Cellular Adaptations in Disease Faculty of Medicine & Health Sciences Semester 3 Pathology Course P3...

Cellular Adaptations in Disease

Cellular Adaptations in Disease

Faculty of Medicine & Health SciencesSemester 3

Pathology CourseP3

5th October 1999

Prof. James Lowe

Faculty of Medicine & Health Sciences, October 1999

Cellular adaptations in diseaseOverviewOverview

Adaptability of cells to an altered Adaptability of cells to an altered environmentenvironment Physiological and pathological stimuliPhysiological and pathological stimuli

Changes in growth patternChanges in growth pattern Hyperplasia, hypertrophy, atrophy, Hyperplasia, hypertrophy, atrophy,

involution, metaplasiainvolution, metaplasia ApoptosisApoptosis Growth factors Growth factors

Role in altered environmentRole in altered environment


Cellular adaptations in diseaseWhy is this important?Why is this important?

Extremely common responses in diseaseExtremely common responses in disease Certain adaptations in growth act as a Certain adaptations in growth act as a

fertile ground for the later development fertile ground for the later development of neoplasia - cancer formation…of neoplasia - cancer formation…

Nomenclature is used in clinical work.Nomenclature is used in clinical work.


Cellular adaptations in diseaseAdaptability of cells to an altered environmentAdaptability of cells to an altered environment

Cells are constantly exposed to changes Cells are constantly exposed to changes in their environmentin their environment

Cells can adapt to acceptable changes in Cells can adapt to acceptable changes in their environment by modifying their environment by modifying metabolism or growth patternmetabolism or growth pattern

Environmental changes can be Environmental changes can be physiological or pathologicalphysiological or pathological


Cellular adaptations in diseaseExamples of pathological stimuliExamples of pathological stimuli

NutritionalNutritional

ImmuneImmune

EndocrineEndocrine

Physical agentsPhysical agents

Chemical agentsChemical agents

InfectionsInfections

AnoxiaAnoxia

GeneticGenetic


Cellular adaptations in diseaseMetabolic regulationMetabolic regulation

Cells may adapt by metabolic regulationCells may adapt by metabolic regulation Induction of enzymeInduction of enzyme Downregulation of enzymeDownregulation of enzyme Increased synthesis of productIncreased synthesis of product Reduced secretion of productReduced secretion of product

Metabolic adaptation is usually not Metabolic adaptation is usually not associated with morphological changesassociated with morphological changes


Cellular adaptations in diseaseCell stress responseCell stress response

The cell stress response allows cells to The cell stress response allows cells to survive pathological stimulisurvive pathological stimuli Housekeeping genes switched offHousekeeping genes switched off Cell stress genes switched onCell stress genes switched on

Cells stress proteins are expressed in Cells stress proteins are expressed in cells (also called heat shock proteins)cells (also called heat shock proteins)

Cell stress proteins are cytoprotectiveCell stress proteins are cytoprotective


Cellular adaptations in diseaseCell stress proteinsCell stress proteins

Small cell stress proteins act as Small cell stress proteins act as molecular chaperones and prevent molecular chaperones and prevent misfolding of proteinsmisfolding of proteins

Ubiquitin links to damaged proteins and Ubiquitin links to damaged proteins and flags them for elimination by the cellflags them for elimination by the cell

Other groups of cell stress proteins have Other groups of cell stress proteins have roles in the nucleus.roles in the nucleus.


Cellular adaptations in diseaseUbiquitin systemUbiquitin system

Freeubiquitin

Activatedubiquitin

Ubiquitinated protein

Damaged protein

proteosome

Degradedprotein


Cellular adaptations in diseaseIncreased functional demandIncreased functional demand

Increased functional demand can be met by Increased functional demand can be met by two main responsestwo main responses

Increase in cell size: Increase in cell size: hypertrophyhypertrophy Increase in cell number: Increase in cell number: hyperplasiahyperplasia

