Cell Injury, Adaptation, & Death

7/30/2019 Cell Injury, Adaptation, & Death

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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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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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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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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

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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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Hypoxia

Direct physical action

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Direct Physical Action

Major problems arehemorrhage &

ischemia

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Hypoxia


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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Hypoxia


Ionizing radiation Toxic molecular injury

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Toxic Molecular Injury

Dose related

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Hypoxia



Microbes

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Microbes

Toxins can

interfere with

protein synthesis

or utilization ofO2

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Hypoxia



Microbes

Inflammatory & immune reactions

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Inflammatory & Immune Reactions

Due to cell injury &

then in turn causes

injury

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Hypoxia


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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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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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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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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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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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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Induction (hypertrophy) of smooth

endoplasmic reticulum

Involved in metabolism of chemicals

Hypertrophy is adaptive response to chemicalstimuli

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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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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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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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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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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

Documents

Cell Injury, Adaptation, & Death