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L1-Cell injuiry -Lecture of Pathology.pptx
- 1. LECTURE TITLE: CELL INJURY Lecturername: Dr. Maha Arafah Lecture Date: 15-9-2012 (Foundation Block, pathology)
- 2. CONCEPT OF INJURYAND CELLULAR RESPONSE TO INJURY L1: Overview of Cell Injury, adaptation to environmental stress and Cell Death Free radical injury, types of necrosis and apoptosis L2: Mechanism of injury, Necrosis and Apoptosis Cellular accumulation and adaptation to injuries L3: Cellular accumulation and Calcification Pathological calcification
- 3. OVERVIEW OF CELLINJURY AND ADAPTATION Upon completion of this lecture, the student should know: • Causes of cell injury • Adaptation to stress •Reversible cell injury ( nonlethal hit) • Irreversible injury and cell death ( lethal hit) • Morphology of cell injury
- 4. CONCEPT OF INJURYAND CELLULAR RESPONSE TO INJURY Cells are constantly exposed to a variety of stresses. When too severe, INJURY results. Injury alters the preceding normal steady state of the cell.
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- 12. Cellular Responses toInjury Nature and Severity of Injurious Stimulus Cellular Response Altered physiologic stimuli: Cellular adaptations: Increased demand, increased trophic stimulation (e.g. growth factors, hormones) Hyperplasia, hypertrophy Decreased nutrients, stimulation Atrophy Chronic irritation (chemical or physical) Metaplasia
- 13. The Four MainTypes of Cell Adaptations Atrophy: shrinkage of an organ as a result of decreased cell size (and cell number). Hypertrophy: enlargement of an organ as a result of increased cell size. Hyperplasia: enlargement of an organ through an increase in cell number. Metaplasia: the replacement of one differentiated cell type by another in a tissue or organ.
- 14. Atrophy Reversible Decrease in sizeof cell (-s) previously of normal size Physiologic shrinkage of testes and ovaries with age Pathologic • Decreased function • Loss of innervation • Pressure (“bed soars”) • Malnutrition/cahexia • Loss of endocrine stimulation • Aging Net results: tissue /organ smaller than normal Signals/injury Atrophy Hypoplasia & Aplasia • Developmental failure • Failure in morphogenesis Autophagy Less organells Reduced metabolic rate Lipofuscin granules
- 15. LIPOFUSCIN: wear andtear pigment Lipofuscin granules are yellow/brown in color and represent non-digestible fragments of lipids and phospholipids combined with protein within autophagic vacuoles. They are commonly seen in ageing liver and myocardial cells.
- 16. Hypertrophy – cellor organ Reversible Increase in size of cell in response to increased functional demand and/or in response to Hormone/growth factors stimulation Physiologic • Athletes muscle • Pregnant uterus • Prostatic tissue (elderly) Pathologic • Cardiac muscle • bladder smooth muscle hypertrophy in outflow obstruction Net effect: increase in size/volume/weight of tissue / organ Signals/injury Occur in cells which cannot divid
- 17. Morphology of hypertrophy Hypertrophic muscle cells show: Increased membrane synthesis. Increased amounts of ATP. Increased enzyme activity. Increased myofilaments. Hypertrophy of smooth endoplasmic reticulum
- 18. 18 Hyperplasia – cellor organ Reversible Increase in number of cells in response to increased functional demand and/or in response to Hormone/Growth Factor stimulation Physiologic • Uterine muscle in pregnancy • Lactating breast • Compensatory after hepatectomy Pathologic • Endocrine stimulation, e.g. Thyroid • Focal nodular hyperplasia (liver) • Adenomatous hyperplasia of endometrium Net effect :increase in size/volume/weight of tissue / organ Signals/injury
- 20. 20 Endometrial hyperplasia Endometrial carcinomaendometrial hyperplasia Can be transformed to endometrial carcinoma
- 21. Signals/injury Reversible But not always Metaplasia Substitutionof mature (differentiated) cell for another mature cell Physiologic (metaplastic tissue/organs) • cervical canal Pathologic (metaplastic tissue/organs) • Gastric/duodenal metaplasia • Ciliated to squamous in bronchial epith. • Osseous metaplasia • Barret’s oesophagus Net effect: another cell/tissue - protective – changes in function genetic "reprogramming" of stem cells
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- 23. Notice Metaplasia isoften seen next to neoplastic epithelium, indicating that although this adaptive response is potentially reversible, continued insult to the cells may cause uncontrolled growth and the development of cancer.