These may occur independently or together.These may occur independently or together. Reflected by an increase in size and weight Reflected by an increase in size and weight

of an organof an organ


Cellular adaptations in diseasePhysiological hypertrophyPhysiological hypertrophySkeletal muscle hypertrophy in response to exercise


Cellular adaptations in diseasePathological hypertrophyPathological hypertrophyMyocardium in hypertensive heart disease

LV=left ventricle


Cellular adaptations in diseasePathological hypertrophyPathological hypertrophyMyocardium in hypertensive heart disease


Cellular adaptations in diseasePhysiological hyperplasiaPhysiological hyperplasiaEndometrium in the menstrual cycle


Cellular adaptations in diseasePhysiological hyperplasiaPhysiological hyperplasia

Normal uterus

Pregnant uterus


Cellular adaptations in diseasePathological hyperplasiaPathological hyperplasia

Normal skin Hyperplasia after trauma

RP = rete pegDP = dermal papilla


Cellular adaptations in diseaseHyperplasia may be nodularHyperplasia may be nodular

Hyperplasia may occur in a non-uniform Hyperplasia may occur in a non-uniform pattern in an organ or tissue - termed pattern in an organ or tissue - termed nodular hyperplasianodular hyperplasia

Examples includeExamples include hyperplasia of the prostate glandhyperplasia of the prostate gland hyperplasia of the breasthyperplasia of the breast


Cellular adaptations in diseaseNodular hyperplasia of prostateNodular hyperplasia of prostate

From a young man showing uniform texture of gland

From an elderly man showing irregular hyperplastic nodules. This would cause obstruction


Cellular adaptations in diseaseReduced demand for cell activityReduced demand for cell activity

Reduction in the volume of a tissue is Reduction in the volume of a tissue is termed termed atrophyatrophy reduction in cell volumereduction in cell volume reduction in cell numberreduction in cell number

Cell loss is commonly replaced by either Cell loss is commonly replaced by either adipose tissue or fibrous tissueadipose tissue or fibrous tissue

Refelected in a reduced size and mass of Refelected in a reduced size and mass of an organan organ


Cellular adaptations in diseaseCommon causes of atrophyCommon causes of atrophy

DenervationDenervation ImmobilisationImmobilisation Reduced endocrine stimulationReduced endocrine stimulation IschaemiaIschaemia AgeingAgeing


Cellular adaptations in diseasePathological atrophyPathological atrophy

A= atrophic skeletal muscle fibres


Cellular adaptations in diseaseOther causes of a small organ other than atrophyOther causes of a small organ other than atrophy

HypoplasiaHypoplasia: incomplete growth of an : incomplete growth of an organorgan

AgenesisAgenesis: complete failure of : complete failure of development of an organ in development of an organ in embryogenesisembryogenesis


Cellular adaptations in diseasePhysiological atrophy is termed involution Physiological atrophy is termed involution

Most instances of involution are the Most instances of involution are the result of withdrawal of an endocrine result of withdrawal of an endocrine stimulusstimulus

Examples of involutionExamples of involution breast after cessation of lactationbreast after cessation of lactation uterus after parturitionuterus after parturition thyroid after pubertythyroid after puberty


Cellular adaptations in diseaseEvents in cell atrophyEvents in cell atrophy

Cell components are removed by Cell components are removed by degradative systemsdegradative systems cytosolic proteolysis - ubiquitin systemcytosolic proteolysis - ubiquitin system autophagy: elements enwrapped by internal autophagy: elements enwrapped by internal

membrane systems and fused with the membrane systems and fused with the lysosomal systemlysosomal system

Residual lipid material may remain in Residual lipid material may remain in cells as a brown material termed cells as a brown material termed lipofuscinlipofuscin


Cellular adaptations in disease


Cellular adaptations in diseaseReduction in cell number is through programmed cell death

Reduction in cell number is through programmed cell death

Certain trophic signal to cells can lead to Certain trophic signal to cells can lead to a specific form of cell deatha specific form of cell death

Cell death is brought about by precise Cell death is brought about by precise metabolic systemsmetabolic systems

The main type of programmed cell death The main type of programmed cell death is termed is termed apoptosisapoptosis


Cellular adaptations in diseaseApoptosisApoptosis

Normal cells are closely anchored by cell junctions


Cellular adaptations in diseaseApoptosis: first stage...Apoptosis: first stage...

