Post on 28-Mar-2015
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
Faculty of Medicine & Health Sciences, October 1999
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.
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseaseExamples of pathological stimuliExamples of pathological stimuli
NutritionalNutritional
ImmuneImmune
EndocrineEndocrine
Physical agentsPhysical agents
Chemical agentsChemical agents
InfectionsInfections
AnoxiaAnoxia
GeneticGenetic
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
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.
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseaseUbiquitin systemUbiquitin system
Freeubiquitin
Activatedubiquitin
Ubiquitinated protein
Damaged protein
proteosome
Degradedprotein
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseasePhysiological hypertrophyPhysiological hypertrophySkeletal muscle hypertrophy in response to exercise
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseasePathological hypertrophyPathological hypertrophyMyocardium in hypertensive heart disease
LV=left ventricle
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseasePathological hypertrophyPathological hypertrophyMyocardium in hypertensive heart disease
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseasePhysiological hyperplasiaPhysiological hyperplasiaEndometrium in the menstrual cycle
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseasePhysiological hyperplasiaPhysiological hyperplasia
Normal uterus
Pregnant uterus
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseasePathological hyperplasiaPathological hyperplasia
Normal skin Hyperplasia after trauma
RP = rete pegDP = dermal papilla
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseaseCommon causes of atrophyCommon causes of atrophy
DenervationDenervation ImmobilisationImmobilisation Reduced endocrine stimulationReduced endocrine stimulation IschaemiaIschaemia AgeingAgeing
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseasePathological atrophyPathological atrophy
A= atrophic skeletal muscle fibres
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in disease
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseaseApoptosisApoptosis
Normal cells are closely anchored by cell junctions
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseaseApoptosis: first stage...Apoptosis: first stage...
Cells lose contact and round up. There is nuclear condensation.
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseaseApoptosis next stage...Apoptosis next stage...
Apoptotic cell undergoes fragmentation to form apoptotic bodies
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseaseApoptosis final event...Apoptosis final event...
Apoptotic fragments are recognised by local cells and phagocytes, are internalised, and degraded.
Faculty of Medicine & Health Sciences, October 1999
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….
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
Cellular adaptations in diseaseExamples of metaplasiaExamples of metaplasia
Bladder transitional epithelium (T) with metaplasia to squamous epithelium (S) in response to a bladder stone…
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
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.
Faculty of Medicine & Health Sciences, October 1999
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
Faculty of Medicine & Health Sciences, October 1999
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.