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- 26. Causes of cellinjury 1. DEFICIENCY OF OXYGEN Ischemia vs. Hypoxia 2. PHYSICAL AGENTS 3. CHEMICAL AGENTS 4. INFECTION 5. IMUNOLOGICAL REACTIONS 6. GENETIC DERANGEMENTS 7. NUTRITIONAL IMBALANCE 8. AGING
- 27. Brain – massivehaemorrhagic focus (ischemia) in the cortex This is a lesion caused by DEFICIENCY OF OXYGEN
- 28. Abscess of thebrain (bacterial) This is a lesion caused by infectious agent
- 29. This is alesion caused by chemical agent Hepatic necrosis (patient poisoned by carbon tetrachloride)
- 30. Pulmonary caseous necrosis(coccidioidomycosis) This is a lesion caused by infectious agent
- 31. Gangrenous necrosis offingers secondary to freezing This is a lesion caused by physical agent
- 32. The “boutonnière” (buttonhole)deformity This is a lesion caused by intrinsic factors (autoimmune disease)
- 33. Liver: macronudular cirrhosis(HBV) This is a lesion caused by infectious agent: Viral hepatitis (chemical:alcohol, genetic:a1-AT deficiency)
- 34. MORPHOLOGY OF CELLS INREVERSIBLE AND IRREVERSIBLE INJURY
- 35. myocadial cells: lossof function after 1-2 min of ischemia However do not die until 20 to 30 min of ischemia EM: 2-3 hours, LM 6-12 hours
- 37. Morphologic changes inReversible Injury Early changes: (1) Cloudy swelling or hydropic changes: Cytoplasmic swelling and vacuolar degeneration due to intracellular accumulation of water and electrolytes secondary to failure of energy-dependent sodium pump. 2) Mitochondrial and endoplasmic reticulum swelling due to loss of osmotic regulation. 3) Clumping of nuclear chromatin.
- 39. Vacuolar (hydropic) changein cells lining the proximal tubules of the kidney Reversible changes
- 40. Morphologic changes inirreversible injury: 1. Severe vacuolization of the mitochondria, with accumulation of calcium-rich densities. 2. Extensive damage to plasma membranes. 3. Massive calcium influx activate phospholipase, proteases, ATPase and endonucleases with break down of cell component. 4. Leak of proteins, ribonucleic acid and metabolite. 5. Breakdown of lysosomes with autolysis. 6. Nuclear changes: Pyknosis, karyolysis, karyorrhexis.
- 42. IRREVERSIBLE CELL INJURY-NECROSIS
- 45. Morphologic changes inirreversible injury - Dead cell are either collapsed and form a whorled phospholipid masses or degraded into fatty acid with calcification. - Cellular enzymes are released into circula- tion. This provides important clinical parameter of cell death e.g. increased level of creatinin kinase in blood after myocardial infarction
- 46. Myocardial infarct Thisis a lesion caused by oxygen deprivation Cell Pathology
- 47. MECHANISMS OF CELLINJURY General principles: - The cellular response to injurious stimuli depends on 1. type of injury 2. Its duration 3. Severity -The consequences depend on the type, status, adaptability, and genetic makeup of the injured cell. -The structural and biochemical components of a cell are so integrally connected that multiple secondary effects rapidly occur -Cellular function is lost far before cell death occurs
- 48. TAKE HOME MESSAGES: Cell injury is common event and the body respond by adaptation to a certain limit. Adaptation include atrophy, hypertrophy, hyperplasia and metaplasia. Cellular injury is caused by various elements include bacterial toxins, hypoxia, alcohol, viruses and radiation. Cellular injury could be reversible (sublethal) or irreversible (lethal).
- 49. Dr. Maha Arafah 15-9-2011 (FoundationBlock, pathology) THANK YOU