Cellular Adaptations, Injury, and Death Practice Flashcards

Flashcards covering cellular adaptations, reversible and irreversible cell injury, types of necrosis, mechanisms of apoptosis, free radical damage, and pathologic calcification based on the lecture transcript.

Ubiquitin-Proteasome pathway

The mechanism of protein degradation seen during cellular atrophy where proteins are tagged with ubiquitin and degraded by the proteasome.

Lipofuscin

A microscopic pigment that is a hallmark sign of tissue atrophy and "wear-and-tear" free radical injury.

Permanent cells

Cell types such as skeletal and cardiac muscle that have lost their capacity for mitotic division and can only undergo hypertrophy, not hyperplasia.

Metaplasia

A reversible cellular adaptation where one cell type is replaced by another (e.g., stratified squamous to columnar) in response to chronic irritation, such as in Barrett's Esophagus.

Cellular swelling

Also known as hydropic change or vacuolar degeneration, it is the first morphological manifestation of almost all forms of reversible cell injury due to failure of energy-dependent ion pumps.

ATPase pump

The energy-dependent plasma membrane transporter whose failure directly leads to acute hydropic swelling during hypoxia.

Reversible hypoxic cell injury features

Morphological changes including plasma membrane blebs, blunting or loss of microvilli, mitochondrial swelling, and endoplasmic reticulum swelling with ribosomal detachment.

Irreversible cell injury hallmarks

The two main criteria for the "point of no return": 1. Inability to reverse mitochondrial dysfunction (lack of ATP generation) and 2. Profound membrane integrity defects.

Myocardial ischemia threshold

Approximately $20 \text{ to } 40\text{ minutes}$ is the duration myocardial cells can tolerate severe ischemia before irreversible injury and cell death occur.

Pyknosis

A nuclear change characterized by shrinkage and increased basophilia (dark blue condensation) of chromatin.

Karyorrhexis

The fragmentation of a pyknotic nucleus.

Karyolysis

The dissolution of the nucleus where basophilia fades due to DNase activity.

Coagulative necrosis

A pattern of necrosis characterized by preserved underlying basic tissue architecture for several days because the injury denatures both structural proteins and lytic enzymes.

Liquefactive necrosis

A type of necrosis classic to central nervous system (brain) hypoxic infarctions where enzymatic digestion by microglial hydrolases predominates.

Caseous necrosis

Necrosis uniquely associated with Mycobacterium tuberculosis, showing a friable, cottage-cheese-like gross appearance and granulomatous inflammation.

Langhans giant cells

Giant cells seen in granulomatous inflammation where nuclei are arranged peripherally in a horseshoe shape, classic for TB.

Foreign body giant cells

Giant cells where nuclei are scattered haphazardly.

Saponification

The biochemical hallmark of enzymatic fat necrosis occurring when activated pancreatic lipases break down triglycerides into fatty acids which then combine with calcium.

Fibrinoid necrosis

A pattern of necrosis seen in immune-mediated vascular damage, showing a bright pink, amorphous appearance on H&E stain due to immune complex and fibrin deposits.

Caspases

Cysteine-Aspartic Proteases that serve as the primary executioners of apoptosis.

Bcl-2

An anti-apoptotic protein (along with Bcl-xL) that stabilizes the mitochondrial outer membrane to prevent cytochrome c leakage.

Bax and Bak

Pro-apoptotic sensor proteins that form channels in the mitochondrial membrane to release cytochrome c.

Apaf-1

Apoptotic protease-activating factor 1, the cytosolic factor that binds with Cytochrome c to form the "apoptosome."

Extrinsic pathway receptors

Cell surface receptors including Fas ($CD95$) and $TNFR1$ (Tumor Necrosis Factor Receptor 1) that trigger apoptosis.

DNA laddering

A diagnostic biochemical marker for apoptosis resulting from internucleosomal cleavage, yielding a specific pattern on gel electrophoresis.

Free radical damage mechanisms

The three primary mechanisms include: 1. Lipid peroxidation of membranes, 2. Oxidative modification of proteins, and 3. DNA damage.

Free radical scavenging enzymes

1. Superoxide Dismutase (SOD), 2. Catalase, and 3. Glutathione Peroxidase.

Steatosis

Fatty change in the liver, most commonly caused by alcohol abuse in developed countries.

Anthracosis

The accumulation of exogenous carbon or coal dust pigment in alveolar macrophages, turning lungs and lymph nodes black.

Hemosiderosis

Localized or systemic iron overload without tissue damage.

Hemochromatosis

Severe systemic iron overload resulting in classic parenchymal damage such as liver cirrhosis, pancreatic fibrosis, and skin bronzing.

Dystrophic Calcification

Calcium deposition in dead, dying, or degenerated tissues occurring with normal serum calcium levels.

Metastatic Calcification

Calcium deposition in normal tissues due to hypercalcemia (abnormally elevated serum calcium levels).

Ischemia-Reperfusion Injury

Injury occurring when reoxygenation of ischemic tissue triggers an abrupt, massive influx of oxygen free radicals (ROS) and activates inflammatory cascades.