Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Cell injuryadaptation 2

593 views

Published on

for Undergraduate medical students (MBBS)

Published in: Health & Medicine
  • Be the first to comment

Cell injuryadaptation 2

  1. 1. Cell Injury and Adaptations -2Cell Injury and Adaptations -2 Dr.CSBR.Prasad, M.D.
  2. 2. AtrophyAtrophy
  3. 3. Cell number Cell size Cell substance Organ / tissue size
  4. 4. AtrophyAtrophy Def: Shrinkage in the size of the cell by the loss of cell substance As a result organ / tissue size diminishes Ex: Skeletal muscle in disuse Ischemia causing reduction in size of a limb
  5. 5. AtrophyAtrophy Because of atrophy of cells, organ / tissue size diminishes Atrophic cells have diminished function but they are not dead There may be over all loss of number of cells in an organ It’s a retreat for the cells to a smaller size at which survival is still possible
  6. 6. AtrophyAtrophy Causes:Causes: 1. < work load 2. < blood supply 3. Inadequate nutrition 4. Loss of endocrine stimulation 5. Aging
  7. 7. AtrophyAtrophy Mechanism:Mechanism: Regulation of protein degradation play a key role in atrophy There are two proteolytic systemsThere are two proteolytic systems involved in degradationinvolved in degradation 1. Lysosomes 2. Ubiquitin-proteasome pathway
  8. 8. AtrophyAtrophy Microscopic changes:Microscopic changes: 1. Decrease in size of the cell 2. Marked increase in number of autophagic vacuoles 3. Lipofuchsin accumulation
  9. 9. AtrophyAtrophy
  10. 10. AtrophyAtrophy
  11. 11. Cancer cachexia:Cancer cachexia: Proteasome pathway is activated in hypercatabolic state including cancer cachexia
  12. 12. Lipofuscin granules in a cardiac myocyteLipofuscin granules in a cardiac myocyte
  13. 13. HypertrophyHypertrophy
  14. 14. Cell number Cell size Cell substance Organ / tissue size
  15. 15. HypertrophyHypertrophy • Increase in size of the cells • Increase in organ size and tissue size • NO NEW CELLSNO NEW CELLS
  16. 16. HypertrophyHypertrophy Causes: • Increased functional demandIncreased functional demand • Specific hormonal stimulusSpecific hormonal stimulus
  17. 17. HypertrophyHypertrophy Basic Mechanisms: 1.1. Increased synthesis of structural proteinsIncreased synthesis of structural proteins / organelle/ organelle 2.2. Increased DNA contentIncreased DNA content 3.3. Rarely - a change in cellular phenotypeRarely - a change in cellular phenotype
  18. 18. Mechanisms of myocardial hypertrophy
  19. 19. HypertrophyHypertrophy Types: 1.1. PhysiologicalPhysiological 2.2. PathologicalPathological
  20. 20. HypertrophyHypertrophy Types:Types: 1-Physiological1-Physiological Eg:Eg: - Uterus during pregnancy- Uterus during pregnancy - Exercise induced increase in muscle bulk- Exercise induced increase in muscle bulk 2-Pathological2-Pathological Eg:Eg: - Concentric hypertrophy of LV in HTN / AS / AR- Concentric hypertrophy of LV in HTN / AS / AR - Hypertrophy of residual cardiac myocytes after MI- Hypertrophy of residual cardiac myocytes after MI - Hypertrophy of smooth muscle in the intestinal wall proximal- Hypertrophy of smooth muscle in the intestinal wall proximal to obstructionto obstruction Note:Note: some times hypertrophy and hyperplasia may occursome times hypertrophy and hyperplasia may occur togethertogether eg: uterus in pregnancyeg: uterus in pregnancy
  21. 21. HypertrophyHypertrophy Whatever the mechanism, after a stage,Whatever the mechanism, after a stage, degenerative changes take placedegenerative changes take place Eg: fragmentation and loss of myofilamentary contractile protein This may be due to increased demand for blood supply which is finite
  22. 22. HypertrophyHypertrophy
