1. Reversible cell injury involves mild damage that is reversible if the stimulus is removed and causes changes like swelling, fatty changes, and pigment accumulation. 2. Irreversible injury leads to cell death through apoptosis or necrosis. Apoptosis is programmed cell death without inflammation while necrosis is unregulated cell death that triggers inflammation. 3. The document describes the patterns of cellular changes seen in reversible injury including swelling, fatty changes, and pigment accumulation as well as the differences between apoptosis and necrosis.

1. TOPIC 2:
CELL INJURY AND
ADAPTATIONS

2. REVERSIBLE
INJURY

3. Reversible Injury
Early stages of injury = mild
 Mild damage to cell components
including the energy supply
 Cell developed morphological changes

4. Reversible Injury
The functional and morphologic changes are
reversible if the damaging stimulus is
removed
– Significant structural and functional
abnormalities
– Injury typically not progressed to severe
membrane damage and nuclear dissolution

5. Reversible Injury
Causes:
– Hypoxia = reduced oxydative
phosphorilation
– ATP depeletion
– Damaged plsma membrane

7. Reversible Injury
The pattern of cellular changes:
1. Cellular swelling
2. Cellular fatty changes
3. Accumulation of pigments – melanin,
bilirubin, iron

8. 1. Cellular Swelling
 Manifestation of all forms of injury
 Difficult to appretiate with the light
microscopic = electron microscope
– Apparent at the level of the whole organ

9. 1. Cellular Swelling
 Pathogenesis
1. Plasma membrane damaged
– 2. Diminished ATP & Na+ pump
– 3. Na+ increase in cell
– 4. Water rush into cell

10. 1. Cellular Swelling
 Cells unable to maintain ionic and fluid
homeostasis
 Morphological changes
1. Cloudy swelling
2. Hydrophic vacuolation

11. 1. Cellular Swelling
1. Cloudy swelling
– = cells swell, cytoplasm contains coarse granules
– = swelling of the membrane bound organnelles –
mitochondria (rounded & beaded)
2. Hydrophic vacuolation
= cytoplasm contains small watery vacuoles
= vacuoles represent distended and pinch off or
sequestered segments of the ER

13. 1. Cellular Swelling
Examples of the morphological changes:
– Following acute cell injury cells are swollen up and
cytoplasm is granular
– Parenchymatous organs e.g. liver and kidney, are
swollen, bulges when cut and has a grey parboiled
appearance and is soft in consistensy
– The cells assume hydropic or vacuolar when the
cell swelling is marked e.g. baloon cells in
epidermis in herpes simplex infection
– The name cloudy swelling refers to appearance of
the cell under microscope

14. 2. Fatty Changes
 Accumulation of fat in non-fatty tissues
 Usually seen in the parenchymatous organs
(e.g: liver & kidney), skeletal muscles and
heart
 Causes:
– Cell poison: alcohol, chloroform, bacterial
– Clinical disorders: anoxia, diabetes mellitus,
malnutrition, obesity

15. 2. Fatty Changes
 Essential problem: non-fatty tissue unable
to metabolise the amount of lipid present
in them
= fat accumulate within cells!

16. 2. Fatty Changes
 These etiologies cause accumulation of fat in the
hepatocytes by the following mechanisms:
a. Increased uptake of triglycerides into the
parenchymal cells
b. Decreased use of fat by cells
c. Overproduction of fat in cells
d. Decreased secretion of fat from the cells

18. 2. Fatty Changes
Effects of fatty changes
» impaired cellular function = due to the
pathological process causing the fatty changes,
NOT the physical presence of fat within the cell
 Liver - very large accumulation of fat do not impair
basic liver functions
 Rapid or large + fatty myocardium – weak muscle
fibers = dilatation of fat = cardiac failure

19. Increased fat deposition
= enlargement of the organ

20. 3. Accumulation of
pigments
 Pigments can be exogenous or endogenous
– Endogenous pigments include melanin, bilirubin,
hemosiderin, & lipofuscin
– Exogenous pigments include carbon = from
outside
 These pigments can accumulate inside cells in
different situations

21. a. Melanin
 Melanin is a brownish-black pigment
produced by the melanocytes found in the
skin
 Increased melanin pigmentation is caused
by suntanning & certain diseases e.g.
nevus, or malignant melanoma
 Decreased melanin pigmentation is seen in
albinism & vitiligo

25. b. Bilirubin
 Bilirubin is a yellowish pigment, mainly
produced during the degradation of
hemoglobin
 Excess accumulation of bilirubin causes
yellowish discoloration of the sclerae,
mucosae, & internal organs = called
jaundice
– Causes of jaundice = haemolytic anemia, billiary
obstruction & hepatobilliary diseases

27. c. Hemosiderin
 Hemosiderin is an iron-containing pigment
derived from ferritin
 Hemosiderin exists normally in small
amounts within tissue macrophages of the
bone marrow, liver, & spleen as physiologic
iron stores
 It accumulates in tissues in excess amounts
in certain diseases = iron overload disorder

29. c. Hemosiderin
 2 types of hemosiderin accumulation
– Hemosiderosis
• accumulation is primarily within tissue
macrophages & not associated with tissue
damage

32. c. Hemosiderin
 2 types of hemosiderin accumulation
– Hemochromatosis
• more extensive accumulation of hemosiderin,
often within parenchymal cells, which leads to
tissue damage, scarring & organ dysfunction

