cell injury pathology
TRANSCRIPT
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Components Of CellInjury
By
Dr.A.Sridhar
MPT(Neurology)
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• What is Cell injury?
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Cell injury
• When the cell is exposed to an injurious agent
or stress, a sequence of events follows that is
loosely termed as CI
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• What are adaptive response?
• What are the consequences due to cell injury?
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• Hypertrophy
• Hyperplasia
•
Atrophy• Metaplasia
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Cellular Changes and its types
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Myocyte Changes
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Hypertrophy
• An increase in the size of cells resulting in
increase in the size of the organ.
• Examples of P & P
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Hyperplasia
• Characterized by an increase in cell number
• Types
– hormonal hyperplasia
• proliferation of the glandular epithelium of the female
breast at puberty and during pregnancy
– compensatory hyperplasia
• hyperplasia that occurs when a portion of the tissue isremoved or diseased
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Guess ?
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Atrophy
•
Shrinkage in the size of the cell by the loss of cell substance
• Causes
–
decreased workload – loss of innervation
– diminished blood supply
–
inadequate nutrition – loss of endocrine stimulation
– aging
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Guess ?
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Metaplasia
• Reversible change in which one adult cell type
(epithelial or mesenchymal) is replaced by
another adult cell type
• cells sensitive to a particular stress are
replaced by other cell types better able to
withstand the adverse environment
• Smokers
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Guess ?
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Autophagy
• is the process in which the starved cell eats its
own components in an attempt to find
nutrients and survive.
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Autophagy
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Cell injury and cell death
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Patterns Of Cell Death
• There are two principal patterns of cell death:
1- Necrosis and
2- Apoptosis
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Mechanism of cell injury
• ATP production
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MECHANISM OF CELL INJURY
1. DEPLETION OF ATP:
. ATP depletion and decreased ATP synthesis areassociated with both hypoxic and chemical
(toxic) injury .
. ATP is required for many synthetic and
degradative processes within the cell.
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MECHANISM OF CELL INJURY cont.
• ATP is produced in two ways.
A- The major pathway is oxidative
phosphorylation of adenosine diphosphate.
B-The second is the glycolytic pathway , which
generate ATP in absence of oxygen using
glucose derived from body fluids or from
glycogen
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MECHANISM OF CELL INJURY cont.
Effects of depleted ATP
a) The activity of the plasma membrane
energy-dependent sodium pump is reduced.
It causes sodium to accumulate intracellularly
and potassium to diffuse out of the cell
causing cell swelling, and dilation of the
endoplasmic reticulum.
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MECHANISM OF CELL INJURY cont.
b) If oxygen supply to cells is reduced, as inischemia, oxidative phosphorylation ceasesand cells rely on glycolysis for energy
production (anaerobic metabolism) resultingin depletion of glycogen stores.
Glycolysis results in the accumulation of lacticacid which reduces the intracellular pH,resulting in decreased activity of many cellularenzymes.
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MECHANISM OF CELL INJURY cont.
c) Failure of the Ca2+ pump leads to influx of Ca2+, with damaging effects on numerouscellular components
d) Ribosomes detach from the RER andpolysomes breakdown into monosomes,leading to reduction in protein synthesis.Ultimately, irreversible damage tomitochondrial and lysosomal membranesoccurs, and cell undergoes necrosis
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MECHANISM OF CELL INJURY cont.
e) In cells deprived of oxygen or glucose,
proteins may become misfolded, and trigger
the unfolded protein response leading to cell
injury and even death.
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MECHANISM OF CELL INJURY cont.
2- Mitochondrial Damage:
. Mitochondria are important targets for all
types of injury, including hypoxia and toxins.
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MECHANISM OF CELL INJURY cont.
- Cells have defense systems to prevent injury
caused by these products.
- An imbalance between free radical-
generating and radical-scavenging systems
results in oxidative stress causing cell injury .
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MECHANISM OF CELL INJURY cont.
Free radical-mediated damage are seen in
- chemical and radiation injury
- ischemia-reperfusion injury- cellular aging, and
- microbial killing by phagocytes.
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MECHANISM OF CELL INJURY cont.
- Free radicals are chemical species that have single unpairedelectron in an outer orbit.
- They are initiated within cells in several ways:
a) Absorption of radiant energy (e.g., ultraviolet light, x-rays).
b) Enzymatic metabolism of exogenous chemicals or drugs .
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MECHANISM OF CELL INJURY cont.
c) The reduction-oxidation reactions that occur during normal metabolic processes. During normal respiration, smallamounts of toxic intermediates are produced; these includesuperoxide anion radical (O2-), hydrogen peroxide (H2O2),and hydroxyl ions (OH).
d) Transition metals such as iron and copper
e) Nitric Oxide (NO), an important chemical mediatorgenerated by various cells, can act as a free radical.
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Necrosis
Necrosis is the type of cell death that occurs
after ischemia and chemical injury
Necrosis is always pathologic
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Apoptosis
• Apoptosis occurs when a cell dies through
activation of an internally controlled suicide
program.
• Apoptosis is designed to eliminate unwanted
cells during embryogenesis and in various
physiologic processes and certain pathologic
conditions
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APOPTOSIS
• Apoptosis is programmed cell death.
• It is a pathway of cell death that is induced by a tightlyregulated intracellular program in which cells destined to die
activate their own enzymes to degrade their own nuclearDNA, nuclear proteins and cytoplasmic proteins.
• The cell's plasma membrane remains intact, but its structureis altered in such a way that the apoptotic cell sends signal to
macrophages to phagocytose it.
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Features of Necrosis and Apoptosis
Feature Necrosis ApoptosisCell size Enlarged (swelling) Reduced (shrinkage)
Nucleus Pyknosis→ karyorrhexis→
karyolysis
Fragmentation into
nucleosome-size
fragmentsPlasma membrane Disrupted Intact; altered structure,
especially orientation of
lipids
Cellular contents Enzymatic digestion; may
leak out of cell
Intact; may be released in
apoptotic bodies
Adjacent inflammation Frequent No
Physiologic or pathologic
role
Invariably pathologic
(culmination of irreversible
cell injury)
Often physiologic, means
of eliminating unwanted
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Causes of Cell Injury
• Hypoxia
• Physical Agents – Mechanical trauma,
– Burns,
– Deep cold
– Sudden changes in atmospheric pressure, – radiation, and electric shock
• Chemical Agents and Drugs
• Infectious Agents e.g. bacteria, fungi, viruses and
parasites.• Immunologic Reactions.
• Genetic Derangements.
• Nutritional Imbalances
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Cellular and biochemical sites of
damage in cell injury
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Functional and morphologic consequences of
decreased intracellular ATP during cell injury.
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THE MORPHOLOGY OF CELL AND
TISSUE INJURY
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A normal cell and the changes in reversible
and irreversible cell injury (necrosis).
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Cellular Aging