This document discusses cell injury and adaptations at the cellular level. It defines cells and their main components. It describes various causes of cell injury including internal deficiencies and external insults. The document outlines different outcomes when a cell is exposed to an injurious agent including adaptation, reversible injury, and irreversible injury leading to cell death. It also discusses different types of cellular adaptations like hypertrophy, hyperplasia, atrophy, metaplasia, and dysplasia that cells undergo in response to stresses or insults.

1. MID 2163
PATHOLOGY

2. TOPIC 2:
CELL INJURY AND
ADAPTATIONS

3. CELL

4. Cell
Basic structural and functional unit in human
body
Human contain almost 100 trillion cells
Different cells in tissues constantly interact
with each other = cell-cell and cell-matrix

5. Cell
3 principle components
– Plasma membrane
– Nucleus
– Cytoplasm

7. GOLGI
CENTROSOME COMPLEX
ENDOPLASMIC
CYTOSKELETON
RETICULUM
CILIA &
10 RIBOSOME
FLAGELLA
ORGANELLES
PROTEASOME LYSOSOME
MITOCHONDRIA PEROXISOME

11. 3 MAIN GROUPS OF CELLS
Labile cells
Stable cells
(unstable)
Rapid proliferation Slow proliferation
and cell turnover and cell turnover
e.g: gut lining & e.g: hepatocytes
epithelial cells
Permanent cells
Not able to proliferate
e.g: neurons

12. CELL
INJURY

13. Cell Injury
Cells are active participants in their
environment
– constantly adjusting their structure &
function to accommodate changing
demands and extracellular stresses
Cells tend to maintain their normal condition
= homeostasis

14. Cell Injury
Cells encounter physiologic stresses or
pathologic stimuli = undergo adaptation
– achieving a new steady state and preserving
viability and function
Ultimate fate of a cell (once exposed to a
harmful stimulus) depends on the type,
severity & duration of the stimulus and also
the type of cells

15. Cell Injury
Example:
– Brain cells, heart cells susceptible to
hypoxia and ischemia
– liver cells susceptible to chemical injury
– Calf muscle tolerates 2-3h of ischemia
– Cardiac muscle dies in 20-30 min

16. Cell Injury
Cell exposed to injurious agents, the
possible outcomes are:
i. The cell may adapt to the situation
ii. The cell may require reversible injury
iii. The cell may obtained irreversible injury and
may die

17. CAUSES
(internal)
Deficiency of Ischaemia =
vitamins, reduced blood
hormones etc supply
Enzyme defects
Immune-mediated
(genetic) e.g.
mechanisms
glactosemia

18. CAUSES
(externally)
Microbial agents: Chemical agents
bacteria, viruses, & toxins
fungi e.g: paraquat
Nutritional
e.g: lead posoning
Physical
e.g: mechanical trauma, atmospheric pressure,
thermal, U.V. light, Ionising radiation

19. Cell Injury
Injury to a certain component in cell will lead
to its dysfunction
The cellular components that are prone to
injury are:
→ Plasma membrane
→ Mitochondria
→ Nucleus
→ Lysosomes

21. Plasma Membrane
Functions:
– Maintain integrity of cell
– Contact with extracellular environment =
cell surface receptors
– Passage of ions (through permeable
channels) & complex molecule (pinocytosis
or phagocytosis)

22. Plasma Membrane
 If the cell injured, blebs of the cellular plasma
membrane noted
– Focal extrusion of the cytoplasm
– Cell detach from the membrane
 Contact with extracellular environment = cell
surface receptors
 Passage of ions (through permeable channels) &
complex molecule (pinocytosis or phagocytosis)

23. Plasma Membrane
Effects of plasma membrane injury:
– Loss of structural integrity - cause cell to
rupture and die
– Loss of function - water enters cells and cause
cloudy swelling hence electrolyte imbalance within
cell
– Deposition of lipofuscin (brown atrophy) -
brown pigments deposited within cytoplasm eg in
myocardial cells and liver cells

24. Mitochondria
Main sites of energy production for cellular
activities
Disorder of energy production affects all
cellular functions
– Mitochondria swell, dissipation
of energy gradient & impairment
of mitochondrial volume
– amorphous densities rich in
phospholipid may appear
= reversible

25. Nucleus
Contains DNA - controls all cellular activities
– Action of at least 1000 genes
– Each encodes a protein with structural, enzymatic
or control functions
Damage to DNA (esp in dividing cells)
– Effective repair mechanisms but severe damage
usually leads to cell death by apoptosis
GERM CELL SOMATIC CELL