  23. 23. Physiologic hypertrophy ofPhysiologic hypertrophy of the uterus during pregnancythe uterus during pregnancy
  24. 24. Sturge-Weber syndrome
  25. 25. HyperplasiaHyperplasia
  26. 26. Cell number Cell size Cell substance Organ / tissue size
  27. 27. HyperplasiaHyperplasia • Increase in number of cells • Increase in organ size and tissue size • NEW CELLS will formNEW CELLS will form • New cell form from stem cells / resting cell
  28. 28. HyperplasiaHyperplasia Types:Types: • Physiological 1.1. HormonalHormonal eg: EM, Breast, Uterus in pregnancy 2.2. CompensatoryCompensatory eg: Partial hepatectomy, wound healing • Pathological EM hyperplasias, adrenal cortical hyperplasia due to pituitary tumor; TSH secreting adenoma of pituitary, Stimulatory Ig against TSH receptor---> thyroid hyperplasia; Androgens & prostate
  29. 29. HyperplasiaHyperplasia Pathological - Mostly due to excessive hormone stimulation or growth factor stimulation eg: EM proliferation - Increased sensitivity to growth factors eg: HPV infection of skin Note: pathological hyperplasias constitute a fertile soil for possible future cancer Eg: EM hyperplasia HPV infection and cervical cancer
  30. 30. HyperplasiaHyperplasia Main difference between hyperplasia andMain difference between hyperplasia and cancers:cancers: In Hyperplasia : proliferation is controlled In Cancers : proliferation is uncontrolled
  31. 31. ClinicalClinical ApplicationsApplications
  32. 32. 1 - In a patient with bleeding PV, US1 - In a patient with bleeding PV, US showed endometrial hyperplasia.showed endometrial hyperplasia. • What do you elicit in history? • Assume that this patient had an ovarian tumor. Can you guess what is the nature of tumor? Collaterals: • What do you call such tumors? Can you give some more examples? • Unfortunately, endometrial biopsy turned out to be endometrial carcinoma. Surgeon considered oophorectomy as a part of treatment. What is your comment?
  33. 33. 2 - Earlier breast carcinomas were2 - Earlier breast carcinomas were treated by mastectomy andtreated by mastectomy and oophorectomy and adrenalectomy.oophorectomy and adrenalectomy. • How oophorectomy will benefit the patient?
  34. 34. MetaplasiaMetaplasia
  35. 35. MetaplasiaMetaplasia Def: one adult cell type is replaced by another adult cell type It’s a reversiblereversible change It may involve epitheliumepithelium or mesenchymalmesenchymal tissue
  36. 36. MetaplasiaMetaplasia Preference to the fittest for a given injury
  37. 37. MetaplasiaMetaplasia Mechanism:Mechanism: Arises from genetic reprogramming of epithelial stem cells or of undifferentiated mesenchymal cells
  38. 38. MetaplasiaMetaplasia Examples:Examples: Smoking : squamous metaplasia of respiratory epithelium Vit-A deficiency: squamous metaplasia of respiratory epithelium Chronic cervical infections: squamous metaplasia of endocervical epithelium Urinary stones: squamous metaplasia of urothelium GERD: gatric / intestinal metaplasia in squamous epithelium of esophagus Gastritis: Mucous metaplasia in gastric epithelium
  39. 39. MetaplasiaMetaplasia Also occur in mesenchymal tissue BUT - It’s not an adaptive response Examples:Examples: - bone & cartilage formation in soft tissues after an injury - tumor metaplasias
  40. 40. MetaplasiaMetaplasia Consequences:Consequences: 1. Loss of protective mechanism 2. Fertile soil for cancers
  41. 41. Metaplasia in esophagusMetaplasia in esophagus
  42. 42. DysplasiaDysplasia
  43. 43. Intracellular accumulationsIntracellular accumulations
  44. 44. Intracellular accumulationsIntracellular accumulations Accumulation of abnormal amounts of various substances Three categories:Three categories: 1- Normal cellular constituents accumulated in excess eg: H2O, Lipid, Proteins, CHO 2- Accumulation of abnormal substance Exogenous eg: minerals, infectious agents Endogenous eg: abnormal synthesis, abnormal metabolism 3- Pigment
