Cell injuryadaptation 1
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Cell injuryadaptation 1
- 1. Cell injuryCell injury && Adaptation -1Adaptation -1 Dr.CSBR.Prasad, M.D. CSBRP-V3-Dec-2011
- 2. Case-1 • A 45 yo male with a chronic smoking history suddenly developed chest pain after a meal. • Pain was retrosternal and radiating to left arm along the ulnar to the tip of left little finger • After 6 hours of travelling he reached a cardiac care center where Chest x-ray, ECG and some blood tests were done CSBRP-V3-Dec-2011
- 3. Case-2 • 25yo male developed fever associated with jaundice • He had a tender hepatomegaly • Serum bilirubin was 7.0mg/dl • Liver enzymes are enormously elevated CSBRP-V3-Dec-2011
- 4. Divisions in the study of Pathology • General pathology • Systemic pathology Basic reactions of cells and tissues to abnormal stimuli that underlie all diseases Specific responses of specialized organs and tissues to stimuli CSBRP-V3-Dec-2011
- 5. The four aspects of disease process 1. Etiology (cause) 2. Pathogenesis (mechanism of disease) 3. Morphological changes (structural alterations) 4. Functional consequences (clinical significance) CSBRP-V3-Dec-2011
- 6. Rudolf Virchow [Father of Modern Pathology] ““Virtually all forms ofVirtually all forms of tissue injury starts withtissue injury starts with molecular or structuralmolecular or structural alterations in CELLS”alterations in CELLS” CSBRP-V3-Dec-2011
- 7. Subcellular compartments:Subcellular compartments: 1. Nucleus 2. Mitochondria 3. ER 4. Golgi apparatus 5. Lysosomes 6. Cytosol CSBRP-V3-Dec-2011
- 10. HomeostasisHomeostasis When the cell is functioning properly it’s said to be in a “steady statesteady state” i.e. it can handle normal physiological demands CSBRP-V3-Dec-2011
- 11. TermsTerms • Cell injuryCell injury • AdaptationsAdaptations CSBRP-V3-Dec-2011
- 12. Cell injuryCell injury • Reversible injuryReversible injury 1-Cell swelling 2-Fatty change 3-Mitochondrial swelling 4-ER disruption 5-Membrane blebs 6-Cytoskeleton disruption • Irreversible injuryIrreversible injury 1-Apoptosis 2-Necrosis CSBRP-V3-Dec-2011
- 15. Causes of injuryCauses of injury 1. Ischemia / hypoxia 2. Physical agents 3. Chemical agents 4. Infections 5. Immune reactions 6. Gene defects 7. Nutritional imbalances CSBRP-V3-Dec-2011
- 17. Ischemic & Hypoxic injuryIschemic & Hypoxic injury CSBRP-V3-Dec-2011
- 18. ISCHEMIAISCHEMIA HYPOXIAHYPOXIA Blood flowBlood flow Decreased due toDecreased due to vascular occlusionvascular occlusion Flow is normalFlow is normal OO22 tensiontension NormalNormal LowLow Delivery ofDelivery of substratessubstrates DecreasedDecreased NormalNormal Anerobic glycolysisAnerobic glycolysis Ceases faster as there isCeases faster as there is no substrate deliveryno substrate delivery Continues for a muchContinues for a much more longer timemore longer time Tissue injuryTissue injury Occurs with in a shortOccurs with in a short timetime Takes longer timeTakes longer time Note:Note: Ischemia injures tissues faster than hypoxia.Ischemia injures tissues faster than hypoxia. Differences between Ischemic and Hypoxic injuryDifferences between Ischemic and Hypoxic injury CSBRP-V3-Dec-2011
- 19. Ischemic & Hypoxic injuryIschemic & Hypoxic injury Decreased oxidative phosphorylation inDecreased oxidative phosphorylation in mitochondria [mitochondria [effecteffect: low ATP levels]: low ATP levels] Effects of Low ATP levels:Effects of Low ATP levels: 1.< activity of Na+ pump [Link] 2.> glycolysis (< intracellular glycogen) 3.Lowered intracellular pH (acidosis) 4.Detachment of ribosomes (< protein synthesis) DD Ischemia / Hypoxia CSBRP-V3-Dec-2011
- 23. IschemiaIschemia // Reperfusion injuryReperfusion injury • It represents exaggerated / acceleratedexaggerated / accelerated injuryinjury that occurs when blood flow is restored contrary to the expectation of recovery • It’s seen especially in myocardium and brain CSBRP-V3-Dec-2011
