calcification, cellularaging.pptx slides presentation

Calcification is a natural process that occurs in the body, where calcium salts deposit in tissues, leading to hardening and stiffening. While calcification is essential for maintaining strong bones and teeth, abnormal calcification can occur in various tissues, including muscles, joints, and organs. This can lead to a range of health problems, including arthritis, kidney stones, and cardiovascular disease.

At the cellular level, calcification is closely linked to the process of aging. As we age, our cells undergo a range of changes, including DNA damage, telomere shortening, and epigenetic alterations. These changes can lead to cellular senescence, where cells become dysfunctional and contribute to the aging process.

One of the key drivers of cellular aging is oxidative stress, which occurs when the body's antioxidant defenses are overwhelmed by free radicals. Free radicals are highly reactive molecules that can damage cellular components, including DNA, proteins, and lipids. As we age, our cells become less able to cope with oxidative stress, leading to the accumulation of cellular damage.

Calcification can also contribute to cellular aging by disrupting normal cellular function. For example, the deposition of calcium salts in muscles can lead to muscle stiffness and weakness, while the calcification of joints can cause arthritis and mobility problems.

In addition to its role in cellular aging, calcification is also closely linked to the process of inflammation. Chronic inflammation is a hallmark of many age-related diseases, including cardiovascular disease, diabetes, and cancer. Calcification can contribute to inflammation by activating immune cells and promoting the release of pro-inflammatory cytokines.

At the molecular level, calcification is regulated by a complex interplay of signaling pathways and molecular mechanisms. One of the key regulators of calcification is the Wnt/β-catenin signaling pathway, which plays a critical role in bone development and homeostasis. Abnormal activation of this pathway has been implicated in a range of diseases, including osteoporosis, arthritis, and cancer.

Another key regulator of calcification is the vitamin D receptor (VDR), which plays a critical role in maintaining calcium homeostasis and bone health. Abnormalities in VDR signaling have been implicated in a range of diseases, including osteomalacia, rickets, and kidney disease.

In recent years, there has been growing interest in the role of epigenetic mechanisms in regulating calcification and cellular aging. Epigenetic mechanisms, such as DNA methylation and histone modification, play a critical role in regulating gene expression and cellular function. Abnormalities in epigenetic mechanisms have been implicated in a range of diseases, including cancer, cardiovascular disease, and neurodegenerative disorders.

In conclusion, calcification and cellular aging are closely linked processes that contribute to a range of age-related diseases.underd

1. Introduction to Pathology Prepared by: Rafia Ali

2. METAPLASIA It is a reversible change in which an adult cell type (epithelial or mesenchymal) is replaced by another adult cell type of the same tissue.

3. It may represent an adaptive substitution of cells more sensitive to stress by other cell types better able to withstand the adverse environment.

4. EXAMPLES a - uterine endocervical glandular epithelium due to chronic irritation b- transitional epithelium of urinary bladder, ureter or renal pelvis due to chronic irritation by bilharziasis or stones c- columnar epithelium of gall bladder due to chronic irritation by stones or inflammation d- pseudostratified ciliated columnar respiratory epithelium due to chronic irritation by habitual cigarette smoking or in vitamin A deficiency.

5. If the influences that induce metaplastic transformation of the epithelium are persistent, they may lead to cancer transformation in the metaplastic epithelium , e.g. squamous metaplasia of transitional epithelium of the urinary bladder by bilharziasis will lead to squamous cell carcinoma.

6. MESENCHYMAL CELL METAPLASIA: Myxomatous change of fibrous tissue. Transformation of fibroblasts to osteoblasts or chondroblasts to produce bone or cartilage in soft tissues in foci of injury. small spindle-shaped cells with large nuclei, prominent nucleoli and fine chromatin . These are multipotent stem cells that differentiate as progenitor cells for all types of connective tissue , 

7. HYPOPLASIA It is the decrease in size of an organ due to incomplete development in embryonic or fetal life e.g. kidney and uterus.

