Cell Injury, Cell Death, and Adaptations

Question 1

What are the four aspects of a disease process that form the core of pathology?

Answer 1

The four aspects are:
*Causation (etiology)
*Biochemical and molecular mechanisms (pathogenesis)
*Associated structural (morphologic changes) and functional alterations in cells and organs
*Resulting clinical consequences (clinical manifestations)

Question 2

How does hypoxia contribute to cell injury, and what are its common causes?

Answer 2

Hypoxia, a deficiency of oxygen, reduces aerobic oxidative respiration, leading to cell injury and death. Common causes include reduced blood flow (ischemia), cardiorespiratory failure, and decreased oxygen-carrying capacity of the blood (anemia, carbon monoxide poisoning).

Question 3

What is the earliest manifestation of almost all forms of injury to cell?

Answer 3

Cellular swelling is the earliest manifestation, causing pallor, increased turgor, and increased weight of the affected organ.

Question 4

What is hydropic change or vacuolar degeneration, and how is it characterized?

Answer 4

Hydropic change or vacuolar degeneration refers to the pattern of nonlethal injury characterized by small clear vacuoles within the cytoplasm, representing distended and pinched-off segments of the endoplasmic reticulum (ER).

Question 5

How does injured cell cytoplasm appear under microscopic examination with hematoxylin and eosin (H&E) staining?

Answer 5

Injured cell cytoplasm appears red (eosinophilic) due to loss of RNA, which binds the blue hematoxylin dye. The eosinophilia becomes more pronounced with progression toward necrosis.

Question 6

What are the ultrastructural changes observed in reversible cell injury, as visible by electron microscopy?

Answer 6

The ultrastructural changes include:

1. Plasma membrane alterations (blebbing, blunting, loss of microvilli)
2. Mitochondrial changes (swelling, appearance of small amorphous densities)
3. Accumulation of “myelin figures” in the cytosol composed of phospholipids derived from damaged cellular membranes
4. Dilation of the endoplasmic reticulum (ER) with detachment of polysomes
5. Nuclear alterations with disaggregation of granular and fibrillar elements

Question 7

How is necrosis characterized at the cellular level?

Answer 7

Necrosis is characterized by denaturation of cellular proteins, leakage of cellular contents through damaged membranes, local inflammation, and enzymatic digestion of the lethally injured cell.

Question 8

What happens when lysosomal enzymes enter the cytoplasm of a necrotic cell?

Answer 8

Lysosomal enzymes digest the cell, and cellular contents leak through the damaged plasma membrane into the extracellular space, eliciting an inflammatory response.

Question 9

What are damage-associated molecular patterns (DAMPs), and what role do they play in necrosis?

Answer 9

DAMPs are substances released from injured cells, such as ATP and uric acid. They are recognized by receptors on macrophages and other cells, triggering phagocytosis of debris and production of cytokines that induce inflammation.

Question 10

What are the two phenomena that consistently characterize irreversible cell injury?

Answer 10

The two phenomena are the inability to reverse mitochondrial dysfunction (lack of oxidative phosphorylation and ATP generation) and profound disturbances in membrane function.

Question 11

How does injury to lysosomal membranes contribute to necrosis?

Answer 11

Injury to lysosomal membranes results in the enzymatic dissolution of the injured cell, which is characteristic of necrosis.

Question 12

What causes the increased eosinophilia in necrotic cells observed in H&E stains?

Answer 12

Increased eosinophilia in necrotic cells is due to the loss of cytoplasmic RNA and the accumulation of denatured cytoplasmic proteins, which bind the red dye eosin.

Question 13

How does the cytoplasm of necrotic cells appear, and why?

Answer 13

The cytoplasm of necrotic cells may have a glassy homogeneous appearance due to the loss of glycogen particles, and when enzymes digest the cell’s organelles, it becomes vacuolated and appears moth-eaten.

Question 14

What are myelin figures, and what happens to them?

Answer 14

Myelin figures are large whorled phospholipid precipitates formed from dead cells. They are either phagocytosed by other cells or further degraded into fatty acids, and their calcification results in calcium-rich precipitates.

Question 15

Describe the three nuclear changes that occur in necrotic cells

Answer 15

1. Karyolysis: Fading basophilia of chromatin due to enzymatic degradation of DNA.
2. Pyknosis: Nuclear shrinkage and increased basophilia with condensed chromatin forming a dense, shrunken mass.
3. Karyorrhexis: Fragmentation of the pyknotic nucleus. Over 1 or 2 days, the nucleus in the necrotic cell may totally disappear.

Question 16

What is coagulative necrosis and how does it preserve the architecture of dead tissue?

Answer 16

Coagulative necrosis is a form of necrosis where the architecture of dead tissue is preserved for some days due to the denaturation of structural proteins and enzymes, which blocks the proteolysis of dead cells. The affected tissue has a firm texture.

Question 17

What characterizes liquefactive necrosis and where is it commonly seen?

Answer 17

Liquefactive necrosis is characterized by digestion of dead cells, transforming the tissue into a viscous liquid. It is commonly seen in focal bacterial or fungal infections and hypoxic death of cells within the central nervous system. The necrotic material often appears as pus.

Question 18

What is gangrenous necrosis and what are its two types?

Answer 18

Gangrenous necrosis refers to the necrosis of a limb, usually the lower leg, that has lost its blood supply. It typically involves coagulative necrosis. When bacterial infection is superimposed, it results in liquefactive necrosis, known as wet gangrene.

Question 19

What is caseous necrosis and what is its characteristic appearance?

Answer 19

Caseous necrosis is most often seen in tuberculous infections and is characterized by a friable white (cheeselike) appearance. Microscopically, it appears as a collection of fragmented or lysed cells and amorphous granular debris within a distinctive inflammatory border, forming a granuloma.

Question 20

Describe fat necrosis and how it is identified?

Answer 20

Fat necrosis refers to focal areas of fat destruction, often due to the release of activated pancreatic lipases in acute pancreatitis. This leads to fat saponification, forming chalky-white areas. Histologically, it shows shadowy outlines of necrotic fat cells, basophilic calcium deposits, and an inflammatory reaction.

Question 21

What is fibrinoid necrosis and in what conditions is it typically seen?

Answer 21

Fibrinoid necrosis is a form of vascular damage seen in immune reactions involving blood vessels. It occurs when antigen-antibody complexes are deposited in arterial walls, leading to a bright pink, fibrin-like appearance in H&E stains. It is seen in immunologically mediated vasculitis syndromes.

Question 22

How does apoptosis contribute to development?

Answer 22

During development, apoptosis removes supernumerary cells, aiding in the involution of primordial structures and the remodeling of maturing tissues. This process is essential for proper morphogenesis.

Question 23

What role does apoptosis play in hormone-dependent tissue involution?

Answer 23

Apoptosis is involved in the involution of hormone-dependent tissues upon hormone withdrawal. Examples include endometrial cell breakdown during the menstrual cycle, ovarian follicular atresia during menopause, and regression of the lactating breast after weaning.

Question 24

Why is apoptosis crucial for cell turnover in proliferating cell populations?

Answer 24

Apoptosis regulates cell turnover in proliferating cell populations, such as immature lymphocytes in the bone marrow and thymus, B lymphocytes in germinal centers, and epithelial cells in intestinal crypts, to maintain homeostasis.

Question 25

How does apoptosis prevent autoimmunity?

Answer 25

Apoptosis eliminates potentially harmful self-reactive lymphocytes during immune system development, preventing immune reactions against the body’s own tissues.

Question 26

What role does apoptosis play in response to DNA damage?

Answer 26

Apoptosis is triggered by DNA damage from radiation and cytotoxic anticancer drugs. If repair mechanisms fail to correct the damage, intrinsic mechanisms induce apoptosis to prevent the survival of cells with DNA mutations that could lead to malignant transformation.

Question 27

How does the accumulation of misfolded proteins lead to apoptosis?

Answer 27

The accumulation of misfolded proteins triggers the endoplasmic reticulum (ER) stress response, leading to apoptosis. This process prevents the potential toxic effects of improperly folded proteins on the cell.

Question 28

Describe the role of apoptosis in viral infections.

Answer 28

Apoptosis can be induced during viral infections by the virus itself (e.g., adenovirus, HIV) or by the host immune response. Cytotoxic T lymphocytes (CTLs) specific for viral proteins induce apoptosis of infected cells to eliminate reservoirs of infection, which can cause significant tissue damage.