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Causes of Cell Injury Include:
- Oxygen depravation
- Chemical exposure
- Radiation exposure
- Inorganic mineral exposure
- Infectious Agents
- Chronic inflammation
- Immune mediated injury
- Genetic defects
- Nutritional imbalances
- Physical agents or trauma
- Aging
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Injury Degrees
- Mild: Temporary adaptation
- Reversible
- Moderate: Reversible Cell injury
- Reversible
- Severe
- Cell death (irreversible)
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Cellular Adaptations
- Physiological and/or pathological responses to changes or injury
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
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Atrophy
- Greek: without nourishment (trophy)
- Shrinkage of cells
- Ultimately shrinkage of organ
- Due to loss of cell substance
- Atrophied cells: reduced functional capabilities
- Decreased workload
- … use it or lose it
- Diminished blood or nutrition
- Decreased endocrine stimulation
- e.g., post menopausal uterus
- Loss of nerve supply
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Hypertrophy
- Increase in cell size
- Due to synthesis of more cellular components
- Potential causes
- Increased functional demand
- e.g., Heart, skeletal muscle
- Hormonal stimulus
- smooth muscle of uterus during pregnancy
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Hyperplasia
- Increase in cell number (does not occur in terminally differentiated cells)
- Potential causes
- Physiological
- -Hormone (e.g., breast and uterus during pregnancy)
- -Compensatory (e.g., liver regeneration)
- -Wound healing
- Pathological
- -abnormal hormone stimulation
- -endometrial hyperplasia; prostatic hyperplasia
- --sometimes fertile ground for cancer formation
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Metaplasia
- One type of cell changes into another
- Pathological process (can be reversible)
- Examples
- -Acid reflux-Stomach - esophagus junction
- -Smokers-Squamous metaplasia (bronchial epithelium)
- --columnar epithelium w cilia in bronchial epithelium > stratified squamous epithelium- to deal with abnormal stress of smoking;
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Reversible injury
- If the cell does not die and
- If the cell can recover when the injurious stimulus is removed
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Reversible injury causes
- Hypoxia
- Lack of Oxygen required for ATP production
- Chemicals
- Infectious Agents
- Virus, bacteria, parasites, etc.
- Immune mediated injury
- e.g., autoimmune disease
- Genetic diseases
- Physical injury / trauma
- e.g., puncture, electrical, radiation, temperature
- Nutritional imbalances
- Aging
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Hypoxia
- O2 down->lower oxidative phosphoralation-> lower ATP
- Oxygen deprivation (stroke, coronary artery disease)
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ATP delpletion
- ATP is depleted,
- Calcium pumps stop working and calcium can enter the cell
- (levels are much higher outside the cell compared to inside under normal conditions).
- Among other things increased calcium within a cell can activate destructive enzymes such as:
- Phospholipase: damage to the cell membrane
- Proteases: degrade vital proteins (e.g., cytoskeleton and others)
- Endonucleases: cause DNA degradation
- -cells in our body depend on oxygen for metabolism in oxidative phosphorylation; if oxygen is decreased, oxidative phosphorylation decreases, which in turn decreases ATP production, ion pump activity, metabolism, and protein synthesis
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Ischemia
Decreased blood supply, if persists can be irreversible
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Hypoxia and Ischemia morphological changes
- Acute Swelling
- Pump dysfunctions
- Membrane “blebbing”
- Cytoskeleton disruption
- ER and Mitochondira Swelling
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Kidney slide
- Compare normal kidney epithelium vs. early signs of injury. For early (potentially reversible changes) not that cells are swelling, the cells are more pink (eosinophilic),, and if you look closely, there is membrane blebbing.
- -left: normal kidney epithelium, with cuboidal epithelium surrounding lumen
- -right: if there is ischemic & hypoxic situation
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Fatty Liver
- Often times, various intracellular accumulations are signs of cell and tissue injury. Here a chronic alcoholic has what is called “fatty liver”. The liver cells (hepatocytes) have accumulations of fatty acids due to alcohol- induced cell injury. This is due to the protein synthesis and product section machinery being suboptimal (so lipids and their binding products) are not secreted as optimally as usual. Therefore, fat accumulates.
- -right: abnormal cells- abnormal accumulation of products; for heavy drinkers, liver will show accumulation of fat, which shows dysfunctional activity of hepatocytes (liver cells)
- accumulation of normal products of cells, but that shouldn’t be in THAT particular organ’s cells (ex fat in the liver)
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Irreversible injury
- Causes of Cell Injury Include excess or prolonged exposure to:
- Hypoxia / ischemia
- Chemicals and other toxins
- Infectious Agents
- Immune mediated injury
- Inflammation
- Genetic diseases
- Physical injury / trauma
- Persistent nutritional imbalance
- Aging
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NECROSIS:
- General term for death of a collection of cells or tissue
- Necrosis: “…there is necrosis”
- Necrotic: “…necrotic tissue”
- Death due to pathology
- Little or no normal cell form (morphology)
- degradation of cell due to leakage of enzymes
- Often influx of immune cells
- different types/appearances
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Coagulative Necrosis
- Injury cased by ischemia or burns
- The shape and architecture of tissue may stay intact (temporarily), but cells are dead
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Reactive Oxygenated Species
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Liquefactive Necrosis
- Inflammatory response gone wild
- Extreme: fungal or bacterial infection
- “Pus” formation
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Necrosis Histology
- many nuclei are missing (they have been degraded)
- many of the nuclei are pyknotic. The border of the cells are gone.
- ghosts/shadows of cells, and either no nuclei or ghosts of nuclei
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Ultimate Cell death causes
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Calcium cell death
- pump control is lost and plasma membrane becomes permeable to ions and injurious agents
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Reperfusion Injury
- Prolonged ischemia can lead to cell death
- Sometimes, with modest ischemia, there can be massive cell death upon re-introducing the blood flow (oxygen)
- Called Ischemic - Reperfusion injury
- Thought to be caused in part by spike in ROS synthesis with O2
- From parenchyma
- From inflammatory cells
- Allow cells to slowly recover
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Apoptosis
- Programmed cell death
- Regulated process
- Cascade of intracellular proteins are triggered which cause fragmentation of nucleus
- No / limited inflammatory response
- Apoptotic cells immediately eaten by Macrophages
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