- 24. IschemiaIschemia // Reperfusion injuryReperfusion injury MechanismsMechanisms: • Reperfusion results in high concentration of Ca+ in the environment which cannot be handled by the injured cell • Reperfusion results in augmented recruitment of inflammatory cells to the injured area with resultant >levels of reactive oxygen species • Antioxidant defence mechanisms are not well restored CSBRP-V3-Dec-2011
- 25. Free radical – induced cell injuryFree radical – induced cell injury CSBRP-V3-Dec-2011
- 26. Free radical – induced cell injuryFree radical – induced cell injury What are free radicals?What are free radicals? • They are a chemical species with a single unpaired electron in an outer orbital • They are extremely unstable • They readily react with organic & inorganic chemicals • With in the cell they attack – Nucleic acids – Membrane molecules • They are autocatalytic CSBRP-V3-Dec-2011
- 27. Free radical – induced cell injuryFree radical – induced cell injury • Injury by activated oxygen species • Free radical injury underlies 1. Chemical 2. Radiation 3. Toxicity from oxygen 4. Cellular aging 5. Microbial killing by phagocytes 6. Inflammatory cell damage 7. Tumor destruction by MØ CSBRP-V3-Dec-2011
- 28. NOTE: Production of free radicals in the cell:Production of free radicals in the cell: 1. due to insults (ex: chemical, radiation) 2. as a part of normal cellular activities CSBRP-V3-Dec-2011
- 29. Free radical – induced cell injuryFree radical – induced cell injury How they are produced with in the cells?How they are produced with in the cells? They are by products of normal cellThey are by products of normal cell metabolismmetabolism 1. Redox reactions [link] 2. Nitric oxide 3. Ionizing radiation 4. Enzymatic metabolism of some exogenous chemicals (ex: CCl4) CSBRP-V3-Dec-2011
- 30. Free radical – induced cell injuryFree radical – induced cell injury Important reactions that mediate cellImportant reactions that mediate cell injury by free radicals:injury by free radicals: • Lipid peroxidation of membranesLipid peroxidation of membranes • DNA fragmentationDNA fragmentation • Cross-linking of proteinsCross-linking of proteins CSBRP-V3-Dec-2011
- 33. NOTE: Production of free radicals in the cell:Production of free radicals in the cell: 1. due to insults (ex: chemical, radiation) 2. as a part of normal cellular activities There are many intracellular mechanismsThere are many intracellular mechanisms that neutralize the normally produced freethat neutralize the normally produced free radicalsradicals CSBRP-V3-Dec-2011
- 34. Mechanisms to neutralize free radicalsMechanisms to neutralize free radicals produced normally with in the cells:produced normally with in the cells: • SODs • GSH / GSSH • Catalase • Anti-oxidants (Endogenous or exogenous) • Sequestration into other proteins CSBRP-V3-Dec-2011
- 35. Free radical – induced cell injuryFree radical – induced cell injury Natural NeutralizersNatural Neutralizers Superoxide radical O2 Hydrogen peroxide H2O2 OH SOD Catalase GSH/GSSH CSBRP-V3-Dec-2011
- 38. Chemicals induce injury by any one of the two mechanisms: 1. Direct action (unaltered chemical) 2. Indirect action (altered chemical) Chemical injuryChemical injury CSBRP-V3-Dec-2011
- 39. 1. Direct action (unaltered chemical): They combine with a critical molecular component or cellular organelle Ex: HgCl2 (binding with –SH groups of various cell membrane proteins) Other examples: anti-neoplastic drugs antibiotics Chemical injuryChemical injury CSBRP-V3-Dec-2011
- 40. 1. Direct action (unaltered chemical): “The greatest damage occurs to those cells that use, absorb, excrete or concentrate the compound” Chemical injuryChemical injury CSBRP-V3-Dec-2011
- 41. 2. Indirect action (altered chemical): They are converted toxic metabolites Conversion occurs in the P450 of SER of liver Mechanism of injury: a- formation of reactive free radicals b- direct covalent binding to protein & lipids Ex: CCl4 and Acetaminophen Chemical injuryChemical injury CSBRP-V3-Dec-2011
