Test: Cell Injury- 1 - NEET PG MCQ

In the initiation of the extrinsic pathway of apoptosis, the following occurs:

• The Fas ligand binds to CD95 (Fas), which is part of the TNF receptor family.
• Alternatively, TRAIL (TNF-related apoptosis-inducing ligand) interacts with the death receptors DR4 and DR5.

This interaction promotes the assembly of FADD (Fas-associated death domain) and procaspase-8 to the death domain motifs of the receptors, leading to the activation of caspase 8 (and in humans, caspase 10). This process ultimately activates the effector caspases - caspases-3 and -7.

• Interstitial tissues of the gastric mucosa
• Kidneys
• Lungs
• Systemic arteries
• Pulmonary veins

• Cell injury
• No disturbance in calcium metabolism

Hemosiderin is a pigment that accumulates in situations of iron overload.

Anthracotic pigment refers to the pigment found in the lungs of individuals exposed to coal.

Atheromatous plaque contains necrotic cells, leading to the occurrence of dystrophic calcification.

• Mnemonic: D represents Dead and D stands for Dystrophic.

Free radicals are produced via Fenton’s reaction, represented as:

H₂O₂ + Fe²⁺ → Fe³⁺ + OH⁺ + OH⁻

• In this process, iron transitions from its ferrous to ferric state, resulting in the formation of a radical.
• While other processes also lead to free radical damage, the focus here is on the Fenton reaction.

The impacts of these reactive species on cellular injury encompass:

• Lipid peroxidation of membranes,
• Oxidative modification of proteins, and
• DNA lesions.

Mallory bodies are formed when scattered hepatocytes gather entangled bundles of cytokeratin intermediate filaments along with other proteins. These are observed as eosinophilic cytoplasmic inclusions within degenerating hepatocytes.

• Dystrophic calcification
• Metastatic calcification

• The first is the inability to reverse mitochondrial dysfunction, which includes a lack of oxidative phosphorylation and ATP generation, even after the original injury has been resolved.
• The second relates to the emergence of significant disturbances in membrane function.

Caspases are cysteine proteases that play an essential role in the process of apoptosis. Apoptosis is necessary for:

• Removing cells that are no longer needed
• Maintaining a stable number of different cell populations within tissues

This programmed cell death is crucial during various stages of embryogenesis, including:

• Implantation
• Organogenesis
• Developmental involution
• Metamorphosis

The morphologic characteristics typical of apoptosis encompass:

• Cell shrinkage: The cell exhibits a reduction in size, with dense cytoplasm and closely packed organelles.
• Chromatin condensation: This is the most distinctive feature of apoptosis.
• Formation of cytoplasmic blebs and apoptotic bodies.

Concerning option ‘a’: Plasma membranes are believed to stay intact until the later stages of apoptosis, similar to a normal cell. In relation to option “b”, eosinophilic cytoplasm is a common trait observed in both necrosis and apoptosis. For option “c”, nuclear moulding is described as “the shape of one nucleus adapting to the contours of an adjacent nucleus”. This is a feature found in malignant cells.

• Dry gangrene is associated with coagulative necrosis.
• Wet gangrene involves liquefactive necrosis.

• Features of Reversible Cell Injury
  • Cellular swelling
  • Loss of microvilli
  • Formation of cytoplasmic blebs
  • Endoplasmic reticulum swelling
  • Detachment of ribosomes
  • Myelin figures
• Features of Irreversible Cell Injury
  • Clumping of nuclear chromatin
  • Large flocculent, amorphous densities in swollen mitochondria due to increased calcium influx
  • Swelling and disruption of lysosomes and leakage of lysosomal enzymes into the cytoplasm
  • Decreased basophilia
  • Severe damage to plasma membranes
  • Nuclear changes include:
    • Pyknosis (nuclear condensation)
    • Karyorrhexis (nuclear fragmentation)
    • Karyolysis (nuclear dissolution)

• Regions exhibiting fibrinoid necrosis are observed as blurred eosinophilic areas with hidden underlying cellular structures.
• This type of necrosis is associated with conditions such as malignant hypertension, vasculitis (including PAN), and acute rheumatic fever.

Apoptosis, also known as programmed cell death, can be triggered via intrinsic or extrinsic pathways. In the intrinsic pathway:

• cytochrome c (cyt c) associates with APAF-1
• this interaction activates caspases
• leading to cell death

For further details, refer to the text.

Apoptotic cells display phosphatidylserine on the outer layers of their plasma membranes. This phospholipid translocates from the inner layers, where it is recognised by various receptors on phagocytes.

• These lipids are also identified through the binding of a protein known as Annexin V.
• Consequently, Annexin V staining is employed to detect apoptotic cells.

Cytosolic cytochrome C and Apaf-1 play roles in the intrinsic pathway of apoptosis. It is the mitochondrial cytochrome C, rather than the cytosolic form, that is involved in aerobic respiration.

• cleave proteins
• trigger apoptosis

In apoptosis, the deceased cell is swiftly removed before its contents can escape, meaning that cell death via this mechanism does not provoke an inflammatory response in the host.

Two phenomena consistently define irreversible cell damage:

• Significant amorphous densities within the mitochondria, indicating an inability to reverse mitochondrial dysfunction.
• Severe impairment of membrane function.

The cleavage of DNA between nucleosomes into oligonucleosomes, typically in multiples of 180-200 base pairs, occurs due to the action of endonucleases that depend on Ca²⁺ and Mg²⁺. This process is a hallmark of apoptosis.

endonucleases are enzymes that facilitate the internucleosomal cleavage of DNA into oligonucleosomes. These oligonucleosomes can be observed through agarose gel electrophoresis, appearing as DNA ladders. In cases of necrosis, a smeared pattern is typically observed.

• Key characteristics of apoptosis include the development of cytoplasmic blebs and apoptotic bodies.
• Cell shrinkage: The cells reduce in size, with a denser cytoplasm.
• Chromatin condensation: This is the most distinctive feature of apoptosis.
• Absence of inflammation during the process.
• Gel electrophoresis of DNA reveals a ‘step ladder’ pattern.