The document discusses cell injury, outlining its definitions, causes, and cellular responses to stress. It categorizes causes of injury into genetic and acquired factors, with acquired causes including hypoxia, physical agents, chemical exposures, microbial agents, and more. The document also describes types of cell injury, adaptive responses, and distinctions between reversible and irreversible injuries.

1. Cell Injury

2. Introduction
General considerations……
• Adapt or die!
• Reaction patterns in a given cell/tissue is often limited
• Degree of injury is a function of type, duration and
severity of insult

3. Definition
 Cell injury: The effect of a variety of stresses due to
etiological agents a cell encounters resulting in changes in
its internal & external environment.
 Cellular response to stress vary & depends upon
1. Host factors: type of cell & tissue involved
2. Factors pertaining to injurious agent : extent & type of
cell injury.

4. Introduction
• Pathology: the study (logos) of suffering (pathos)
• Four aspects of a disease process that form the core of
pathology
1. its cause (etiology)
2. Mechanisms of its development
( pathogenesis)
3. Structural alterations induced in cells &
organs ( morphological changes)
4. Functional consequences of the
morphologic changes ( Clinical significance)

5. Causes of cell injury
 Genetic causes
 Acquired causes -Hypoxia and ischemia
-Physical agents
-Chemical agents and drugs
-Microbial agents
-Immunological agents
-Nutritional derangements
-Psychological factors

6. Causes of cell injury
Acquired causes
1. Oxygen Deprivation
 Ischemia ( loss of blood supply from impeded arterial flow
or reduce venous drainage)
 Local e.g. embolus
 Systemic e.g. cardiac failure
 Hypoxia ( deficiency of oxygen causing cell injury by
reducing aerobic oxidative respiration)
 Oxygen problems e.g. altitude
 Haemoglobin problems e.g. anaemia
 Oxidative phosphorylation
 E.g. cyanide poisoning

7. Causes of cell injury
2. Physical agents
 Direct Physical Effects
- Exposure of tissue to extreme heat or cold
results in direct injury that is often irreversible,
resulting in a pattern of coagulative necrosis.
- Sudden changes in pressure can cause cellular
disruption (e.g. a hammer blow to the thumb).
- Electrical currents can cause direct breakdown
of cellular membranes that may be irreversible.

8. Causes of cell injury
3. Chemical agents & drugs:
Common poisons (arsenic, cyanide, mercury)
interfere with cellular metabolism. If ATP levels
drop below critical levels, affected cells will die.
 The list of pharmaceuticals that may have toxic
effects on cells is enormous. Some act directly, but
most have their effect through breakdown
metabolites. Metabolism of alcohol (a type of drug)
to acetaldehyde is one example.

9. Causes of cell injury
4. Microbial agent
Injuries by microbes include infections caused by Fungi,
Rickettsiae, Bacteria, parasites and Viruses
5. Immunologic agents: Double –edged sword’- protects the
host against various injurious agents but it may also cause
cell injury.
 Hypersensitivity reactions
 Anaphylactic reactions to a foreign body
 Autoimmune diseases

10. Causes of cell injury
6. Nutritional Imbalances:
 Dietary insufficiency of protein, vitamins and/or
minerals can lead to injury at the cellular level due
to interference in normal metabolic pathways.
 Dietary excess
 can likewise lead to cellular and tissue alterations
that are detrimental e.g. fat is the biggest
offender, or excess ingestion of "health
supplements"

11. Causes of cell injury
7. Psychogenic diseases: No specific biochemical or
morphologic changes in acquired mental diseases.
problems of drug addiction, alcoholism & smoking results
in various organic diseases such as liver damage, chronic
bronchitis, lung cancer, peptic ulcer, HT, IHD etc,
8. Genetic derangements: result in a defect as severe as the
congenital malformations associated with down
syndrome, caused by chromosomal abnormalities.
Inborn error of metabolism arising from enzymatic
abnormalities.

12. Causes of cell injury
9. Iatrogenic causes
10. Idiopathic diseases: ‘Unknown cause’. Exact
cause is undetermined.
Most common form of HT ( 90%) is idiopathic
( or essential ) HT.
11. Ageing: it is result of a progressive decline in
the proliferative capacity & life span of cells and
the effects of continous exposure to exogenous
influences that result in progressive
accumulation of cellular and molecular damage.

13. Cellular responses
1. Cellular adaptations
2. Reversible & irreversible cell injury
3. Subcellular changes
4. Intracellular accumulations.

14. Cellular responses
 Adaptive Responses
 Atrophy
 Hypertrophy
 Hyperplasia
 Metaplasia
 Cell Injury
 Reversible
 Irreversible
 Cell death
Necrosis
Apoptosis

16. Adaptation
 In case of severe stress, the narrow range
of alteration in structure & function is not
sufficient, the cell undergoes an altered
but steady state e.g. atrophy, hypertrophy.

17. Cellular responses
1. Cellular adaptations:
 Increased functional demand
↓
cell adapt to the changes
↓
expressed morphologically
↓
revert back to normal after the stressed is
removed.