- 42. 2. Indirect action (altered chemical): Action of CCl4 It’s converted in to toxic free radical CCl3 Cause lipid peroxidation, break down of ER In <30 min hepatic synthesis of proteins drops and in 2hrs swelling of SER and dissociation of ribosomes Fatty liver Mitochondrial injury – drop in ATP – cell swelling At the end Ca+ influx – activation of enzymes – cell death Chemical injuryChemical injury CSBRP-V3-Dec-2011
- 43. The answer is “No”“No” Injury of limited severity and short duration allows the cells to come back to their normal functional levels Survival of the cell to injury depends on its ability to respond and adapt to injury Are all injurious stimuli lethal?Are all injurious stimuli lethal? CSBRP-V3-Dec-2011
- 46. This is normal liver at medium power with zone 1 in periportal region, zone 2 in the middle of the lobule, and zone 3 in centrilobular region. A central vein and a portal triad define the lobule. CSBRP-V3-Dec-2011
- 52. More examplesMore examples 1. Saccharin induced bladder cancer 2. Benzidine induced bladder cancer 3. Tx hyperthyroidism with radioactive iodine. 4. Anemia and DM 5. Hypoxic brain damage in severe anemia 6. Cystein given before radiation treatment for cancers 7. Antioxidants and longivityCSBRP-V3-Dec-2011
- 53. Which cell in the body thatWhich cell in the body that runs by anerobic glycolysisruns by anerobic glycolysis NORMALLY?NORMALLY? CSBRP-V3-Dec-2011
- 54. Response to injuryResponse to injury Depends on:Depends on: • Type of injury • Duration • Severity / extent • Consequences depend on 1. cell type 2. pre-existing state 3. adaptive response CSBRP-V3-Dec-2011
- 55. Response to injuryResponse to injury Can be:Can be: 1. Recovery 2. Adaptation 3. Apoptosis 4. Necrosis CSBRP-V3-Dec-2011
- 56. Adaptation:Adaptation: Alterations in cellular function / morphology to survive the insult Response to injuryResponse to injury CSBRP-V3-Dec-2011
- 57. AdaptationAdaptation Can be seen in twotwo situations: 1.1. PhysiologicalPhysiological adaptation 2.2. PathologicalPathological adaptation CSBRP-V3-Dec-2011
- 58. AdaptationAdaptation PhysiologicalPhysiological Adaptation to demand Ex:Ex: Enlargement of breast during puberty Enlargement of uterus during pregnancy Enlargement of biceps in iron pumpers PathologicalPathological Adaptation to injury in order to withstand the insult Ex:Ex: Wasting of muscle due to ischemia / disuse Increase in thickness of LV in HTN Osteopenia in bed ridden patients CSBRP-V3-Dec-2011
- 59. Cell adaptation to stressCell adaptation to stress Types of adaptations:Types of adaptations: 1. Hyperplasia 2. Hypertrophy 3. Atrophy 4. Metaplasia CSBRP-V3-Dec-2011
- 60. Cell adaptation to stressCell adaptation to stress Molecular mechanisms:Molecular mechanisms: Changes can occur at different levels 1. Receptors 2. Protein transcription 3. Switch of protein synthesis from one type to other CSBRP-V3-Dec-2011
- 61. HyperplasiaHyperplasia • Increase in the number of cells in an organ or tissue • Hence there is increase in volume of the organ or tissue • There is increased mitotic activity – >DNA synthesis • Usually it occurs with hypertrophy • Triggered by external stimuli • Hyperplasia can be physiological or pathological Ex: hormone induced growth of uterus CSBRP-V3-Dec-2011
- 62. Hyperplasia (HP)Hyperplasia (HP) • Physiological hyperplasia divided into 1-Hormonal HP 2-Compensatory HP 1-Hormonal HP: increases the functional capacity of the tissue Ex: Proliferation of glandular epithelium in breast at puberty, pregnancy Proliferation of smooth muscle of gravid uterus 2-Compensatory HP: increases tissue mass after damage / partial resection Ex: Capacity of the liver to regenerate unilateral nephrectomy with compensatory hyperplasia of contralateral kidney CSBRP-V3-Dec-2011
- 63. Prometheus chained to a mountain
