What do you mean by Apoptosis? What are the causes of Apoptosis?

Apoptosis:

Apoptosis is a pathway of cell death that is induced by a tightly regulated suicide program in which cells
destined to die activate intrinsic enzymes that degrade the cells’ own nuclear DNA and nuclear and cytoplasmic proteins.

Causes of Apoptosis:

Apoptosis occurs normally both during development and throughout adulthood, and serves to remove unwanted, aged, or potentially harmful cells. It is also a pathologic event when diseased cells become damaged beyond repair and are eliminated.

Apoptosis in Physiologic Situations:

• The destruction of cells during embryogenesis, including implantation, organogenesis, developmental involution, and metamorphosis.
• Involution of hormone-dependent tissues upon hormone withdrawal, such as endometrial cell breakdown during the menstrual cycle, ovarian follicular atresia in menopause, the regression of the lactating breast after weaning, and prostatic atrophy after castration.
• Cell loss in proliferating cell populations, such as immature lymphocytes in the bone marrow and thymus and B lymphocytes in germinal centers that fail to express useful antigen receptors.
• Elimination of potentially harmful self-reactive lymphocytes, either before or after they have completed their maturation, so as to prevent reactions against one’s own tissues.
• Death of host cells that have served their useful purpose, such as neutrophils in an acute inflammatory response, and lymphocytes at the end of an immune response.

Apoptosis in Pathologic Conditions:

• DNA damage. Radiation, cytotoxic anticancer drugs, and hypoxia can damage DNA, either directly or via production of free radicals.
• Accumulation of misfolded proteins.
• Cell death in certain infections, particularly viral infections, in which loss of infected cells is largely due to apoptosis that may be induced by the virus (as in adenovirus and HIV infections) or by the host immune response (as in viral hepatitis).
• Pathologic atrophy in parenchymal organs after duct obstruction, such as occurs in the pancreas, parotid gland, and kidney.

Why does fat necrosis occur in acute pancreatitis?

Fat necrosis is a term that is entrenched in medical practice but does not in reality denote a specific pattern of necrosis. Rather, it refers to focal areas of fat destruction, typically resulting from release of activated pancreatic lipases into the substance of the pancreas and peritoneal cavity. This occurs in acute pancreatitis where pancreatic enzymes leak out of acinar cells and liquefy the membranes of fat cells in the perotoneum. The released lipases split the triglyceride esters contained within fat cells. The fally acids, so derived, combine with calcium to produce grossly visible chalky white areas, which enable the surgeon and the pathologist to identify the lesions.

Define Necrosis. Classify Necrosis.

Necrosis:
The morphologic appearance of necrosis as well as necroptosis is the result of denaturation of intracellular proteins and enzymatic digestion of the lethally injured cell. The enzymes that digest the necrotic cell are derived from the lysosomes of the dying cells themselves and from the lysosomes of leukocytes that are called in as part of the inflammatory reaction.

Classification of necrosis:
1. Coagulative necrosis is a form of necrosis in which the architecture of dead tissues is preserved for a span of at least some days. Ischemia caused by obstruction in a vessel may lead to coagulative necrosis of the supplied tissue in all organs except the brain. A localized area of coagulative necrosis is called an infarct.

2. Liquefactive necrosis: in contrast to coagulative necrosis, is characterized by digestion of the dead cells, resulting in transformation of the tissue into a liquid viscous mass. It is seen in focal bacterial or occasionally fungul infections. The necrotic material is frequently creamy yellow because of the pressence of dead leukocytes and is called pus.

3. Gangrenous necrosis: is not a specific pattern of cell death but the term is commonly used in clinical practice. It is usually applied to a limb, generally the lower leg, that has undergone necrosis involving multiple tissue planes.

4. Caseous necrosis: is encountered most often infoci of tuberculous infection. The term caseous is derived from the febrile white appearance of the area of necrosis.

5. Fat necrosis: is a term that is entrenched in medical parlance but does not in reality denote a specific pattern of necrosis.

6. Fibrinoid necrosis: is a special form of necrosis usually seen in immune reactions involving blood vessels. This pattern of necrosis typically occurs when complexes of antigens and antibodies are deposited in the walls of arteries. 

How free radicals are initiated? What are their effects on cells?

How free radicals are produced:

Free radicals are chemicals species that have a single unpaired electron in an outer orbit. Unpaired electrons are highly reactive and attack and modify adjacent molecules, such as inorganic or organic chemiclas proteins, lipids, carbohydrate, nucleic acids many of which are key components of cell membranes and nuclei.

Free radicals may be generated within cells in severals ways:
1. The reduction oxidation reactions that occur during normal metabolic processes.
2. Absorption of radiant ebergy(e.g. ultraviolet light, x-rays)
3. Rapid bursts of free radicals are produced in activated leukocytes during inflammation.
4. Enzymatic metabolism of exogenous chemicals or drugs can generate free radicals that are not reactive oxygen specices but have similar effects.
5. Transition metals such as iron and copper donate or accept free electrons during intracellular reactions and catalyze free radical formation.
6. Nitric oxide an important chemical mediator generated by endothelial cells, macrophages, neurons and other cell types.

Effects of free radicals:
1. Lipid peroxidation in membranes.
2.Oxidative modification of proteins
3. Lesions in DNA