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Cellular Adaptations in Disease Faculty of Medicine & Health Sciences Semester 3 Pathology Course P3 5th October 1999 Prof. James Lowe.

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Presentation on theme: "Cellular Adaptations in Disease Faculty of Medicine & Health Sciences Semester 3 Pathology Course P3 5th October 1999 Prof. James Lowe."— Presentation transcript:

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2 Cellular Adaptations in Disease Faculty of Medicine & Health Sciences Semester 3 Pathology Course P3 5th October 1999 Prof. James Lowe

3 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Overview Adaptability of cells to an altered environment Adaptability of cells to an altered environment Physiological and pathological stimuli Physiological and pathological stimuli Changes in growth pattern Changes in growth pattern Hyperplasia, hypertrophy, atrophy, involution, metaplasia Hyperplasia, hypertrophy, atrophy, involution, metaplasia Apoptosis Apoptosis Growth factors Growth factors Role in altered environment Role in altered environment

4 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Why is this important? Extremely common responses in disease Extremely common responses in disease Certain adaptations in growth act as a fertile ground for the later development of neoplasia - cancer formation… Certain adaptations in growth act as a fertile ground for the later development of neoplasia - cancer formation… Nomenclature is used in clinical work. Nomenclature is used in clinical work.

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6 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Adaptability of cells to an altered environment Cells are constantly exposed to changes in their environment Cells are constantly exposed to changes in their environment Cells can adapt to acceptable changes in their environment by modifying metabolism or growth pattern Cells can adapt to acceptable changes in their environment by modifying metabolism or growth pattern Environmental changes can be physiological or pathological Environmental changes can be physiological or pathological

7 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Examples of pathological stimuli Nutritional Nutritional Immune Immune Endocrine Endocrine Physical agents Physical agents Chemical agents Chemical agents Infections Infections Anoxia Anoxia Genetic Genetic

8 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Metabolic regulation Cells may adapt by metabolic regulation Cells may adapt by metabolic regulation Induction of enzyme Induction of enzyme Downregulation of enzyme Downregulation of enzyme Increased synthesis of product Increased synthesis of product Reduced secretion of product Reduced secretion of product Metabolic adaptation is usually not associated with morphological changes Metabolic adaptation is usually not associated with morphological changes

9 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Cell stress response The cell stress response allows cells to survive pathological stimuli The cell stress response allows cells to survive pathological stimuli Housekeeping genes switched off Housekeeping genes switched off Cell stress genes switched on Cell stress genes switched on Cells stress proteins are expressed in cells (also called heat shock proteins) Cells stress proteins are expressed in cells (also called heat shock proteins) Cell stress proteins are cytoprotective Cell stress proteins are cytoprotective

10 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Cell stress proteins Small cell stress proteins act as molecular chaperones and prevent misfolding of proteins Small cell stress proteins act as molecular chaperones and prevent misfolding of proteins Ubiquitin links to damaged proteins and flags them for elimination by the cell Ubiquitin links to damaged proteins and flags them for elimination by the cell Other groups of cell stress proteins have roles in the nucleus. Other groups of cell stress proteins have roles in the nucleus.

11 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Ubiquitin system Free ubiquitin Activated ubiquitin Ubiquitinated protein Damaged protein proteosome Degraded protein

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13 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Increased functional demand Increased functional demand can be met by two main responses Increased functional demand can be met by two main responses Increase in cell size: hypertrophy Increase in cell size: hypertrophy Increase in cell number: hyperplasia Increase in cell number: hyperplasia These may occur independently or together. These may occur independently or together. Reflected by an increase in size and weight of an organ Reflected by an increase in size and weight of an organ

14 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Physiological hypertrophy Skeletal muscle hypertrophy in response to exercise

15 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Pathological hypertrophy Myocardium in hypertensive heart disease LV=left ventricle

16 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Pathological hypertrophy Myocardium in hypertensive heart disease

17 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Physiological hyperplasia Endometrium in the menstrual cycle

18 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Physiological hyperplasia Normal uterus Pregnant uterus

19 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Pathological hyperplasia Normal skinHyperplasia after trauma RP = rete peg DP = dermal papilla

20 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Hyperplasia may be nodular Hyperplasia may occur in a non-uniform pattern in an organ or tissue - termed nodular hyperplasia Hyperplasia may occur in a non-uniform pattern in an organ or tissue - termed nodular hyperplasia Examples include Examples include hyperplasia of the prostate gland hyperplasia of the prostate gland hyperplasia of the breast hyperplasia of the breast

21 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Nodular hyperplasia of prostate From a young man showing uniform texture of gland From an elderly man showing irregular hyperplastic nodules. This would cause obstruction

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23 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Reduced demand for cell activity Reduction in the volume of a tissue is termed atrophy Reduction in the volume of a tissue is termed atrophy reduction in cell volume reduction in cell volume reduction in cell number reduction in cell number Cell loss is commonly replaced by either adipose tissue or fibrous tissue Cell loss is commonly replaced by either adipose tissue or fibrous tissue Refelected in a reduced size and mass of an organ Refelected in a reduced size and mass of an organ

