Podcast
Questions and Answers
What are the two types of cell death?
What are the two types of cell death?
Which type of cell death is characterized by enzymatic digestion of dead cellular elements?
Which type of cell death is characterized by enzymatic digestion of dead cellular elements?
Which type of necrosis is most commonly associated with ischemia?
Which type of necrosis is most commonly associated with ischemia?
What type of necrosis is often seen in tuberculosis?
What type of necrosis is often seen in tuberculosis?
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Which of the following types of necrosis is characterized by a viscous liquid?
Which of the following types of necrosis is characterized by a viscous liquid?
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What is the term used to describe the chalky, white areas in fat necrosis?
What is the term used to describe the chalky, white areas in fat necrosis?
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Apoptosis is a vital process that helps eliminate unwanted cells, while necrosis is always pathologic.
Apoptosis is a vital process that helps eliminate unwanted cells, while necrosis is always pathologic.
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Which pathway of apoptosis is initiated by cellular injury, DNA damage, or loss of hormonal stimulation?
Which pathway of apoptosis is initiated by cellular injury, DNA damage, or loss of hormonal stimulation?
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Which pathway of apoptosis is initiated by external signals, such as FAS ligand or TNF?
Which pathway of apoptosis is initiated by external signals, such as FAS ligand or TNF?
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Which of the following is NOT a consequence of decreased intracellular ATP during cell injury?
Which of the following is NOT a consequence of decreased intracellular ATP during cell injury?
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Increased cytosolic calcium can activate various enzymes, such as ATPases, phospholipases, and endonucleases, leading to membrane damage.
Increased cytosolic calcium can activate various enzymes, such as ATPases, phospholipases, and endonucleases, leading to membrane damage.
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What is the term used to describe the process where cells digest their own organelles?
What is the term used to describe the process where cells digest their own organelles?
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What type of necrosis would be most likely to occur in a limb that has lost its blood supply and undergone coagulative necrosis, involving multiple tissue layers?
What type of necrosis would be most likely to occur in a limb that has lost its blood supply and undergone coagulative necrosis, involving multiple tissue layers?
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In a clinical setting, what type of necrosis is often associated with the finding of a hypoattenuated area on a CT scan in the territory of the left middle cerebral artery?
In a clinical setting, what type of necrosis is often associated with the finding of a hypoattenuated area on a CT scan in the territory of the left middle cerebral artery?
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Study Notes
Cell Injury Overview
- Cell injury is categorized into reversible and irreversible
- Reversible cell injury can be reversed if the stimulus is removed or the cause of injury is mild.
- Irreversible cell injury is severe and permanent, causing cell death (necrosis or apoptosis).
Causes of Cell Injury
- Oxygen Deprivation (Hypoxia, Ischemia): Most common cause
- Chemical Agents and Drugs
- Physical Agents: Trauma, extreme temperature, radiation, electric
- Infections
- Immunological Reactions
- Genetic Defects
- Nutritional Imbalances (deficiency or excess)
- Aging
Progression of Cell Injury and Death
- Myocardial cells become non-contractile after 1-2 minutes of ischemia.
- They do not die until 20-30 minutes of ischemia.
- Reversible changes are evident by biochemical alterations, cell function changes and light/ultrastructural microscopic changes within 2-3 hours after cell death.
- Irreversible changes show up in microscopy after 6 to 12 hours.
Reversible Cell Injury
- Cellular swelling (hydropic change or vacuolar degeneration): Water influx due to the failure of energy-dependent ion pumps in the plasma membrane
- Plasma membrane: Blebbing, blunting, or distortion of microvilli; loosening of intercellular attachments.
- Fatty change: Manifestation of lipid vacuoles in the cytoplasm.
- Redder cytoplasm (eosinophilic): Cytoplasm takes on a reddish color.
Mitochondrial, Membranes, and Nucleus features
- Mitochondrial swelling & phospholipid-rich amorphous densities
- Dilation of the ER with detachment of ribosomes
- Myelin figures are collections of phospholipids in damaged cells
- Nuclear alterations: clumping of chromatin
Irreversible Cell Injury (Cell death)
- Inability to restore mitochondrial function
- Breakdown of plasma and intracellular membranes
- Loss of DNA and chromatin integrity
Types of Cell Death
- Necrosis: Enzymatic digestion of dead cellular elements (often with inflammation).
- Apoptosis: A programmed cell death process, vital for eliminating unwanted cells (no inflammation).
Necrosis
- Definition: A spectrum of morphological changes following cell death.
- Characteristics: Death of a group of cells within a living organism, often followed by inflammation. Not physiologic, rather due to a pathological process.
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Types of Necrosis:
- Coagulative Necrosis (most common, typically in solid organs except brain)
- Liquefactive Necrosis (often in bacterial and fungal infections, brain)
- Caseous Necrosis (characteristic of tuberculosis)
- Fat Necrosis
- Fibrinoid necrosis (typically in immune reactions and vessel walls, e.g., in malignant hypertension and vasculitis)
- Gangrenous Necrosis (occurs in ischemia, can be dry or wet)
Necrosis: Morphological Features
- Necrotic cell is eosinophilic (pink), glassy, and potentially vacuolated.
- Cell membranes are fragmented.
- Nuclear changes include:
- Pyknosis (shrinkage, dense nucleus)
- Karyorrhexis (fragmentation of nucleus)
- Karyolysis (dissolution of nucleus)
- Inflammatory cells are present.
Apoptosis
- Definition: Programmed cell death (suicide) with intact cell membranes.
- Characteristics: Involves single cells or small groups of cells; no inflammatory response.
- Mechanisms: Apoptosis mechanisms involve multiple signaling pathways often depending on energy-dependent processes that lead to protein cleavage and subsequent cellular death.
- Significance: Prevents neoplastic transformation.
Autophagy
- An adaptation to nutrient deprivation.
- Cells digest their own organelles and recycle their contents, as a source of energy and substrates. If the stress is too severe, autophagy will result in death via apoptosis.
Mechanism of Cell Injury
- Cellular responses to injuries depend on injury type, duration, severity.
- The response depends on the type, status, adaptability and genetic makeup of the injured cell.
- Key mechanisms include ATP depletion, mitochondrial damage, calcium influx, reactive oxygen species, and membrane damage.
Calcium Influx and Loss of Calcium Homeostasis
- Calcium ions act as second messengers.
- Intracellular Ca++ is sequestered in mitochondria and ER
- Excessive cytosolic Ca++ can activate enzymes (ATPases, phospholipases, endonucleases) triggering membrane damage.
- The resulting membrane damage is also responsible for necrosis.
Membrane Damage
- Increased permeability of cellular membranes due to damage to plasma, lysosomal, and mitochondrial membranes.
- This often culminates in necrosis.
Additional Information
- Detailed mechanisms are explained using diagrams of signaling pathways
- A case study regarding a 64-year-old female stroke patient is used to highlight the relevance of the concepts discussed, specifically regarding liquefactive necrosis.
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