural / Functional changes
REVERSIBLE CELL INJURY

7. HYPOXIA /
ISCHAEMIA
↓ esd cellular generation of ATP
synthesis of
membrane
phaspolipid
↑sed Cytosolic
influx of Ca+2
Toxic oxygen free
radicals
Pathogenesis of Irreversible cell injury
CELL DEATH
Phaspholipase activation Protease activation
↑sed loss of membrane
phospholipids
Lipid breakdown
product
Cytoskeletal
injury
Lipid peroxidation
DNA damage
Membrane damage
↓ esd libration of I. E

8. Difference between RI & Irreversible cell
injury

9. In this type of injury plays an important role in the
following situation:
Ischaemia reperfusion injury
Ionising radiation by causing radiolysis of water
Hyperoxia ( toxicity due to oxygen therapy)
Cellular ageing
Killing of exogenous biological agents
Destruction of tumour cells
Chemical carcinogen
Free Radical- Mediated cell injury

10. Generation of Free Radical

11. OH-
Lipid
peroxidation
Protein
oxidation
DNA damage
CELL DEATH
Cytoskeleton
damage
MECHANISM OF CELL DEATH BY HYDROXYL
RADICAL

12. MECHANISM OF CELL INJURY BY IONISING RADIATION
IONISING
RADIATION
Radiolysis
OH-
Proliferating cell Non-proliferating cell
DNA damage Lipid peroxidation
Inhibition of DNA
replication
Cell membrane damage
CELL DEATH

13.  REVERSIBLE CELL INJURY: The following changes
I. Cellular swelling
II.Fathy damage
III.Hyaline damage
IV.Mucoid damage
IRREVERSIBLE CELL INJURY: The following changes
I. Autolysis
II.Necrosis
III.Apoptosis
MORPHOLOGICAL CHANGES DURING CELL INJURY

14. PATHOGENESIS OF FATHY LIVER
DIET ADIPOSE TISSUE
Free fatty acids
Fatty acids
Acetate
Cholesterol esters
phospholipids
Keton bodies
α-Glycero
phosphate
Triglycerides
Lipid acceptor
protein
lipoprotein
Plasma lipoprotein
11
2
3
4
5
6

15. In fatty liver, intracellular accumulation of
triglycerides can occur due to defect at one or more of
the following steps in the normal fat metabolism:
 Increased entry of free fatty acid into the liver
 Increased synthesis of fatty acids by the liver
 Decreased conversion of fatty acids into ketone
bodies
Block in the excretion of lipoprotein from the liver
into plasma
 Decrease synthesis of lipid acceptor protein
Increased glycerophaspate

16. Types of Necrosis
• Liquefactive necrosis: Necrosis in brain,
abcesses cavity.
• Coagulative necrosis:: Necrosis of kidney,
liver, or heart muscle
• Caseous necrosis: Infection with
Mmycobacterium tuberculosis
• Fat necrosis: acute pancreatic necrosis,
traumatic necrosis

17. Major Signs of Necrosis Similar to Apoptosis
1) Nuclear degeneration
‑ Chromatin clumping
‑ Karyopyknosis (shrinking)
‑ Karyolysis (dissolution of chromatin)
‑ Karyorrhexis (fragmentation of chromatin)
2) Cytoplasmic changes

20. Apoptosis is a form of ‘ coordinated and internally
programmed cell death’ which is of significance in variety
of physiologic and pathological conditions.
Apoptosis is a Greek word meaning’ falling off’ or ‘dropping
off’
PATHOLOGICAL CHANGES:
1. Involvement of single cells
2. Shrinkage of cells
3. Convolution of cell membrane with formation of apoptotic
bodies
4. Chromatin Condensation
5. Acute inflammatory reactions
6. Phagocytosis
APOPTOSIS