- 65. Pathological hyperplasiaPathological hyperplasia • Due to the action of GF or excessive hormonal stimulation on target cells • This proliferation is controlled – once the stimulus is removed, the proliferation regresses • This constitutes a fertile soil in which cancerous proliferations may occur CSBRP-V3-Dec-2011
- 66. Pathological hyperplasiaPathological hyperplasia Examples:Examples: EM hyperplasia – Estrogens Prostatic hyperplasia – Androgens Connective tissue hyperplasia – wound healing Warts – viral infections (HPV) CSBRP-V3-Dec-2011
- 76. Metaplasia in esophagusMetaplasia in esophagus CSBRP-V3-Dec-2011
- 86. Dystrophic calcification • Any cell death • Tumor necrosis • Atheroma • Tuberculosis CSBRP-V3-Dec-2011
- 87. Intracellular accumulations • Endogenous a- Lipid (alcohol) b- Protein (alcohol, Alzheimer’s, Enzyme deficiencies) c- Glycogen (Enzyme deficiencies) d- Pigment (Lipofuchsin / melanin) • Exogenous pigment - hemosiderin CSBRP-V3-Dec-2011
- 88. Mechanisms of injuryMechanisms of injury 1.1. Mechanical disruption – TraumaMechanical disruption – Trauma 2. Failure of membrane integrity 3. Altered metabolic pathways 4. DNA damage 5. Deficiency of essential metabolites 6. Free radical generation CSBRP-V3-Dec-2011
- 89. Mechanisms of injuryMechanisms of injury 1. Mechanical disruption – Trauma 2.2. Failure of membrane integrityFailure of membrane integrity 3. Altered metabolic pathways 4. DNA damage 5. Deficiency of essential metabolites 6. Free radical generation CSBRP-V3-Dec-2011
- 90. Mechanisms of injuryMechanisms of injury Failure of membrane integrityFailure of membrane integrity • Compliment mediated cell lysis • Altered ion pumps & channels • Altered membrane lipids • Cross-linking membrane proteins • Altered calcium homeostsis • Lysosomal release CSBRP-V3-Dec-2011
- 91. Mechanisms of injuryMechanisms of injury 1. Mechanical disruption – Trauma 2. Failure of membrane integrity 3.3. Altered metabolic pathwaysAltered metabolic pathways 4. DNA damage 5. Deficiency of essential metabolites 6. Free radical generation CSBRP-V3-Dec-2011
- 92. Mechanisms of injuryMechanisms of injury Altered metabolic pathwaysAltered metabolic pathways • Cell respiration • Decreased protein systhesis • Depletion of ATP & active transport system CSBRP-V3-Dec-2011
- 93. Mechanisms of injuryMechanisms of injury 1. Mechanical disruption – Trauma 2. Failure of membrane integrity 3. Altered metabolic pathways 4.4. DNA damageDNA damage 5. Deficiency of essential metabolites 6. Free radical generation CSBRP-V3-Dec-2011
- 94. Mechanisms of injuryMechanisms of injury DNA damage / lossDNA damage / loss • Immediate consequences • Delayed consequences CSBRP-V3-Dec-2011
- 95. Mechanisms of injuryMechanisms of injury 1. Mechanical disruption – Trauma 2. Failure of membrane integrity 3. Altered metabolic pathways 4. DNA damage 5.5. Deficiency of essential metabolitesDeficiency of essential metabolites 6. Free radical generation CSBRP-V3-Dec-2011
- 96. Mechanisms of injuryMechanisms of injury Deficiency of essential metabolitesDeficiency of essential metabolites • Oxygen depletion (Link) • Glucose depletion • Hormone deficiency CSBRP-V3-Dec-2011
- 97. Mechanisms of injuryMechanisms of injury 1. Mechanical disruption – Trauma 2. Failure of membrane integrity 3. Altered metabolic pathways 4. DNA damage 5. Deficiency of essential metabolites 6.6. Free radical generationFree radical generation CSBRP-V3-Dec-2011
- 98. Mechanisms of injuryMechanisms of injury Free radical generationFree radical generation [link] Damaged lipids, proteins, DNA et.c. CSBRP-V3-Dec-2011
- 99. Mechanisms of injuryMechanisms of injury 1. Mechanical disruption – Trauma 2. Failure of membrane integrity 3. Altered metabolic pathways 4.4. DNA damageDNA damage 5. Deficiency of essential metabolites 6. Free radical generation CSBRP-V3-Dec-2011
Notas del editor
- V1 June, 2007. V2 Nov, 2010. V3 Dec, 2011.