34. d. Hemoglobin
 Intravascular haemolysis
– Acute
• Appears in urine = dull red color - hematuria
– Chronic
• Paroxysmal haemoglobinuria

35. e. Lipofuscin
 Yellowish brown pigment with a high lipid
content
 Generated by the normal intracellular
metabolism of old cellular components =
such as old cell membranes

36. e. Lipofuscin
 Often found in atrophic cells or in old age
– common in the heart muscle, where the
term “brown atrophy” of the heart is often
applied
– also found in liver cells, testes and nerve
cells

38. e. Lipofuscin
 Seen adjacent to the cell nuclei
(perinuclear location)
– electron microscope = lipofuscin is usually
seen in phagolysosomes (membrane-bound
vesicles that contain old cellular debris)

39. Exogenous Pigmentation
 develop when small amounts of a foreign
substance are embedded in the tissues
 Introduced by inhalation, ingestion or
injection

40. Exogenous Pigmentation
 Inhalation
– coal dust (carbon) - black, stone dust
(silica) – grey, iron, asbestos
– particles reach alveoli - disturb broncial
cilliary action
– produce occupational lung disease =
pneumoconiosis

43. Exogenous Pigmentation
 Ingestion
– Chronic ingestion of metal = silver or lead
– Skin has metallic hue, blue line appears on
the gum (interaction between lead &
hydrogen sulphide)

44. Argyria

45. Excessive intake of carrots = lead to yellowish red
skin pigmentation by carotene

46. Exogenous Pigmentation
 Injection
– Tatooing
• pigments like Indian ink ,cinnabar and
carbon are introduced into the dermis
• the pigment is taken up by
macrophages and lies permanently in
the connective tissue

49. IRREVERSIBLE
INJURY

50. Irreversible Injury
Cell death
With continuing damage - injury becomes
irreversible - cell cannot recover = dies
There are 2 types of cell death
– Apoptosis
– Necrosis

53. Apoptosis
Greek word = falling off, like leaves from
trees in autumn
Programmed cell death
Active, energy dependant
A form of cell death in which a programmed
sequence of events leads to the elimination of
cells without releasing harmful substances into
the surrounding area

54. Apoptosis
Prearranged pathway of cell death
Triggered by variety of specific extracellular and
intracellular signals
Part of the balance between life and death of a cell
– determine that a cell dies when it is no longer
useful or when it may harm the larger organism
– Self-defence mechanism - cell infected by
pathogens or have genomic alteration = cell
destroyed

55. Apoptosis
Rapid process – usually affecting single cells
scattered in a population of healthy cells
– Cells can be eliminated with minimal disruption to
adjacent cells
– Injurious agents that are capable of producing
necrosis can induce apoptosis when given in low
dosage
End result: elimination of cells from tissues
without eliciting a tissue response to injury =
no inflammatory response!

56. Apoptosis
Important process in health and disease =
eliminate unwanted or abnormal cells
– In health: embryogenic and development
• Loss of autoreactive response of T cells in
the thymus = preventing auto-immune attack
• Cyclical hormonal changes of the breast and
endometrial tissue

57. Apoptosis
– In disease:
• irradiation, viral, infection, action of
cytotoxic T cells = rejection of transplanted
organs
• Tumors = apoptosis & proliferation rates
together to control the rate of growth –
tumors with high apoptosis rate generally
grow slowly

58. Apoptosis
2 stages in apoptosis
1)The dying process
 Active metabolic changes in the cell, cause
cytoplasmic and nuclear condensation and
fragmentation
 Plasma membrane intact
 Cell disintegrates into apoptotic bodies – each
surrounded by a plasma membrane and some
contain nuclear material

59. Apoptosis
2 stages in apoptosis
2)The elimination process
– Phagocytosis by surrounding cells followed by
rapid digestion
*The surrounding cells move together to fill the vacant
space, leaving virtually no evidence of the process
*The presence of intact plasma membranes arround the
apoptotic bodies explain the absence of inflammation

62. Necrosis
Greek word = dead, the stage of dying
Major pathway of cell death
Only occur in living organisms
Almost always detrimental and can be fatal
morphologic changes that following the cell
death in a living tissue or organ resulting from
the progressive degradative activity of
catalytic enzymes

63. Necrosis
Causes
– Hypoxia
– Physical agents (trauma)
– Chemical agents (free-radicals)
– Immunological injury (hypersensitivity)

64. Pathogenesis
a) begins with an impairment of the cell’s ability to
maintain homeostasis
b) Leading to an influx of water and extracellular ions
c) Intracellular organelles, most notably the
mitochondria, and the entire cell swell and rupture
(cell lysis)
d) Due to the ultimate breakdown of the plasma
membrane, the cytoplasmic contents including
lysosomal enzymes are released into the extracellular
fluid
e) Therefore, in vivo, necrotic cell death is often
associated with extensive tissue damage resulting in
an intense inflammatory response

66. Necrosis
Nuclear changes
 Pyknosis: condensation of chromatin of
chromatin and shrinkage of the nucleus
 Karyorrhexis: fragmentation of the nucleus
 Karyolysis: dissolution of the nucleus

68. Necrosis
Causes
– Hypoxia
– Physical agents
– Chemical agents
– Immunological injury

71. APOPTOTIC
CELL
NECROTIC CELL

72. Necrosis
Types
– Coagulative necrosis
– Liquefactive necrosis
– Fat necrosis
– Caseous necrosis
– Fibrinoid necrosis