21. MOLECULAR MECHANISM OF APOPTOSIS
Initiator of apoptosis
Transmembranous, intracellular
Regulator of apoptosis
( BCL-2, Other)
Programmed cell death
FAS receptor activation
(cytotoxic T cell)
FAS receptor activation
(cytotoxic T cell)
Ceramide
TP53
BAX
Mitochondrial injury
DNA damage
APOPTOSIS PHAGOCYTOSIS

22. DIFFERENCE BETWEEN APOPTOSIS & NECROSIS
APOPTOSIS NECROSIS
Coordinate & programmed cell
death
Physiological & pathological agent
Morphology:
No inflammatory reaction
Single cell death
Cell shrinkage
Cytoplasmic blebs on membrane
Molecular changes:
Lysosome & other organelles intact
Genetic activation
Cell death along with degradation of
tissue by hydrolytic enzyme
Hypoxia/ Ischaemia & bacterial toxin
Morphology:
Always inflammatory reaction
Death may adjacent cells
Cell swelling
Membrane disruption
Molecular changes:
Lysosome are break down with
libration of hydrolytic enzyme
Cell death by ATP depletion,
membrane damage, injury

23. Cellular Adaptation
Cells are the structural and functional units of tissues and
organs. They are capable of adjusting their structure and
functions in response to various physiological and
pathological conditions. This capability is called cellular
adaptation.
Cellular adaptations include:
Atrophy--shrinkage of cells
Hypertrophy--increase in the size of cells which results in
enlargement of the organs
Hyperplasia--increased number of cells in an organ or
tissue
Metaplasia--transformation or replacement of one adult
cell type with another
Cellular Adaptation

24. Reduction of number and size of parenchymal cells of
organ or its parts which was once normal is called
atrophy
ATROPHY
CAUSES OF ATROPHY
A. Physiological atrophy
Example:
I. Atrophy of lymphoid tissue in
lymph node & thymus
II. Atrophy of gonads after
menopause
III. Atrophy of brain
B. Pathological atrophy
1.Starvation atrophy
2.Ischaemic atrophy
3.Disuse atrophy
4.Neuropathic atrophy
5.Endocrine atrophy
6.Idiopathic atrophy

25. It is defined as an increased in the size of an organ, tissue
or cell due to increased in size or bulk of the cells but not
the no, of cells.
The hypertrophy is always in response to mechanical
stimulus & mostly effects the muscular tissue or the
muscle having tendency of multiplication.
CAUSES:
1. Smooth muscles hypertrophy due to regular exercise in the body
builders
2. Cardiac muscles hypertrophy due to systemic hypertension;
aerotic valve diseases; Anaemia
3. Smooth muscles hypertrophy of uterus during pregnancy
4. Hypertrophy may be physiological or pathological. In both
cases, it is caused either by increased functional demand or by
hormonal stimulation.
HYPERTROPHY

26. A. Physiological hypertrophy: Enlarged size of the
uterus in pregnancy is in an excellent example of
physiological hypertrophy
B. Pathological hypertrophy: Example of certain
diseases associated with hypertrophy are as under:
i. Hypertrophy of cardiac muscle may occur in a number
of cardiovascular diseases. A few examples producing
left ventricular hypertrophy are: hypertension, aortic
valve disease
ii. Hypertrophy of smooth muscle e.g. cardiac disease,
pyloric disease, hypertension
iii. Hypertrophy of skeletal muscle e.g. hypertrophied
muscles in athletes and manual labourers

27. It is absence of development of an organ with
presence of rudiment.
e.g. Aplasia of lungs with rudimentary bronchus
CAUSES:
Genetic cause : e.g. Chromosomal aberration
Environmental cause: e.g. teratogenic drugs &
chemical,
Antiepileptic drug e.g. Phenytoin, Foliate antagonist,
alcohol
APLASIA

28. It is defined as a reversible change of one type of
epithelial or mesenchymal adult cells to another type
of adult epithelial or mesenchymal cells, usually in
response to abnormal stimuli and often reverts back
to normal on removal of stimulus.
However, if the stimulus persists for a long time,
epithelial metaplasia may transform to cancer. It is of
two type:
1. Epithelial Metaplasia
Squamous ep. metaplasia
Columnar ep. metaplasia
2.Mesenchymal metaplasia
METAPLASIA

