Necrosis and Apoptosis

Necrosis and Apoptosis

Necrosis is an abnormal process of cell death that causes inflammation and affects tissue function.

Morphological patterns of necrosis:

• Coagulative necrosis:

• Due to lack of oxygen, the cells become cloudy white, persist for a short time and then turn into liquefactive necrosis due to heterolysis.

• Cause: Intracellular acidosis.

• Occurs in: Myocardial infarction, kidney.

• Liquefactive necrosis:

• Cells are soft, pale, and liquefied in the middle, surrounded by inflammatory cells.

• Mechanism: Due to the strong activity of lysosomal enzymes.

• Occurs in: Hypoxic brain injury (cerebral softening), bacterial suppurative inflammation (abscess).

• Gangrenous necrosis:

• Necrosis of the limb due to lack of blood supply.

• Two forms:

• Dry gangrene (coagulative necrosis).

• Wet gangrene (liquefactive necrosis).

• Fat necrosis:

• Occurs in acute pancreatitis.

• Fat cells are destroyed, lose boundaries, have calcium deposition and infiltration of inflammatory cells.

• Caseous necrosis:

• Occurs in tuberculosis.

• Tissue is completely destroyed, replaced by granules which are fragments of necrotic cells.

Apoptosis is a programmed process of cell death that occurs in an orderly manner, does not cause inflammation and does not affect tissue function.

Two types of apoptosis:

• Physiological apoptosis:

• Occurs during embryonic development, tissue renewal (intestinal epithelium, lymphocyte cells in bone marrow), regression of hormone-dependent tissues (endometrium), reduction in the number of harmful leukocytes.

• Pathological apoptosis:

• Due to DNA damage, accumulation of misfolded proteins, infection (especially viral infection).

Apoptotic pathways:

• Intrinsic (Mitochondrial):

• Starts from the mitochondria, releases factors that promote apoptosis.

• Extrinsic (Death receptor):

• Due to the action of external signals such as TNF, FASL, activating the caspase enzyme chain that cleaves the nucleus.

Proteins involved in apoptosis:

• Apoptosis-promoting proteins: Bax, Bak, Bad, Bim, Bik, Nox, Puma, Noxa.

• Apoptosis-inhibiting proteins: Bcl-2, Bcl-xL, Bcl-X, A1, Ku70, Mcl-1.

Hypertrophy is an increase in the size of cells, leading to an increase in the size of tissues and organs.

Occurs in:

• Physiological: Partial hepatectomy, hematopoietic stem cells in high altitude.

• Pathological: Cervical smooth muscle in pregnancy, heart muscle in hypertension, aortic stenosis, skeletal muscle of athletes.

Hyperplasia is an increase in the number of cells, leading to an increase in the size of tissues and organs.

Occurs in:

• Physiological: Partial hepatectomy, hematopoietic stem cells in high altitude.

• Pathological: Endometrial glands during the menstrual cycle due to the action of estrogen, nodular goiter, multinodular goiter, prostatic tissue causing urethral obstruction.

Atrophy is a decrease in the size of cells, leading to a decrease in the size of tissues and organs.

Degeneration is a decrease in the number of cells, leading to a decrease in the size of tissues and organs.

Atrophy and degeneration are two different processes:

• Incorrect to claim that atrophy and degeneration are the same.

Combination of atrophy and degeneration:

• Occurs in the cervical endometrium and cervical epithelium in postmenopausal women.

Intracellular accumulation is the abnormal accumulation of substances within cells.

Substances commonly accumulated intracellularly:

• Water:

• Two types: Cellular swelling and hydropic degeneration.

• Occurs in liver cells.

• Lipids:

• Triglyceride: Occurs in liver cells of alcoholics.

• Use cryostat section + Oil red O staining (because xyclen staining will cause discoloration of triglycerides).

• Glucids:

• Occurs in renal tubules in diabetic patients.

• PAS staining.

• Proteins:

• Due to 3 mechanisms:

• Excessive uptake in renal tubular cells in nephrotic syndrome. Forms hyaline bodies.

• Inability to excrete in multiple myeloma.

• Damage to the cell cytoskeleton in liver cells due to alcohol. Proteins are denatured and precipitated by alcohol. This is called Mallory bodies.

Pigment accumulation:

• Exogenous: Carbon dust in the hilar lymph nodes, alveoli, tattoo ink.

• Endogenous:

• Lipofuscin (wear-and-tear pigment): Occurs in the heart, liver. Fontana staining: black.

• Hemosiderin: Occurs in hematomas, spleen. Perls staining: blue.

• Bilirubin: Occurs in bile duct obstruction. Fouchet staining: green.

• Melanin: Occurs in melanoma (malignant tumor originating from melanocytes).

Extracellular deposition is the abnormal accumulation of substances outside cells.

Substances commonly deposited extracellularly:

• Cholesterol

• Proteins: Hyalin, fibrin and amyloid (orange color stained red congo, lemon yellow under polarized light).

• Calcium: Dystrophic calcification and metastatic calcification.

• Urate

Extracellular deposition: Calcium:

• Dystrophic calcification: Occurs in hematomas, papillary tumors, mammary glands.

• Metastatic calcification: Manifests as hypercalcemia, deposition in renal calices, ureters.

Thyroid gland:

• Thyroid gland has two types of cells:

• Follicular thyroid cells: Form papillary tumors.

• Medullary thyroid cells: Form medullary thyroid carcinoma.

Cell necrosis:

• Necrosis of pancreatic islet cells

• Necrosis of liver cells

• Necrosis of renal tubular cells

Causes of cell necrosis:

• Lack of oxygen: Due to physical, chemical, infectious, abnormal immune response.

Apoptosis occurs in:

• Intestinal epithelium, lymph nodes

• Glandular epithelium in mammary ducts ceases milk production

Note: This text is a general overview of necrosis and apoptosis. For a better understanding, please refer to other professional materials.