cell injury, adaptation, & death
TRANSCRIPT
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Cell Injury, Adaptation, &
Death
Tonde MatsungoB.Sc (UZ). M.Phil (UZ)
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Cells
Tissues
Organs
Systems
Organism
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How is meiosis
different?
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Tumor suppressor genes
synthesize growth inhibition proteins
p53
Proto-oncogenes
stimulate cell growth
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Proliferation of Cells
Labile
continuous reproduction
Stable
reproduce slowly until injured
Permanent
no division
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Biologic Aging
Apoptosis
Programmed cell death
Necrosis
Death caused by disease
As cells age, functioning decreases
Genetically, telomeres influence cell aging
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All diseases occur
because of cell injury
Either because of the
injury itself or therepair process that
follows
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Introduction to Pathology
Vocabulary Pathology
Literally it is the study of suffering
What happens to tissues/organs of thebody in the presence of disease
Disease
Literally a lack of ease
Pathological process of the bodyorgan(s) with its own signs andsymptoms
Dysfunction of significant number of cells
in the organ must occur first 14tmatsungo@gmail
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Disorder
Organ is normal but malfunction of theorgan exists
Disease may or may not be present Sickness
The physical and/or mental state of beingunwell
Can be due to emotions, background,inheritance self image, presence orabsence of psychiatric problems, etc.
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Introduction to Pathology
Vocabulary
Health
Well being state indicating normality of
body, mind and spirit Origin in health cells in tissues and organs
Sign
Observable objective or measurablephysical manifestations of disease(s) or
disorder(s)
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Introduction to Pathology
Symptom
Subjective evidence of a disease or
disorder
DiagnosisAttachment of a specific name to a
specific disease or disorder
Summation of signs, symptoms, tissuechanges, chemistry, physiology or
function changes unique to that
disease or disorder
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Introduction to Pathology
Vocabulary Prognosis
Making a prediction of the outcome of adisease or disorder
Therapy Treatment of a disease or disorder
Several components
Supportive lenses
Restorative VTPhysical agents laser
Chemical medications
Surgical18tmatsungo@gmail
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Introduction to Pathology
Etiology
The cause of a disease or disorder
Pathogenesis
Underlying mechanisms resulting inthe signs and symptoms of the patient
Morphology
Gross or microscopic appearance ofcells and tissues
For a disease or disorder to becomemanifested clinically, there first must be adysfunction of a significant number of cellsin an organ or tissue
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Causes of Cell Injury
Hypoxia
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Hypoxia
Inadequate oxygenation
Most common cause of
cell injury
Usually due to ischemia
Causes chemical & acid-
base imbalances
Reversible if O2 restored
or death if not
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Causes of Cell Injury
Hypoxia
Direct physical action
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Direct Physical Action
Major problems arehemorrhage &
ischemia
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Causes of Cell Injury
Hypoxia
Direct physical action
Ionizing radiation
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Ionizing Radiation
Ionizes H2O into H+
& OH-
OH- attaches to
DNA & prevents cellreproduction
DNA mutations
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Causes of Cell Injury
Hypoxia
Direct physical action
Ionizing radiation Toxic molecular injury
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Toxic Molecular Injury
Dose related
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Causes of Cell Injury
Hypoxia
Direct physical action
Ionizing radiation Toxic molecular injury
Microbes
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Microbes
Toxins can
interfere with
protein synthesis
or utilization ofO2
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Causes of Cell Injury
Hypoxia
Direct physical action
Ionizing radiation Toxic molecular injury
Microbes
Inflammatory & immune reactions
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Inflammatory & Immune Reactions
Due to cell injury &
then in turn causes
injury
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Causes of Cell Injury
Hypoxia
Direct physical action
Ionizing radiation
Toxic molecular injury Microbes
Inflammatory & immune reactions
Nutritional imbalances
Genetic defects
Aging
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Mild Cell Injury Hydropic change
Na/K pumpdamaged so Na+
increases in the cell
& H2O moves in
causing swelling
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Intracellular Accumulations
Some due to
phagocytosis or other
normal physiologic
mechanisms
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Fat
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Cholesterol
Most extensive &
damaging
accumulation
Atherosclerosis
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Protein
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Glycogen
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Pigments
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Adaptations
Change in size
Change in number of
cells
Change into another
type of cell
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Overview of Cellular Responses
to Stimuli Cells operate in a very narrow range of
physiologic parameters they maintain
homeostasis
Homeostasis equilibrium of the
microenvironment of the cell
Chemical electrolytes, glucose, pH, etc.