- Disease is not caused by acquisition of a new and different set of properties by the affected cell, but rather by quantitative alterations in existing functions and structure. ----------------------------------------- Rudolph Virchow (1821–1902) was one of the towering figures of nineteenth-century medicine, pathology, and social reform. He studied medicine in Berlin and taught there for a great part of his life, with interludes in Silesia and Würzburg. His primary field was pathology, to which he made prolific contributions, including the founding in 1847 of Archiv für pathologische Anatomie und Physiologie (known as &quot;Virchow&apos;s Archives&quot;), which still survives as a leading journal of pathology. Virchow&apos;s many discoveries include cells in bone and connective tissue; substances, such as myelin; and pathologies, such as embolism and leukemia. In 1855 he published his now-famous aphorism omnis cellula e cellula (&quot;every cell stems from another cell&quot;). He also stated that all diseases involve changes in normal cells--that is, all pathology ultimately is cellular pathology. Bibliography: Virchow, R. (1985). Collected Essays on Public Health and Epidemiology, ed. and trans. L. J. Rather. Canton, MA: Science History Publications.
- A basic cell is bounded by a cell membrane. Within the cell is a nucleus containing chromatin, often condensed at the periphery, along with larger clumps called chromocenters, and in some cells a nucleolus into which RNA is concentrated. The cytoplasm contains the cytosol and a variety of organelles, including mitochondria that power the cell via production of ATP, endoplasmic reticulum and ribosomes that synthesize new materials, a Golgi apparatus, and lysosomes.
- Cellular structure and function are determined by various cellular components. Glandular epithelial cells, such as the lining of the small intestine with a brush border, have microvilli. Glandular epithelial cells may have cytoplasmic mucin vacuoles. Epithelial cells are characterized by the presence of desmosomes that connect them. Many types of cells have cytoskeletal proteins. Squamous epithelial cells may have cytoskeletal elements such as tonofilaments. Cells with neuroendocrine differentiation tend to be rounded and may have cytoplasmic neurosecretory granules. The extracellular matrix (ECM) is composed of a variety of components. An adhesion complex in the cell links to integrin that extends outward. Seen here is a basement membrane. An important component of basement membrane is laminin, which acts as a &quot;lag bolt&quot; to connect cells via integrin to the ECM. Collagen (type IV in basement membrane and types V and VI as fine fibrils) comprises the structural component of ECM that provides shape and stability. Fibronectin is an adhesive protein that acts as a &quot;glue&quot; to hold the various components together.
- Genetic programmes, constraints of neighbouring cells, availability of metabolic substrates, finite metabolic pathways dictates the functioning of a cell. When the cell is functioning properly it’s said to be in a ‘steady state’, i.e. it can handle normal physiological demands.
- FIGURE 1-1 Stages of the cellular response to stress and injurious stimuli.
- FIGURE 1-8 Schematic illustration of the morphologic changes in cell injury culminating in necrosis or apoptosis.
- Differences between Ischemic and Hypoxic injury
- &lt; activity of Na+ pump [Link] Depletion of intracellular glycogen Lowered intracellular pH (acidosis) (&gt; anerobic glycolysis) ---&gt; clumping of chromatin Reduced protein synthesis (due to detachment of ribosomes from RER)
- FIGURE 1-17 Functional and morphologic consequences of decreased intracellular ATP during cell injury. The morphologic changes shown here are indicative of reversible cell injury. Further depletion of ATP results in cell death, typically by necrosis. ER, endoplasmic reticulum.