19. Adaptive response:
 Hypertrophy: An increase in the size of cells
and ,with such change ,an increase in the size of
the organ
( without any change in the number of cells)
Hypertrophied organ has no new cells ,just large
cells.
 Atrophy : shrinkage in the size of the cell
substance is known as atrophy.
 Hypoplasia : Term used for developmentally
small size.
 Aplasia: Extreme failure of development so that
only rudimentary tissue is present.

20. Adaptive response
 Hyperplasia: An increase in number of cells in
an organ or tissue resulting in enlargement of
the organ or tissue.
 Metaplasia: Reversible change in which one
adult cell type ( epithelial or mesenchymal) is
replaced by another adult cell type.
 A regressive change in the adult cells
manifested by variation in their size, shape &
orientation. Commonly associated with chronic
inflammation and irritation or is seen adjacent to
cancerous change. There is tendency to develop
into cancer in some cases.

21. Adaptive response
 Intracellular accumulations : one of the
manifestations of metabolic derangements in
cells is the intracellular accumulations of
abnormal amounts of various substance.
1. A normal cellular constituent- water, lipid,
proteins & carbhohydrates.
2. An abnormal substance
Exogenous : minerals or products of infectious
agents
Endogenous : products of abnormal synthesis
or metabolism
3. Pigments

22. HEART( lipid accumulation)
 lipid accumulation in two forms:
1.Tigroid effect: bands of yellowed myocardium
alternating with bands of darker, red brown
myocardium uninvolved in patients with profound
anemia
2.Diffuse ,uniform appearance of myocardium e.g:
Diphtheritic myocarditis & severe anemia.

23. Cellular responses : Subcellular
changes
 Residual effects of reversible cell injury persist in
cell as evidence of cell injury at Subcellular level
(Subcellular changes) or metabolites may
accumulate within the cell (Intracellular
accumulations).

24. Cellular responses:
Reversible & Irreversible cell injury
Cell injury :
If the cell’s adaptive capability is exceeded or if adaptive response
is not possible, cell injury develops.
 Two types
1. Reversible cell injury ( Degeneration ):stress is mild to
moderate ; injured cell may recover.
2. Irreversible cell injury ( Necrosis ) : Persistent & severe form of
cell injury leads to cell death.

25. Reversible change
 Fatty change ( Steatosis)
Abnormal accumulation of triglycerides within
parenchymal cells.
 Organs:
1.Liver ( common , organ involved in fat
metabolism)
2.Heart
3.Muscle
4.Kidney

26. Fatty change ( Steatosis)
 Causes :
1.Toxins ( Alcohol abuse)
2.DM
3.Protein malnutrition
4.Obesity
5.Anoxia
6.kwashiorkor in children

28. Fatty liver

29. Foam cells
 Accumulation of triglycerides, cholesterol &
cholesterol esters in phagocytic cells.
 Scavenger macrophages, whenever in contact
with the lipid debris of necrotic cells or abnormal
forms of plasma lipids become stuffed with lipid
becoz of phagocytic activities.
 Cytoplasm becomes vacuolated & are called as ‘
FOAM CELLS’. E.g: Atheroslcerosis of aorta

30. ATHEROSLCEROSIS
Fatty dots F.Atheroma Plaques
Complicated

31. Fatty Liver: Microscopy
 Appears as clear vacuoles within parenchymal cells
 D/D: Intracellular accumulations of water &
polysaccharides ( glycogen) produce clear vacuoles.
1. Lipids:
 Avoidance of fat solvents used in paraffin embbeding.
 Frozen section : to identify fat.
 Special stains: Sudan IV, Oil Red- O (orange red ),
Osmic acid, Sudan black( color: black )

32. Fatty Liver: Microscopy
2. Glycogen: PAS ( Periodic Acid
Schiff ) Reaction
3. Water/ Fluid with a low protein
content :
Neither fat nor glycogen can be
demonstrated.

33. Cellular swelling/ cloudy swelling
 Organs: kidney ,liver
 Causes: ischemia, hypoxia, effect of poison.
 Mech : cells are incapable to maintain ionic and
fluid homeostasis.
 Gross: organ is swollen, c/s bulges outwards, pale,
hazy & has a grey parboiled appearance. Soft in
consistency.
 Microscopy: cells are swollen, indistinct cell
margins and cytoplasm filled with
eosinophilic(proteinaceous ) granules and cell
borders might be grayed releasing granules.

34. Reversible cell injury
 Hydropic degeneration :
vacuoles appear in the cytoplasm.
In extreme forms ,cells get distended with fluid &
rupture, resulting in death of cells. e.g. blisters,
 Microvasculature of organ is compressed by
swollen cells ( hepatic sinusoids, capillaries of
renal cortex) resulting in pallor of the organ

35. Irreversible cell injury
 Necrosis: Death of a cell or group of cells in the
midst of living tissue.
1.Coagulative necrosis
2.Liquefactive necrosis
3.Caseous necrosis
4.Fat necrosis
5.Fibrinoid necrosis
6.Gangrenous necrosis
Apoptosis: Programmed cell death.

36. Classification of morphologic forms
of cell injury
1. Reversible cell injury
2. Irreversible cell injury
3. Programmed cell death
4. Deranged cell
metabolism
5. After-effects of necrosis
 Retrogressive changes
 Cell death –necrosis
 Apoptosis
 Intracellular
accumulation of lipid,
protein,
carbhohydrate
 Gangrene, pathologic
calcification.