8. AGENESIS Complete absence of an organ or a part of an organ e.g. solitary kidney, in such case the other kidney is absent.

9. DYSPLASIA A term used to describe disorderly but non-neoplastic proliferation. It is a loss in the uniformity of individual cells as well as in their architectural orientation

10. Dysplastic changes reveal pleomorphism, hyperchromatism, abundant mitoses, and loss of normal orientation. Dysplastic changes are mostly seen in epithelial cells especially in the cervix uteri.

11. When dysplastic changes are mild they are often reversible by removal of the inciting cause (e.g. chronic irritation). On the other hand, when dysplastic changes are marked and involve the entire thickness of the epithelium, the lesion in this case is considered as pre-invasive neoplasm and is referred to as "carcinoma in situ".

12. .

13. CAUSES Oxygen deprivation (hypoxia) affects aerobic respiration and therefore ability to generate adenosine triphosphate (ATP). Ischemia (loss of blood supply) Inadequate oxygenation (e.g., cardiorespiratory failure) Loss of oxygen-carrying capacity of the blood (e.g., anemia, carbon monoxide poisoning)

14. Physical agents , including trauma, heat, cold, radiation, and electric shock Chemical agents and drugs, including therapeutic drugs, poisons, environmental pollutants, and “social stimuli” (alcohol and narcotics) Infectious agents , including viruses, bacteria, fungi, and parasites Immunologic reactions , including autoimmune diseases cell injury following responses to infection Genetic derangements , such as chromosomal alterations and specific gene mutations Nutritional imbalances , including protein–calorie deficiency or lack of specific vitamins, as well as nutritional excesses.

15. PATHOLOGIC CALCIFICATION Initiation (nucleation ) occurs extracellularly or intracellularly. Propagation of crystal formation depends on the concentration of calcium and phosphates, the presence of inhibitors, structural components of the extracellular matrix.

16. DYSTROPHIC CALCIFICATION

17. MORPHOLOGY OF DYSTROPHIC CALCIFICATION CALCIUM SALTS are grossly seen as fine white granules or clumps, often felt as gritty deposition Histologically calcification appears as intracellular and/or extracellular basophilic deposits in time heterotopic bone may be formed in the focus of calcification

18. MORPHOLOGY OF CALCIFIED SALTS Histologically, calcium salts are basophilic, amorphous granular. They can be intracellular, extracellular, or both. In the course of time, heterotopic( bone grows in tissues where it typically wouldn’t.) bone may be formed in the focus of calcification. Progressive deposition on outer layers may create lamellated configurations, called psammoma bodies ( papillary cancers).

19. METASTATIC CALCIFICATION • Elevated parathyroid hormone (e.g., hyperparathyroidism due to parathyroid tumors or ectopic parathyroid hormone secreted by other neoplasms) • Bone destruction , as in primary marrow malignancies (e.g., multiple myeloma) or by diffuse skeletal metastasis (e.g., breast cancer), by accelerated bone turnover (Paget’s disease), or immobilization • Vitamin D –related disorders, including vitamin D intoxication and systemic sarcoidosis • Renal failure , causing secondary hyperparathyroidism due to phosphate retention and the resulting hypocalcemia

20. MORPHOLOGY OF METASTATIC CALCIFICATIONS METSTATIC CALCIFICATION can occur widely throughout the body but principally affects the interstitial tissue of the vasculature, kidney, lungs and gastric mucosa Calcium deposition morphologically resembled those described in dystrophic calcification

21. CELLULAR AGING Cellular aging—reflecting the progressive accumulation of sublethal cellular and molecular damage due to both genetic and exogenous influences—leads to cell death and diminished capacity to respond to injury; it is a critical component of the aging of the entire organism

22. CONT.… Cellular senescence refers to the concept that cells have a limited capacity for replication. telomere shortening (i.e., incomplete replication of chromosome ends) Accumulated metabolic and genetic damage clearly contribute to cellular aging. Increased ROS production