- FIGURE 1-18 Consequences of mitochondrial dysfunction, culminating in cell death by necrosis or apoptosis.
- FIGURE 1-19 The role of increased cytosolic calcium in cell injury. ER, endoplasmic reticulum.
- Autocatalytic action: molecules that react with free radicals are in turn converted in to free radicals.
- NOTE:Production of free radicals in the cell:1. due to insults (ex: chemical, radiation)2. as a part of normal respiration and other routine cellular activities.
- Nitric oxide (NO): an important chemical mediator normally synthesized by a variety of cell types that can act as a free radical or can be converted into highly reactive nitrite species. Radiation energy: Ionizing radiation can hydrolyse water into hydroxyl (HO.) and hydrogen (H.) free radicals.
- Lipid peroxidation of membranes: Double bonds in polyunsaturated lipids are vulnerable to attack by oxygen derived free radicals. The lipid radical ineteractions yeild peroxides, which are themselves unstable and reactive, and an autocatalytic chain reaction ensues. DNA fragmentation: free radicals react with thymine in DNA and produce single strand breaks. This results in cell killing and malignant transformation. Cross-linking of proteins: free radicals induce cross-linking at sulfhydral groups resulting in degradation and loss of enzymatic action. Free radicals also may cause polypeptide fragmentation.
- Figure 1-14 The role of reactive oxygen species in cell injury. O2 is converted to superoxide (O2-) by oxidative enzymes in the endoplasmic reticulum (ER), mitochondria, plasma membrane, peroxisomes, and cytosol. O2- is converted to H2O2 by dismutation and thence to OH by the Cu2+/Fe2+-catalyzed Fenton reaction. H2O2 is also derived directly from oxidases in peroxisomes. Not shown is another potentially injurious radical, singlet oxygen. Resultant free radical damage to lipid (peroxidation), proteins, and DNA leads to various forms of cell injury. Note that superoxide catalyzes the reduction of Fe3+ to Fe2+, thus enhancing OH generation by the Fenton reaction. The major antioxidant enzymes are superoxide dismutase (SOD), catalase, and glutathione peroxidase. GSH, reduced glutathione; GSSG, oxidized glutathione; NADPH, reduced form of nicotinamide adenine dinucleotide phosphate.
- If free radicals are produced in a normal cell, then how the cells are surviving? There are many protective mechanisms which neutralize the free radicals.
- Figure 1-14 The role of reactive oxygen species in cell injury. O2 is converted to superoxide (O2-) by oxidative enzymes in the endoplasmic reticulum (ER), mitochondria, plasma membrane, peroxisomes, and cytosol. O2- is converted to H2O2 by dismutation and thence to OH by the Cu2+/Fe2+-catalyzed Fenton reaction. H2O2 is also derived directly from oxidases in peroxisomes. Not shown is another potentially injurious radical, singlet oxygen. Resultant free radical damage to lipid (peroxidation), proteins, and DNA leads to various forms of cell injury. Note that superoxide catalyzes the reduction of Fe3+ to Fe2+, thus enhancing OH generation by the Fenton reaction. The major antioxidant enzymes are superoxide dismutase (SOD), catalase, and glutathione peroxidase. GSH, reduced glutathione; GSSG, oxidized glutathione; NADPH, reduced form of nicotinamide adenine dinucleotide phosphate.
- HgCl2 action: mercury binds to –SH group of various cell membrane proteins causing inhibition of ATPase dependent transport and increased membrane permeability.
- 2. Indirect action (altered chemical): For their action they must be converted to reactive toxic metabolites Metabolic conversion occurs in the P450 mixed function oxidases in the SER of liver Mechanism of injury: a- formation of reactive free radicals b- direct covalent binding to protein & lipids Ex: CCl4 and Acetaminophen
- Action of CCl4 : It’s converted in to toxic free radical CCl3 in the liver. Cause membrane phospholipid peroxidation, break down of ER. In &lt;30 min hepatic synthesis of proteins drops and in 2hrs swelling of SER and dissociation of ribosomes. There is reduced lipid export from the hepatocytes owing to their inability to synthesize aporpotein to complex with triglycerides - Fatty liver. Mitochondrial injury leads to drop in ATP and cell swelling. At the end Ca+ influx activates enzymes which results in cell death.