29. Dysplasia means ‘ disordered cellular development’ often
accompanied with metaplasia and hyperplasia
Dysplasia occur most often in epithelial cells.
Epithelial dysplasia is characterized by cellular
proliferation and cytologic changes. These changes
include:
I. Increase no of layers of epithelial cells
II.Disorderly arrangement of cells from basal layer to the
surface layer
III.Los of basal polarity i.e. nuclei lying away from basement
membrane
IV.Cellular and nuclear pleomorphism
V.Increased mitotic activity
DYSPLASIA

30. DIFFERENCES BETWEEN METAPLASIA & DYSPLASIA
METAPASIA DYSPLASIA
Definition:
Change of one type of epithelial
or mesenchymal cell
Type:
Epithelial & mesenchymal
Tissue effected:
Bronchial mucosa uterine
endocervies
Cellular changes:
Mature cellular devlopment
Natural history
Reversible on withdrawal of
stimulus
Definition
Disordered cellular devlopment
Type:
Epithelial only
Tissue effected:
Uterine cervix, bronchial mucosa
Cellular changes:
Disordered cellular developments
May regress on removal of itching
stimulus

31. Intracellular accumulation of substances in abnormal amounts can
occur within the cytoplasm ( especially lysosomes) or nucleus of the
cell. This procees was known as infiltration
Intracellular accumulation of the substance is mild degree causes
reversible cell injury while more severe damage results in irreversible
cell injury.
Abnormal intracellular accumulation can be divided into three
groups:
1. Accumulation of constituents of normal cell metabolism
produced in excess e.g. accumulation of lipids, protein &
carbohydrate
2. Accumulation of abnormal substances produced as result of
abnormal metabolism due to lack of some enzymes e.g. storage
disease or inborn error of metabolism
3. Accumulation of pigments e.g. endogenous & exogenous pigments
INTRACELLULAR ACCUMULATION

32. Neoplasm is a mass of tissue that grows faster than
the normal in uncoordinated manner & continuous to
grow after the initial stimulus has seased.
Neoplasm are classified on the basis of their tissue of
origin
1. Malignant or
2.Non-malignant (Benign)
NEOPLASM

33. DIFFERENCE B/N BENIGN & MALIGNENT
BENIGN MALIGNENT
MACROSCOPIC
a. Circumference:
Spherical or ovoid in shape,
well developed
b. Surrounded tissue:
 Often compressed
c. Size: usually small
MICROSCOPIC
a. Features: Resembles with the
tissue of origin
b. Cytoplasm: normal
constituents present
MACROSCOPIC
Irregular in shape poorly well
defined
Usually invade
Large
Poorly resemble with the
tissue of origin
Normal cytoplasm absent

34. BENIGN MALIGNENT
Hperchromatism: Absent
Growth rate: Slow growth
Local invasion:
Often compressed the
surrounding tissue
Metastasis: absent
Recurrence in rare
Presence
Rapid rate
Invades the adjacent tissues
Present
Recurrence in common

35. Chemical carcinogen e.g. Aniline dyes, asbestos,
Cigrate smoke
Radiation carcinogen e.g. x-ray, radioactive isotopes
& UV rays
Oncogenic Virus: Hepatitis – B Virus, human
papiloma virus (HPV)
Effect of Tumor
Pressure effects
Hormonal effects
Cachexia
CAUSES OF NEOPLASM

36. GENERATION OF NEOPLASTIC CELL
Indirect-acting carcinogen
Direct-acting carcinogen
Metabolic activation
Metabolic activation
TARGET CELL
Reactive electrophiles
Target molecules
(chiefly DNA)
Target
molecules
(chiefly DNA)Clonal proliferation of
altered cells
NEOPLASTIC CELL