Cellular Adaptation PDF

Cellular Adaptation Dr. Phyu Synn Oo Senior Lecturer Pathology & Pharmacology Department SOM, IMU Universiy [email protected] Pathology Team Dr Arun (AD) Prof Dr Puru AP Dr Sunil AP Dr Thin...

Cellular Adaptation Dr. Phyu Synn Oo Senior Lecturer Pathology & Pharmacology Department SOM, IMU Universiy [email protected] Pathology Team Dr Arun (AD) Prof Dr Puru AP Dr Sunil AP Dr Thin (HOD) Dr Saint (Sem 1 C) Dr Phyu Dr Sameera Dr Tehmina Dr Dhanashri Introduction to Pathology Understanding the causes of disease and the changes in cells, tissues, and organs associated with disease development. Pathology provides the scientific foundation for the practice of medicine.  Steps in the development of disease PSO, 2024 4 1. Etiology Origin of disease (underlying causes and modifying factors) Inherited genetic susceptibility and various environmental triggers 2. Pathogenesis Steps in the development of disease, from the initial etiologic trigger to the cellular and molecular changes  functional and structural abnormalities Lecture outcomes To list and classify the cellular adaptation to stress To describe the mechanism of cellular adaptation To demonstrate the causes of cellular adapatation PSO, 2024 6 Stages of the cellular response to stress and injurious stimuli PSO, 2024 7 Stages of the cellular response to stress and injurious stimuli PSO, 2024 8 Cellular adaptations  Reversible changes in number, size, phenotype, metabolic activity or functions – in response to changes in their environment.  Physiologic or pathologic adaptations 1) Hypertrophy 2) Hyperplasia 3) Atrophy 4) Metaplasia 5) Dystrophy - Degeneration of tissue or organ 6) Anaplasia - Loss of mature cellular differentiation, Malignant transformation 7) Dysplasia - Not regarded as a true adaptive response PSO, 2024 9 Proliferative capacities of cell types Based on their capacities to divide 1. Labile cells – continuously dividing as part of their normal homeostatic function E.g. keratinocytes, intestinal epithelial cells 2. Stable cells – do not usually divide under homeostatic condition but can do after injury/stimuli E.g. hepatocytes, renal tubular epithelial cells 3. Permanent cell – unable to divide after an injury E.g. neurons, cardiac myocytes PSO, 2024 10 Hypertrophy Enlargement of cells  results in an increase in the size of the organ No new cells, just larger cells. Due to the synthesis and assembly of additional intracellular structural components (proteins & organelles) Pure hypertrophy -> Cell types with a limited capacity to divide** PSO, 2024 11 Physiological hypertrophy - Uterus during pregnancy due to estrogen-stimulated smooth muscle hypertrophy and hyperplasia - Skeletal muscle and heart (cardiac muscle) due to increased workload A B C Normal uterus Gravid uterus PSO, 2024 B and C, Same magnification 12 Pathological hypertrophy Hypertrophy of the heart occurs with hypertension Myocardial fibers hypertrophy PSO, 2024 13 Mechanism of cardiac hypertrophy Release of growth factors and adrenergic hormones - Synthesis of more myofilaments per cells - Expression of genes - Switch of contractile that encode cellular protein from adult to proteins foetal forms (α- myosin heavy chain is -- replaced by the β form.) Ref: Kohli, Shrey & Ahuja, Suchit & Rani, Vibha. (2011). Transcription Factors in Heart: Promising Therapeutic Targets in Cardiac Hypertrophy. Current cardiology reviews.PSO, 7. 262-71. 2024 14 Hyperplasia Increase in the number of cells in an organ – proliferation of differentiated cells or progenitor cells Tissue contains cell populations capable of replication PSO, 2024 15  1) Hormonal hyperplasia Proliferation of glandular epithelium of the female breast at puberty and during pregnancy 2) Compensatory hyperplasia – residual tissue grows after removal or loss of part of an organ After partial Hepatectomy (liver resection), mitotic activity in the remaining hepatocytes begins as early as 12 hours later, eventually restoring the liver to its normal weight Ref: Rodimova S, et al. Effect of Hepatic Pathology on Liver Regeneration: The Main Metabolic Mechanisms Causing Impaired Hepatic Regeneration. International Journal of Molecular Sciences. 2023; 24(11):9112. https://doi.org/10.3390/ijms24119112 PSO, 2024 16 3) Hormonal imbalance  pathological hyperplasia Increased estrogenic stimulation  endometrial hyperplasia Androgen and oestrogen stimulation  benign prostatic hyperplasia Pathologic hyperplasia constitutes a fertile soil in which cancers may eventually arise. Ref: Webpath.med.utah.edu PSO, 2024 17 Which cellular change is most likely seen in the breast during pregnancy? ