2. Cell Injury I Flashcards
What are the common causes of injury/ stress to ocular tissues? (8 points)
• Hypoxia
• Chemicals & Drugs
• Physical Agents
• Microbiologic Agents
• Immunological Agents
• Genetic defects
• Nutritional Imbalances
• Aging
There are different types of cell adaptations:
* ... is the decrease in cellular size and loss of ...
* ... is the increase in ...
* ... is the increase in ...;
* ... is the ... of one cell type with another by ...;
* ... is abnormal change in .... This is a ... during growth. Otherwise, it can be abnormal and ....
There are different types of cell adaptations:
* Atrophy is the decrease in cellular size and loss of organelles
* Hypertrophy is the increase in normal cellular size
* Hyperplasia is the increase in normal cell number/ density;
* Metaplasia is the replacement of one cell type with another by differentiation/ proliferation;
* Dysplasia is abnormal change in cell shape/ size. This is a normal developmental process during growth. Otherwise, it can be abnormal and pre-cancerous.
Cell adaptation can be observed in ... tissues.
* ... syndrome causes the loss of melanosomes in the ..., this is peripupillary ...;
* Retinal pigment epithelial cells can grow ... and ..., this is hypertrophy;
* Hyperplasia of the corneal epithelium can arise from ... or ... irritation, ... and ...;
* After trauma, lens epthelial cell can undergo ... into ... lens cells. This transition causes the formation of ... in the lens ... and thus cause ... cataract, this is ...;
* After an infection with ..., the ... epithelium can increase in thickness, the abnormal growths are self-limiting, ... and ..., this is ....
Cell adaptation can be observed in ocular tissues.
* Pseudoexfoliation syndrome causes the loss of melanosomes in the iris pigment epithelial cells, this is peripupillary atrophy;
* Retinal pigment epithelial cells can grow abnormally in size and increase pigment density, this is hypertrophy;
* Hyperplasia of the corneal epithelium can arise from chemical or physical irritants, microbial infections and nutritional deficiencies;
* After trauma, lens epthelial cell can undergo EMT transformation into mesenchymal lens cells. This transition causes the formation of opacity in the lens capsule and thus cause anterior subcapsular cataract, this is metaplasia;
* After an infection with HPV, the conjunctival epithelium can increase in thickness, the abnormal growths are self-limiting, non-invasive and neovascular, this is dysplasia.
What does reversible and irreversible cell injury mean?
Reversible cell injury is when cells are able to return to their stable baseline once the damaging stimulus is removed.
Irreversible cell injury occurs with persistent or rapid injuries, which causes apoptosis.
What are the causes of cell injury?
• Ischemia
• Infections
• Toxins
• Immune reactions
During reversible injury, cell becomes under ... and thus undergo various changes. These changes include ..., ... and ..., and .... The corneal epithelium is a ... tissues, where ... can replace damaged epithelial cells in most cases;
During irreversible injury, cell undergoes .... This causes ..., where the nucleus pales and starts to fade due to ... and .... The nucleus will then ... and ... via ... and ... respectively. The mitochondria will also undergo ....
Post-irreversible cell injury, the cell will undergo ....
During reversible injury, cell becomes under stress and thus undergo various changes. These changes include blending, clumping of chromatin and nucleus, and mitochondrial swelling. The corneal epithelium is a regenerative tissues, where limbal stem cells can replace damaged epithelial cells in most cases;
During irreversible injury, cell undergoes apoptosis. This causes karyolysis, where the nucleus pales and starts to fade due to DNAases and RNAases. The nucleus will then shrink and fragment via pyknosis and karyorrhexis respectively. The mitochondria will also undergo vacuolisation.
Post-irreversible cell injury, the cell will undergo either apoptosis or necrosis.
What is apoptosis and necrosis?
Apoptosis is the active, programmed process of autonomous cellular dismantling that avoids eliciting inflammation. This process is homeostatic and pathological. The cellular contents broken down are enclosed in membrane, therefore doesnt elicit inflammation;
Necrosis is the passive, rapid and accidental cell death resulting from environmental disturbances with uncontrolled release of inflammatory cellular contents, including enzymes and proteases. These contents causes secondary inflammatory responses.
Compare and contrast the differences between apoptosis and necrosis, in terms of cell size, nucleus, plasma membrane, cellular contents, adjacent inflammation and their physiological or pathological roles.
Apoptosis occurs with reduced cell size. Their nucleus fragments and the plasma membrane remains unbroken but altered. Cellular contents are released in apoptotic bodies and therefore doesnt cause any adjacent inflammation. This is a physiological process of removing unwanted cells. It can also be pathological with DNA or protein damages;
Necrosis occurs with enlarged cells.The nucleus will undergo pyknosis, karyorrhexis and karyolysis. The plasma membrane is distracted therefore the cellular contents can leak out and cause adjacent inflammation. Necrosis is invariably pathological.
What can occur when physiological apoptosis does not occur normally in the lens?
Persistent hyaloid artery remnant at the lens. This is a developmental remnant, where the surface of the lens was vascularised during development (tunica vascular lentis).
What are the major disturbances that can contribute to apoptosis? (4 points)
- Disturbances to mitochondria and their ability to generate ATP and ROS
- Disturbance in calcium homeostasis
- Damage to cellular (plasma and lysosomal) membranes
- Damage to DNA and misfolding of proteins.
There are two major pathways of apoptosis: ... (intrinsic) pathway and ... (extrinsic) pathway. Both of these pathways converge and are mediated by ....
The ... pathway is triggered by cell injury, including stress towards ..., ... and ....
The ... pathway is triggered by the ... to TNF receptors.
Both pathways activate ... and causes activation of ... and breakdown of .... Cell then blebs into ... and these are removed by ....
There are two major pathways of apoptosis: Mitchondrial (intrinsic) pathway and Death receptor (extrinsic) pathway. Both of these pathways converge and are mediated by capases.
The mitochondrial pathway is triggered by cell injury, including stress towards mitochondria, DNA damage and protein misfolding.
The death receptor pathway is triggered by the Fas ligand binding to TNF receptors.
Both pathways activate caspases and causes activation of endonucleases and breakdown of cytoskeleton. Cell then blebs into apoptotic bodies and these are removed by phagocytes.
Necrosis is ... and occurs as a result of .... It is characterised by the loss of ... function, such that there is excess Na+, causes activation of ..., and therefore .... It is also characterised by the activation of ... enzymes (endo-, proteo-, phospholip-, ases). Cells undergoing necrosis will also ... and ....
Necrosis is passive and occurs as a result of acute ATP depletion. It is characterised by the loss of ion channel function, such that there is excess Na+, causes activation of Na+K+ATPase, and therefore depletion of ATP. It is also characterised by the activation of Ca2+ dependent enzymes (endo-, proteo-, phospholip-, ases). Cells undergoing necrosis will also swell and bleb.
What biochemical methods has been used to detect cell apoptosis?
TUNEL → BrdU + fluoscent labelling of terminal ends of nucleic acids
Fluorescently labelling Annexin-V antibody = protein exposed during membrane damage (RGC apoptosis)