Cells lose contact and round up. There is nuclear condensation.


Cellular adaptations in diseaseApoptosis next stage...Apoptosis next stage...

Apoptotic cell undergoes fragmentation to form apoptotic bodies


Cellular adaptations in diseaseApoptosis final event...Apoptosis final event...

Apoptotic fragments are recognised by local cells and phagocytes, are internalised, and degraded.


Cellular adaptations in diseaseApoptosis biologyApoptosis biology

Cell death pathways exist in the cell Cell death pathways exist in the cell metabolism controlled by the action of metabolism controlled by the action of protease enzymes termed CASPASESprotease enzymes termed CASPASES DNA is cleaved into fragments in between DNA is cleaved into fragments in between

nuceosomes by endonucleasesnuceosomes by endonucleases Protein in cells is cross linked by Protein in cells is cross linked by

transglutaminasestransglutaminases Cell death pathways can be triggered by Cell death pathways can be triggered by

several factors….several factors….


Cellular adaptations in diseaseApoptosis triggers….Apoptosis triggers….

Surface receptor activationSurface receptor activation Surface membrane damageSurface membrane damage Damage to mitochondrial membranesDamage to mitochondrial membranes DNA damageDNA damage

Whether a cell lives or dies depends on the Whether a cell lives or dies depends on the balance between pro-apoptotic and anti-balance between pro-apoptotic and anti-apoptotic factorsapoptotic factors


Cellular adaptations in diseaseChange in cell differentiationChange in cell differentiation

Cells may respond to stimuli by a change Cells may respond to stimuli by a change in terminal differentiationin terminal differentiation

This process is termed This process is termed metaplasiametaplasia


Cellular adaptations in diseaseExamples of metaplasiaExamples of metaplasia

Bladder transitional epithelium (T) with metaplasia to squamous epithelium (S) in response to a bladder stone…


Cellular adaptations in diseaseExample of metaplasiaExample of metaplasia

Urothelium in response to stoneUrothelium in response to stone transitional epithelium to squamoustransitional epithelium to squamous

Respiratory mucosa in response to Respiratory mucosa in response to smokingsmoking Ciliated columnar epithelium to squamousCiliated columnar epithelium to squamous

Connective tissue in response to traumaConnective tissue in response to trauma Collagenous tissue to osseous tissueCollagenous tissue to osseous tissue


Cellular adaptations in diseaseGrowth factorsGrowth factors

Growth factors and their receptors Growth factors and their receptors control cell growthcontrol cell growth

In disease, cell adaptations are controlled In disease, cell adaptations are controlled by the action of growth factors linking to by the action of growth factors linking to nuclear transcription factors via nuclear transcription factors via secondary messenger systems.secondary messenger systems.


Cellular adaptations in diseaseSummarySummary

Cells adapt to altered environmentCells adapt to altered environment Metabolic adaptationMetabolic adaptation Cell stress responseCell stress response Changes in growth patternChanges in growth pattern

Hyperplasia, hypertrophy, atrophy, Hyperplasia, hypertrophy, atrophy, involution, metaplasiainvolution, metaplasia

Growth factors, controlling proliferation Growth factors, controlling proliferation or cell death, play a key role in cell or cell death, play a key role in cell adaptations in diseaseadaptations in disease


Cellular adaptations in diseaseLinks to future work...Links to future work...

Cell biology of apoptosis will be Cell biology of apoptosis will be continued when we consider neoplasia continued when we consider neoplasia and in MM courseand in MM course

Cell biology of growth factors will be Cell biology of growth factors will be continued when we consider healing and continued when we consider healing and repair and will also crop up in study of repair and will also crop up in study of neoplasia.neoplasia.

Cellular Adaptations in Disease Faculty of Medicine & Health Sciences Semester 3 Pathology Course P3...

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