Physical temperature, etc.
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Overview of Cellular Responses
to Stimuli Constantly adjust their structure and function
adapting to their altered environment
Adaptation adjusting to a new situation to
preserve viability and function Stress pathological definition any demand on
the cell requiring it to adapt
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Overview of Cellular Responses
to Stimuli Inability to adapt will compromise the cell
and result in injury and possibly death
Principle adaptive responses
Hypertrophy Hyperplasia
Atrophy
Metaplasia
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Overview of Cellular Responses
to Stimuli If the adaptive capability of the cell is
exceeded or the stress inherently harmful,cell injury occurs
Reversible return to baseline Irreversible
Cell death causes include ischemia,infections, toxins, and immune reactions
Cell death can be a normal and essentialprocess
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Stages in cellular response to
stress and injurious stimuli
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Cell reaction to stimuli
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Overview of Cellular Responses
to Stimuli Other factors that affect stress on the cell
Vulnerability - by location
Differentiation by specific cellular function,
i.e., different cells do different things whichmay predispose to protection or problems
Blood supply better supply, better chance of
survival
State of nutrition
State of cellular health at the time of stress
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Overview of Cellular Responses to Stimuli
Molecular and biochemical levels that stress
may affect Maintenance of cellular membrane
Cell and its components
Trauma, acids, etc.
Maintenance of ionic/osmotic balance
Water, medications, etc.
Energy production by the cell
Protein synthesis nutrition
Genetic apparatus
Viruses, radiation, etc.49tmatsungo@gmail
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Cellular Adaptations to Stress
Adaptations are reversible changes in thenumber, size, metabolic activity, andfunctions of cells
Two basic types Physiologic
Cellular response to normal stimulation
e.g. - hormones
Pathologic Modified cellular response to avoid injury
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Atrophy
Decreased size &function
Metabolic processesshut down toconserve energy
Due to decreased demand
ischemia lack of nerve orhormonal stimulation
chronic inflammation
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Hypertrophy
Increased size &
functional capacity
Due to
hormonal stimulation increased functional
demand
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Hyperplasia
Increase innumber of cells
Due to hormonal
stimulation
increasedfunctionaldemand
chronic stressor injury
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Dysplasia
Disorderly overgrowth
of cells
Premalignant
Reversible
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Metaplasia
One cell type to another
Reversible
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Necrosis
Pathologic cell death
Usually in a collection of cells fed by a
single artery
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Coagulative Necrosis
Most common
Dead cells form a gel-
like consistency
No anatomicdisruption so cells or
tissues are left with a
ghostly outline
Infarction most
common cause
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Liquefactive Necrosis
Dead tissue dissolves
into liquid
Dead cells disrupted
faster than it can becleaned up
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Caseous Necrosis
TB
cheesy
Cellular detail gone
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Fat Necrosis
May due to trauma
Triglycerides
digested & free
fatty acidsprecipitate as
calcium salts
One type of
dystrophiccalcification
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Gangrene
Dry part is dry & shrinks
skin wrinkles
dark brown or black
slow spread
line of demarcation
form of coagulation necrosis extremities
Wet (moist) part cold, swollen, pulseless
moist, black, & under tension
liquefaction occurs
foul odor
no line of demarcation spreads rapidly
death if not stopped
organs & extremities
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Cell Injury and Death
Occurs when cells are unable to adapt to
stress or when they are exposed to
damaging agents or suffer intrinsic
abnormalities Reversible cell injury
Damage reversed when stimulus removed
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Cell Injury and Death
Cell death Injury is irreversible
Two types
Necrosis enzymes leak out oflysosomes and cell is digested.Leakage through cell membraneelicits inflammation. Due to ischemia,
toxins, infections, traumaApoptosis cell kills itself, no
membrane leakage
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Necrosis vs. Apoptosis
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Cell injury
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Subcellular Responses to Injury
Certain agents and stresses can affect
only subcellular organelles
Some are seen in lethal injury, some in
