Transcript CELL ADAPTATIONS CELL INJURY CELL DEATH DR.SAMINA

CELL ADAPTATIONS
CELL INJURY
CELL DEATH
DR.SAMINA QAMAR
AP PATHOLOGY.
OBJECTIVES
Understand the concepts of cellular growth
adaptations---Hyperplasia, Hypertrophy,
Atrophy, Metaplasia, Dysplasia
Reversible, irreversible cell injury
OBJECTIVES
Understand the pathologic mechanisms at
the SUB-cellular level---ATP,
Mitochondria, Ca++, Free Radicals,
Membranes
Understand and differentiate the concepts
of APOPTOSIS and NECROSIS
Understand SUB-cellular responses to
injury---Lysosomes, Smooth endoplasmic
reticulum, Mitochondria, Cytoskeleton
OBJECTIVES
Identify common patterns of cellular
swelling and fatty change.
Cell aging
To maintain a steady state of structure
and function is
HOMEOSTASIS
Cellular response to injury
• Non-lethal injury: cell will adapt
• Hypoxia, chemical injury, infection:
Reversible injury will result in fatty change.
Irreversible injury will result in death
• Repeated Injury: cellular aging
ADAPTATIONS: Non-lethal
injury.
• Altered/changed steady state in structure
and function of cell.
• WHY: In response to physical/
pathological stimuli. Increased or
decreased stimulation or any irritation.
The –plasia brothers
• HYPER• HYPO- (A-)
• NORMO-
• META• DYS• ANA• “Frank” ANA-
HYPER-PLASIA
IN-CREASE IN NUMBER OF CELLS, if they can divide.
Examples:
Endometrium,breast,liver.
The –trophy brothers
• HYPER• HYPO- (A-)
• DYS-
HYPER-TROPHY
IN-CREASE IN SIZE OF CELLS
Examples:Myocardium,
Myometrium, Muscle
Hypertrophy v/s Hyperplasia.
Can both occur simultaneously?
A-TROPHY*?
DE-CREASE IN SIZE OF CELLS? YES
IN CELL SIZE DUE
TO LOSS OF CELL
SUBSTANCE
SHRINKAGE
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•
•
•
•
ATROPHY
DECREASED WORKLOAD
DENERVATION
DECREASED BLOOD FLOW
DECREASED NUTRITION
AGING (involution)
PRESSURE
“EXHAUSTION”
Examples: Brain, Muscle.
METAPLASIA
• A SUBSTITUTION of one NORMAL
CELL or TISSUE type, for
ANOTHER
– COLUMNAR SQUAMOUS (Cervix)
– SQUAMOUS COLUMNAR
(Esophagus)
– FIBROUS BONE
–WHY?
Examples: Respiratory epithelium,
Barrett’s, myositis ossificans.
Dysplasia: disorganized
epithelium.
Dysplasia:
Normal-hyperplasia-dysplasiacarcinoma.
CELL DEATH
CELL DEATH
What is DEATH?
–DEATH is IRREVERSIBLE
–But in cell its either
reversible or irreversible.
• APOPTOSIS vs. NECROSIS
REVERSIBLE
CHANGES
• REDUCED oxidative
phosphorylation
• ATP depletion
• Cellular “SWELLING”
IRREVERSIBLE
CHANGES
• MITOCHONDRIAL
IRREVERSIBILITY
• IRREVERSIBLE
MEMBRANE DEFECTS
• LYSOSOMAL DIGESTION
REVERSIBLE = INJURY
IRREVERSIBLE = DEATH
SOME INJURIES CAN LEAD
TO DEATH IF PROLONGED
and/or SEVERE enough
CELL DEATH
• APOPTOSIS (“normal”
death) programmed death.
• NECROSIS (“premature”
or “untimely” death
Death is of two types
INJURY CAUSES (REVERSIBLE)
Hypoxia, (decreased O2)
PHYSICAL Agents
CHEMICAL Agents
INFECTIOUS Agents
Immunologic
Genetic
Nutritional
CHEMICAL INJURY
• “Toxic” Chemicals, e.g CCl4
• Drugs, e.g tylenol
• Dose Relationship
• Free radicals, organelle, DNA
damage
INJURY MECHANISMS (REVERSIBLE)
DECREASED ATP
MITOCHONDRIAL DAMAGE
INCREASED INTRACELLULAR
CALCIUM
INCREASED FREE RADICALS
INCREASED CELL MEMBRANE
PERMEABILITY
What is Death?
What is Life?
•DEATH is
–IRREVERSIBLE MITOCHONDRIAL
DYSFUNCTION
–PROFOUND MEMBRANE
DISTURBANCES
LIFE is……..??? Till death hasn’t
occurred.
DEATH:
ELECTRON MICROSCOPY
B-Microvillus incorporated in cell,
Blebs extruded from cell.
C- Mitochondrial swelling.
DEATH:PINK IN
LIGHT MICROSCOPY
Nuclei
LIQUEFACTIVE
NECROSIS, BRAIN
FIBRINOID NECROSIS
APOPTOSIS: falling off.
•NORMAL
(preprogrammed)
•PATHOLOGIC
(associated with
Necrosis)
“NORMAL” APOPTOSIS
• Embryogenesis
• Hormonal “Involution”
• Cell population control, e.g.,
“crypts”
• Post Inflammatory “Clean-up”
• Elimination of “HARMFUL” cells
• Cytotoxic T-Cells cleaning up
“PATHOLOGIC”
APOPTOSIS
• “Toxic” effect on cells, e.g.,
chemicals, pathogens
• Duct obstruction
• Tumor cells
• Apoptosis/Necrosis spectrum
APOPTOSIS
MORPHOLOGY
• DE-crease in cell size, i.e., shrinkage
• IN-crease in chromatin concentration,
i.e., hyperchromasia, pyknosis
karyorhexis karyolysis
• IN-crease in membrane “blebs”
• Phagocytosis
SHRINKAGE/HYPERCHROMASIA
Karryorhexis, karryolysis.
PHAGOCYTOSIS
Damaged/necrotic cells can
accumulate fat: Fatty change
• Commonly occurs in Liver, heart.
• Due to defective uptake, catabolism or
secretion of lipid.
• Severe fatty change can alter cellular
structure and function.
• Seen in diabetes, alcoholism, obesity.
LIPID LAW
•ALL Lipids are
YELLOW grossly
and WASHED out
(CLEAR)
microscopically
FATTY LIVER
FATTY LIVER
CELL AGING
• It is due to progressive decline in cellular
function resulting from exposure to
exogenous influences.
• Cell can undergo limited number of
divisions and goes into non-dividing or
senescence phase.
• Accumulation of metabolic and genetic
changes that damage DNA.
TELOMERES
• Telomeres are sequences of DNA present
at ends of chromosomes. They become
shorter with every division.
• Once shortened they cannot protect ends
of chromosome and appear as damaged
DNA.
• Cell goes into cell cycle arrest.