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.
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
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
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
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
20.
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
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
40.
41.
42.
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
45.
46.
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
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
55.
56.
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