  45. 45. Intracellular accumulationsIntracellular accumulations Substances accumulated:Substances accumulated: 1. Transient accumulations 2. Permanent accumulations • Harmless • Toxic 1. Cytoplasm 2. Nucleus
  46. 46. Intracellular accumulationsIntracellular accumulations Processes that result in intracellular accumulations:Processes that result in intracellular accumulations: 1. Normal endogenous product at the normal rate / induced rate but with reduced rate of removal 2. Normal / abnormal endogenous products accumulate bec’ of defective metabolism (packge/transport/secretion). It’s usually a gentic defect 3. Accumulation of abnormal exogenous substance bec’ cell has no machinary to degrade or export to other sites
  47. 47. Intracellular accumulationsIntracellular accumulations If Overload is due toIf Overload is due to: Systemic derangementsSystemic derangements: reversible Genetic defectGenetic defect: irreversible - progressive
  48. 48. Intracellular accumulationsIntracellular accumulations Accumulation of LIPIDSAccumulation of LIPIDS: Any class of lipids may get accumulatedAny class of lipids may get accumulated TriglyceridesTriglycerides Cholesterol / cholesterol esterCholesterol / cholesterol ester PhospholipidsPhospholipids Complex of lipids & carbohydratesComplex of lipids & carbohydrates (Eg: Lysosomal storage diseases)(Eg: Lysosomal storage diseases)
  49. 49. Intracellular accumulationsIntracellular accumulations FATTY CHANGE: (STEATOSIS)FATTY CHANGE: (STEATOSIS) Accumulation of triglyceridesAccumulation of triglycerides Usually seen inUsually seen in liverliver (can also occur in kidney, heart, skeletal(can also occur in kidney, heart, skeletal muscle)muscle)
  50. 50. Intracellular accumulationsIntracellular accumulations FATTY CHANGE: (STEATOSIS)FATTY CHANGE: (STEATOSIS) Causes:Causes: ToxinsToxins AlcoholAlcohol PEMPEM DMDM ObesityObesity AnoxiaAnoxia
  51. 51. Intracellular accumulationsIntracellular accumulations FATTY CHANGE:FATTY CHANGE: LiverLiver Significance:Significance: depends on thedepends on the  CauseCause  Severity of accumulationSeverity of accumulation  NASHNASH (may lead to cirrhosis, HCC)(may lead to cirrhosis, HCC)
  52. 52. Intracellular accumulationsIntracellular accumulations FATTY CHANGE:FATTY CHANGE: LiverLiver Morphology:Morphology: Uniform enlargementUniform enlargement Yellowish with greater accumulation of fatYellowish with greater accumulation of fat Borders are sharpBorders are sharp Capsule is stretchedCapsule is stretched c/s greasyc/s greasy
  53. 53. Intracellular accumulationsIntracellular accumulations FATTY CHANGE:FATTY CHANGE: LiverLiver Microscopy:Microscopy: Minute membrane bound vesiclesMinute membrane bound vesicles First seen around the nucleusFirst seen around the nucleus With progressive accumulation cellsWith progressive accumulation cells resembles adipocyteresembles adipocyte Fatty cystsFatty cysts
  54. 54. Intracellular accumulationsIntracellular accumulations FATTY CHANGE:FATTY CHANGE: HeartHeart Gross:Gross: Two patterns of accumulationsTwo patterns of accumulations Tigroid effect (hypoxia)Tigroid effect (hypoxia) alternating layers of brown and yellowalternating layers of brown and yellow Yellow heart (Diphtheria, severe hypoxia)Yellow heart (Diphtheria, severe hypoxia) Diffuse accumulation in almost all cellsDiffuse accumulation in almost all cells
  55. 55. Intracellular accumulationsIntracellular accumulations FATTY CHANGE:FATTY CHANGE: HeartHeart Microscopy:Microscopy: Small clear vaucoles in the cardiacSmall clear vaucoles in the cardiac myocytesmyocytes
