Why metaplasia is a double sword?

Metaplasia is a double-edged sword because in respiratory tract respiratory epithelium is changed into squamous epithelium to protect against noxious stimulant but lost its ability mucus secretion and cilliary action which is important for protection against infection.
Moreover, the influences that predispose to metaplasia, if persistent, can initiate malignant transformation in metaplastic epithelium.

What is metaplasia? Short note.

Defenition:

Metaplasia is a reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type.

Mechanism of metaplasia:

Metaplasia does not result from a change in the phenotype of an already differentiated cell type; instead it is the result of a reprogramming of stem cells that are known to exist in normal tissues, or of undifferentiated
mesenchymal cells present in connective tissue. In a metaplastic change, these precursor cells differentiate
along a new pathway. The differentiation of stem cells to a particular lineage is brought about by signals generated by cytokines, growth factors, and extracellular matrix components in the cells’ environment.

Example:

1. Columnar to squamous: Occurs in the respiratory tract in response to chronic irritation. In the habitual cigarette smoker, the normal ciliated columnar epithelial cells of the trachea and bronchi are often replaced by stratified squamous epithelial cells.

2. Squamous to columnar: Occur, as in Barrett esophagus, in which the esophageal squamous epithelium is replaced by intestinal-like columnar cells under the influence of refluxed gastric acid.

3. Connective tissue metaplasia: The formation of cartilage, bone, or adipose tissue in tissues that normally do not contain these elements.

How hyperplasia differs from hypertrophy?

1. Hypertrophy is increase in the size of cell which result in increase in organ size. whereas hyperplasia is increase in number of cell due to a stimulus.
2. Hypertrophy is the result of increase production of cellular protein, in hyperplasia there is active cell division.
3. Hypertrophy can take place in any cell type whereas hyperplasia take place only in cells capable of division.

What is the clinical significance of pathological hyperplasia?

Pathologic hyperplasia constitutes a fertile soil in which cancerous proliferations may eventually arise. For example, patients with hyperplasia of the endometrium are at increased risk for developing endometrial cancer.

Describe the causes and clinical importance of hyperplasia.

Hyperplasia is of two types:

A. Physiologic hyperplasia

B. Pathologic hyperplasia.

Physiologic hyperplasia:

Physiologic hyperplasia due to the action of hormones or growth factors occurs in several circumstances: when there is a need to increase functional capacity of hormone sensitive organs; when there is need for compensatory increase after damage or resection.

So physiologic hyperplasia may be

• Hormonal: proliferation of the glandular epithelium of the female breast at puberty and during pregnancy.
• Compensatory: Liver regeneration after donation of a lobe of liver.

Pathologic hyperplasia:

Most forms of pathologic hyperplasia are caused by excessive or inappropriate actions of hormones or growth factors acting on target cells.

1. Endometrial hyperplasia
2. Benign prostatic hyperplasia
3. Hyperplasia is a characteristic response to certain viral infections, such as papillomaviruses, which cause skin warts and several mucosal lesions composed of masses of hyperplastic epithelium.

What is hyperplasia?

Definition:

Hyperplasia is defined as an increase in the number of cells in an organ or tissue in response to a stimulus.

What are the types of cellular adaptation?

Adaptations are reversible changes in the size, number, phenotype, metabolic activity, or functions of cells in response to changes in their environment.
Cellular adaptation is mainly of four types:

1. Hypertrophy: Hypertrophy refers to an increase in the size of cells, that results in an increase in the size of the affected organ.
2. Hyperplasia: Hyperplasia is defined as an increase in the number of cells in an organ or tissue in response to a stimulus.
3. Atrophy: Atrophy is defined as a reduction in the size of an organ or tissue due to a decrease in cell size and number.
4. Metaplasia: Metaplasia is a reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type.

What is diffenece bteween Necrosis and Apoptosis

Give pathogenesis of Apoptosis.

Apoptosis result from the activation of enzymes called caspases. Like many proteases, casepases exist as inactive proenzymes or zymogens and must undergo enzymatic cleavage to become active.
The process of apoptosis may be divided into an Initiation phase during which some caspases become catalytically active and an execution phase during which other caspases trigger the degradation of critical cellular components. The activation of caspases depends on a finely tuned balance between production of pro-apoptotic and anti-apoptotic proteins.
Two distinct pathways converge on caspase activation:
A. The mitochondrial pathway
B. The death receptor pathway

The mitochondrial pathway or the intrinsic pathway is the major mechanism of apoptosis in all mammalian cells. It results from increased permeability of the mitochondrial outer membrane with consequent release of death inducing.

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