24 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Common causes of atrophy Denervation Denervation Immobilisation Immobilisation Reduced endocrine stimulation Reduced endocrine stimulation Ischaemia Ischaemia Ageing Ageing

25 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Pathological atrophy A= atrophic skeletal muscle fibres

26 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Other causes of a small organ other than atrophy Hypoplasia: incomplete growth of an organ Hypoplasia: incomplete growth of an organ Agenesis: complete failure of development of an organ in embryogenesis Agenesis: complete failure of development of an organ in embryogenesis

27 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Physiological atrophy is termed involution Most instances of involution are the result of withdrawal of an endocrine stimulus Most instances of involution are the result of withdrawal of an endocrine stimulus Examples of involution Examples of involution breast after cessation of lactation breast after cessation of lactation uterus after parturition uterus after parturition thyroid after puberty thyroid after puberty

28 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Events in cell atrophy Cell components are removed by degradative systems Cell components are removed by degradative systems cytosolic proteolysis - ubiquitin system cytosolic proteolysis - ubiquitin system autophagy: elements enwrapped by internal membrane systems and fused with the lysosomal system autophagy: elements enwrapped by internal membrane systems and fused with the lysosomal system Residual lipid material may remain in cells as a brown material termed lipofuscin Residual lipid material may remain in cells as a brown material termed lipofuscin

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30 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Reduction in cell number is through programmed cell death Certain trophic signal to cells can lead to a specific form of cell death Certain trophic signal to cells can lead to a specific form of cell death Cell death is brought about by precise metabolic systems Cell death is brought about by precise metabolic systems The main type of programmed cell death is termed apoptosis The main type of programmed cell death is termed apoptosis

31 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Apoptosis Normal cells are closely anchored by cell junctions

32 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Apoptosis: first stage... Cells lose contact and round up. There is nuclear condensation.

33 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Apoptosis next stage... Apoptotic cell undergoes fragmentation to form apoptotic bodies

34 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Apoptosis final event... Apoptotic fragments are recognised by local cells and phagocytes, are internalised, and degraded.

35 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Apoptosis biology Cell death pathways exist in the cell metabolism controlled by the action of protease enzymes termed CASPASES Cell death pathways exist in the cell metabolism controlled by the action of protease enzymes termed CASPASES DNA is cleaved into fragments in between nuceosomes by endonucleases DNA is cleaved into fragments in between nuceosomes by endonucleases Protein in cells is cross linked by transglutaminases Protein in cells is cross linked by transglutaminases Cell death pathways can be triggered by several factors…. Cell death pathways can be triggered by several factors….

36 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Apoptosis triggers…. Surface receptor activation Surface receptor activation Surface membrane damage Surface membrane damage Damage to mitochondrial membranes Damage to mitochondrial membranes DNA damage DNA damage Whether a cell lives or dies depends on the balance between pro-apoptotic and anti- apoptotic factors

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38 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Change in cell differentiation Cells may respond to stimuli by a change in terminal differentiation Cells may respond to stimuli by a change in terminal differentiation This process is termed metaplasia This process is termed metaplasia

39 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Examples of metaplasia Bladder transitional epithelium (T) with metaplasia to squamous epithelium (S) in response to a bladder stone…

40 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Example of metaplasia Urothelium in response to stone Urothelium in response to stone transitional epithelium to squamous transitional epithelium to squamous Respiratory mucosa in response to smoking Respiratory mucosa in response to smoking Ciliated columnar epithelium to squamous Ciliated columnar epithelium to squamous Connective tissue in response to trauma Connective tissue in response to trauma Collagenous tissue to osseous tissue Collagenous tissue to osseous tissue

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42 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Growth factors Growth factors and their receptors control cell growth Growth factors and their receptors control cell growth In disease, cell adaptations are controlled by the action of growth factors linking to nuclear transcription factors via secondary messenger systems. In disease, cell adaptations are controlled by the action of growth factors linking to nuclear transcription factors via secondary messenger systems.

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44 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Summary Cells adapt to altered environment Cells adapt to altered environment Metabolic adaptation Metabolic adaptation Cell stress response Cell stress response Changes in growth pattern Changes in growth pattern Hyperplasia, hypertrophy, atrophy, involution, metaplasia Hyperplasia, hypertrophy, atrophy, involution, metaplasia Growth factors, controlling proliferation or cell death, play a key role in cell adaptations in disease Growth factors, controlling proliferation or cell death, play a key role in cell adaptations in disease

45 Faculty of Medicine & Health Sciences, October 1999 Cellular adaptations in disease Links to future work... Cell biology of apoptosis will be continued when we consider neoplasia and in MM course Cell biology of apoptosis will be continued when we consider neoplasia and in MM course Cell biology of growth factors will be continued when we consider healing and repair and will also crop up in study of neoplasia. Cell biology of growth factors will be continued when we consider healing and repair and will also crop up in study of neoplasia.


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