26. Germ Cell DNA Damage
Spermatogonia / Oocytes
Less severe damage
Severe damage to to groups of genes
chromosomal structure or single genes

Prevention of conception 
Develomental abnormalities

Early abortion 
Hereditary disease

Susceptibility to disease

27. Somatic Cell DNA Damage
All cells in our body

Acquired during life

Damage to stem cell
Example:
- development of cancer cells through
activation of oncogens or loss
of tumor supressor genes

28. Nucleus
Effects of DNA abnormalities:
– Failure of synthesis of structural proteins
– Failure of mitosis
– Failure of growth-regulating proteins
– Failure of enzyme synthesis

29. Lysosomes
Membrane bound organelles contain
hydrolytic enzymes
– Responsible for digestion and disposal of
complex substances
Disorder may lead to escape of enzymes or
to cellular overloading (storage disorders)

30. Cell Injury
Injury may progress to:
1) Adaptation state
• Mild/persistant injorious agents = recover to
normal state
2) Reversible injury
• Respond to injury but recover
3) Irreversible injury
• Cell respond to injury and cannot recover
(cell death)

31. Cell Injury
If the adaptive capability is exceeded or if
the external stress is inherently harmful
– cell injury develops!
Severe or persistent stress results in
irreversible injury and death of the affected
cells

32. Cell Injury
Cells are stressed so severely
– no longer able to adapt
– exposed to inherently damaging agents
– suffer from intrinsic abnormalities
Different injurious stimuli affect many
metabolic pathways and cellular organelles

34. CELL
ADAPTATIONS

35. CELL ADAPTATIONS
Changes made by a cell in response
to adverse environmental changes
➲REVERSIBLE CHANGES!

36. Cell Adaptations
 2 types of adaptations
1. Physiological adaptations:

usually response of cells to normal
stimulation by hormones or endogenous
chemical mediators

e.g: hormone-induced enlargement of the
breast during pregnancy
1. Pathological adaptations:
 responses to stress that allow cells to
modulate their structure and function and
thus escape injury

37. Cell Adaptations
Cells adapt by altering their pattern of
growth
– Hypertrophy
– Hyperplasia
– Atrophy
– Metaplasia
– Dysplasia
*Within certain limits injury is reversible, and cells
return to a stable baseline

38. Hypertrophy
Increase in the size of cells
– Increased workload  increased protein
synthesize and size & number of
intracellular organells = increased organ's
size
– Happen in cell that cannot be devide
– Reaches limit  no longer able to
compensate = failure & degeneration

39. Hypertrophy
 Example:
– Pathological:
• enlargement of left ventricle in
hypertensive heart disease
– Physiological:
• muscle increase in body builder

43. Hyperplasia
Increase in the number of cells
– Resulting from increase in cell division –
happen in cell that can divide = mitosis
– Compensatory (regeneration) &
hormonal (occurs mainly at organs that
depend on estrogen)

44. Hyperplasia
 Example:
– Physiological:
• enlargement of breast during
pregnancy
– Pathological:
• endometrial hyperplasia

47. Atrophy
Decrease in the size of cells
– Reduced functional capacity, lead to
decrease size of organ
• Formation of autphagic vacuoles
contain cellular debris from degraded
organelles

48. Atrophy

Loss of cell substances due to
 decrease workload
 loss of innervation
 diminished blood supply
 inadequate nutrition
 loss of endocrine stimulation

49. Atrophy
Examples:
– Physiological:
• reduced activity of old age = decrease in size
of skeletal muscle, brain and testis
• Thymus atrophy during early childhood
– Pathological:
• Trauma to a supply nerve root = skeletal
muscle markedly riduced in size following
loss of innervation

52. Normal Adult 82 y.o = atrophy

53. Metaplasia
Replacement of one differentiated tissues
by another differentiated tissues
– adaptive substitution - able to withstand the
adverse environment = reversible!
– Altered differentiation pathway of tissue stem
cells
 May result in reduced functions or increased
propensity for malignant transformation.

54. Metaplasia
Example:
– Squamous metaplasia – replacement of
another type of epithelium with squamous
epithelium
– Osseus metaplasia – replacement of connective
tissue by bone

57. Dysplasia
Abnormality of development
– Morphological transformation – increased in rate
of cell division & incomplete maturation of
resultant cells
– High nuclear to cutoplasmic ratio
Early neoplastic process
Example:
– Epithelial dysplasia of the cervix – detected by a
pap smear