adaptive responses
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Subcellular Responses to Injury
Lysosomes cytoplasmic bodies thatcontain hydrolytic enzymes used to
breakdown phagocytosed material
Autophagydigestion of cells owncomponents
A survival mechanism in times of
nutrient deprivation
Heterophagy ingestion of outsidematerial for intracellular destruction
Example - macrophage68tmatsungo@gmail
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Subcellular Responses to Injury
Induction (hypertrophy) of smooth
endoplasmic reticulum
Involved in metabolism of chemicals
Hypertrophy is adaptive response to chemicalstimuli
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Subcellular Responses to Injury
Example barbiturates and cytochrome P-450 system; swelling occurs to better
metabolize medication but may better
metabolize other medications as well (alcohol)
Mitochondrial alterations
Energy producers in the cell
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Subcellular Responses to Injury
Cytoskeletal abnormalities
Consists of actin and myosin filaments,
microtubules and various filaments that are
altered These structures are responsible for:
Intracellular transport of organelles and
molecules
Maintenance of cell architecture
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Subcellular Responses to Injury
Maintenance of mechanical strength
for tissue integrity
Cell mobility
phagocytosis
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Mechanism of Cell Injury
Cellular response to injurious stimuli depends onthe type of injury, its duration, and its severity
Consequences of the injurious stimulus depends
on the type, status, adaptability, and the geneticmake-up of the injured cell
Striated versus cardiac muscle
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Mechanism of Cell Injury
Cell injury results from functional andbiochemical abnormalities in one or more of
several essential cellular components
Mitochondria Cell membranes
Protein synthesis
Cytoskeletal
Genetic apparatus
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Principle Sites of Damage in
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Principle Sites of Damage in
Cell Injury
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Examples of Cell Injury and
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Examples of Cell Injury and
Necrosis
Ischemia and hypoxic injury
Ischemia
Diminished blood flow to a tissue
Most common cause of cell injury
Compromises delivery of substrates for
glycolysis
Hypoxia Decreased oxygen delivered
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Examples of Cell Injury and
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Examples of Cell Injury and
Necrosis
Ischemia-reperfusion injury
Restoration of blood flow can cause
exacerbated and accelerated injury
Chemical (toxic) injury Chemical may combine with a component of
the cell
Inactive chemical is converted to a reactivetoxic metabolite
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Apoptosis
Cell destroys its own nuclear DNA andnuclear and cytoplasmic proteins
Plasma membrane remains intact
Membrane altered inducing phagocytosis
but no leakage
No inflammation
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Apoptosis
Physiologic
Death of specific cell types at defined times
during development of the organism
Involution of hormone-dependent tissuesupon hormone deprivation
Cell loss in proliferating cell populations
Intestinal crypt epithelia
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Apoptosis
Death of cells that served their purpose
Neutrophils in an acute inflammatory
response
Elimination of potential harmful self-reactivelymphocytes
Prevents reaction against ones own tissue
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Apoptosis
Pathologic
Eliminates cells that are genetically altered or
injured
DNA damage Cell injury in certain infections viruses
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Apoptosis
Examples
Growth factor deprivation
Hormone-sensitive cells deprived of the
hormone Lymphocytes not stimulated by antigens
Neurons deprived of nerve growth factor
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Apoptosis
DNA damage
Exposure to radiation or chemotherapeutic
agents
Self-reactive lymphocytes Lymphocytes that encounter self antigens
Failure of apoptosis here causes
autoimmune diseases
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Cellular Aging
Result of a progressive decline in theproliferative capacity and life span of cells andthe effects of continuous exposure to exogenousfactors that cause accumulation of cellular andmolecular damage
Responsible mechanisms
DNA damage
Occurs during normal replication
Defects in DNA repair mechanismsDNA repair mechanisms can beactivated by caloric restriction
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Cellular Aging
Decreased cellular replication
All normal cells have a limited capacity for
replication
Reduced regenerative capacity of stem cellsAccumulation of metabolic damage
Cellular life span is a balance between
damage from metabolic events and
molecular response that repair the damage