- Include: clinical application Include normal zones of liver acinus Explain importance of zonal division in liver Examples for hypoxic and chemical injury Liver zones Ex of toxic injury – zone-1 Ex of hypoxic injury in CHF – zone-3 Clnical senarios-CCH, anemia and DM, shock, anoxic brdamage in anemia Cystein given before radiation treatment for cancers Green tea, pumpkin, vit-c, e and beta caroteins
- Pateint with CCF.
- Patient in CCF
- Pateint with CCl4 poisoning
- Global injury – Long standing alcoholism
- A – Normal B – CCl4 poisoning C – Hypoxic damage D – Acetaminophene damage
- 1-Excretion 2-Excretion 3-Concentration of the chemical --------------------------------------- Include: clinical application Clnical senarios-CCH, anemia and DM, shock, anoxic brdamage in anemia Cystein given before radiation treatment for cancers Green tea, pumpkin, vit-c, e and beta caroteins
- Answer: RBCs
- Cell type: Neurons are highly susceptible to anoxia (5min) where as skeletal muscle can withstand for a very long time (60min). Pre-existing state: ex: nutritional state, age of the person et.c.
- Cell type: Neurons are highly susceptible to anoxia (5min) where as skeletal muscle can withstand for a very long time (60min). Pre-existing state: ex: nutritional state, age of the person et.c.
- Cells respond to increased demand and external stimulation by hyperplasia or hypertrophy and they respond to reduced supply of nutrients and growth factors by atrophy. In some situations, cells change from one type to another, a process called metaplasia
- Receptor: LDL receptor down regulation in cholesterol replete state Protein transcription: Heat shock protein synthesis may protect the cells from certain form of injury Switch of protein from one type to the other: cells driven to produce collagen / extracellular matrix protein in chronic inflammation & fibrosis Hence cellular adaptative responses can then occur at any of a number of steps. (receptor binding, protein synthesis--- transcription, translation or export)
- The mechanism of compensatory hyperpalsia is not understood well. May be due to proliferation of remaining cells and also due to development of new cells from stem cells.
- The prominent folds of endometrium in this uterus opened to reveal the endometrial cavity are an example of hyperplasia. Cells forming both the endometrial glands and the stroma have increased in number. As a result, the size of the endometrium has increased. This increase is physiologic with a normal menstrual cycle.
- This is an example of prostatic hyperplasia. The normal prostate is about 3 to 4 cm in diameter. The number of prostatic glands, as well as the stroma, has increased. The pattern of increase here is not uniform, but nodular. This increase is in response to hormonal manipulation, but in this case is not a normal physiologic process.
- Here is one of the nodules of hyperplastic prostate. The cells making up the glands are normal in appearance, there are just too many of them.
- This is cardiac hypertrophy involving the left ventricle. The number of myocardial fibers does not increase, but their size can increase in response to an increased workload, leading to the marked thickening of the left ventricle in this patient with systemic hypertension. Normal wall thickness: LV-1.3to1.5cms RV-0.3to0.5cms
- There are some muscle fibers here that show atrophy. The number of cells is the same as before the atrophy occurred, but the size of some fibers is reduced. This is a response to injury by &quot;downsizing&quot; to conserve the cell. In this case, innervation of the small fibers in the center was lost. This is a trichrome stain.
- The testis at the right has undergone atrophy and is much smaller than the normal testis at the left.
- This is cerebral atrophy in a patient with Alzheimer&apos;s disease. The gyri are narrowed and the sulci widened toward to frontal pole.
- Metaplasia of laryngeal respiratory epithelium has occurred here in a smoker. The chronic irritation has led to an exchanging of one type of epithelium (the normal respiratory epithelium at the right) for another (the more resilient squamous epithelium at the left). Metaplasia is not a normal physiologic process and may be the first step toward neoplasia.
- Metaplasia of esophageal squamous mucosa has occurred here, with gastric type columnar mucosa at the left.
- This is dysplasia. The normal squamous epithelium at the left transforms to a disorderly growth pattern at the right. This is farther down the road toward neoplasia.
- Discuss the differences between dystrophic and metastatic calcifications.