  56. 56. Intracellular accumulationsIntracellular accumulations FATTY CHANGE:FATTY CHANGE: DDDD Intracellular accumulations ofIntracellular accumulations of fatfat,, glycogenglycogen andand waterwater cannot be differentiated bycannot be differentiated by routine histologyroutine histology Special stains are needed forSpecial stains are needed for differentiationdifferentiation
  57. 57. Intracellular accumulationsIntracellular accumulations FATTY CHANGE:FATTY CHANGE: DDDD Special stains that will help to differentiate fat andSpecial stains that will help to differentiate fat and glycogenglycogen Sudan III / IVSudan III / IV fat – red / orangefat – red / orange Sudan blackSudan black fat – blackfat – black Oil Red – OOil Red – O fat – red / orangefat – red / orange Nile blue ANile blue A fat – redfat – red PASPAS stains glycogen (pink)stains glycogen (pink) NoteNote:: for the demonstration of fatfor the demonstration of fat frozen sections are used.frozen sections are used.
  58. 58. Atherosclerosis, Oil red - O
  59. 59. Intracellular accumulationsIntracellular accumulations Cholesterol / cholestryl ester:Cholesterol / cholestryl ester: Every cell uses choleterol for the synthesis of itsEvery cell uses choleterol for the synthesis of its cell membranecell membrane Accumulation of cholesterol is alwaysAccumulation of cholesterol is always pathologicalpathological Conditions:Conditions: CholesterolosisCholesterolosis ASAS XanthomasXanthomas Inflammation / necrosisInflammation / necrosis Niemann – Pick disease type-CNiemann – Pick disease type-C
  60. 60. Intracellular accumulationsIntracellular accumulations Atherosclerosis:Atherosclerosis: Seen in large and medium sized arteriesSeen in large and medium sized arteries MØ smooth muscle cells accumulate withMØ smooth muscle cells accumulate with in the intimal layerin the intimal layer They are filled with lipid vacuoles – FoamThey are filled with lipid vacuoles – Foam cellscells GrossGross: produces yellow plaques: produces yellow plaques Cholesterol clefts may be seenCholesterol clefts may be seen
  61. 61. Fatty streaks
  62. 62. Fatty streaks
  63. 63. Varying grades of AS
  64. 64. AS involving coronary artery – cholesterol clefts
  65. 65. AS involving coronary artery – Foamy macrophages, cholesterol clefts
  66. 66. Cholesterol clefts
  67. 67. Intracellular accumulationsIntracellular accumulations Xanthomas:Xanthomas: Intracellular accumulation of fat in MØIntracellular accumulation of fat in MØ Some hereditary hyperlipidemiasSome hereditary hyperlipidemias Foam cells are seen in the subepithelialFoam cells are seen in the subepithelial connective tissueconnective tissue Clinically they produce tumorsClinically they produce tumors
  68. 68. Intracellular accumulationsIntracellular accumulations Inflammation / necrosis:Inflammation / necrosis: foamy MØ are seen at these sitesfoamy MØ are seen at these sites When they are in excessive number theyWhen they are in excessive number they produce yellowish colour to the siteproduce yellowish colour to the site Eg:Eg: Xanthogranulomatous pyelonphritisXanthogranulomatous pyelonphritis xanthogranulomasxanthogranulomas
  69. 69. Xanthogranulomatous pyelonephritis
  70. 70. Intracellular accumulationsIntracellular accumulations Cholesterolosis:Cholesterolosis: Focal accumulations of foamy MØ in theFocal accumulations of foamy MØ in the lamina propria of gall bladderlamina propria of gall bladder
  71. 71. Cholesterolosis of Gall Bladder
  72. 72. Tendinous xanthomas
  73. 73. Erruptive xanthomas
  74. 74. Xanthelasma
  75. 75. Mucopolysaccharidoses - 1
  76. 76. Niemann-Pick Disease
  77. 77. Niemann-Pick Disease
  78. 78. Waterhouse-Friderichsen Syndrome
  79. 79. Wegener’s granulomatosis
  80. 80. E N D

×