CELLULAR INJURY

DR S S BELLO
PATHOLOGY DEPARTMENT
BAYERO UNIVERSITY, KANO.
Introduction
 Cell Injury occur when cells are stressed so severely that they are no
longer able to adapt or when cells are exposed to inherently amaging
agents or suffer from intrinsic abnormalities.
CELLULAR INJURY
 If the cells fail to adapt under stress, they undergo certain changes called cell injury.
The affected cells may recover from the injury (reversible) or may die (irreversible).
 Causes of Cell Injury
 oxygen deprivation (anoxia)
 physical agents
 chemical agents
 infections agents
 immunologic reactions
 genetic defects
 nutritional imbalances
 Iatrogenic causes
 Idiopathic causes
Important targets
 Aerobic respiration –
 ATP depletion or decreased synthesis.
 Cell membranes - plasma membranes, mitochondrial, lysosomal and
other organelle membranes.
 Protein synthesis.
 Cytoskeleton.
 Genetic apparatus.
Morphology of Reversible cell injury
 Reversible:
 Cellularswelling and vacuole formation (Hyodropic changes)
 Changes at this stage are better appreciated by EM that may show
blebbing of the plasma membrane, swelling of mitochondria and dilatation
of ER
 Fatty changes
NECROSIS AND APOPTOSIS
 NECROSIS: Is focal death along with degradation of tissue by hydrolytic enzymes liberated
by cells. It is accompanied by inflammation.
 Types:
Coagulative necrosis
Liquefactive necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis
Gangrenous necrosis
Mechanism
 Depletion ATP
 Mitochondrial damage
 Calcium influx and loss of homeostasis
 Accumulation of free redicals
 Membrane damage
 Damage to DNA and proteins
Apoptosis
 Form of cell death in which cell destined to die activate intrinsic
enzymes that degrade the cells’ own nuclear DNA and nuclear and
cytoplasmic proteins. It is tightly regulated.
 Also known as programmed cell death

 Causes

1. Physiologic : E.g embryogenesis, elimination of self reactive cells,

involution of hormone dependent tissue, cell loss in proliferating tissues
etc.
 2. Pathologic
 DNA damage

 Accumulation of misfolded proteins

 Cell death in certain infections

 Atrophy in parenchymal organs after duct obstruction

Mechanisms of Apoptosis
 Initiation Phase:
Intrinsic Pathway
Extrinsic Pathway
 Execution Phase
Contrasting features of Necrosis and Apoptosis
NECROSIS
 Cell death along with degradation of tissue
 Caused by hypoxia and toxins
 Inflammation is always present
 Death of many adjacent cells
 Cell swelling
 Membrane disruption
 Nuclear disruption
 Damaged organelles
 Cell death by ATP depletion, membrane
damage , free radical injury
APOPTOSIS
 Programmed and coordinated cell death
by cytotoxic T cell-mediated process
 Caused by physiologic and pathologic
processes
 No inflammatory reaction
 Death of single cells
 Cell shrinkage
 Apoptotic bodies
 Organelles intact
 Chromatin condensation
Necroptosis
 Form of cell death that share both featues of necrosis and apoptosis.
 Morphologically and to some extent biochemically, it resembles
necrosis.
 Mechanistically, it is triggered by genetically programmed signal
transduction events that culminate in cell death.
 Irreversible
 The changes are produced by enzymatic digestion of dead cellular elements,
denatunation of proteins and autolysis (by lysosomal enzymes)
 Cytoplasm - increased eosinophilia

 Nucleus - nonspecific breakdown of DNA leading to

 pyknosis (shrinkage),
 karyolysis (fading) and
 karyorrhexis (fragmentation).
Irreversible cell injury: note that
 if ischemia persists, irreversible injury develops. Irreversible injury is marked by
severe mitochondrial vacuolization, extensive damage to plasma membranes
and swelling of ribosomes. Injury to lysosomal membranes leads to leakage of
lysosomal enzymes into the cytoplasm,
 there is no universal biochemical point of no return, transitions from reversible
injury to cell death.
Free radicals
 Free radicals have a single unpaired electron in the outer orbit. They are
highly reactive with adjacent molecules.
 Are usually derived from oxygen to produce reactive oxygen species,
superoxide, hydroxyl radicals,H2O2,etc.
 Are normally produced during cellular respiration. Protective molecules
include superoxide dismutase, glutathione peroxidase, vitamin E, vitamin C,
catalase.
 Produced in excess, they react with, and damage proteins, lipids,
carbohydrates, nucleic acids.
 These damaged molecules may themselves be reactive species with a chain
reaction being set up with widespread damage.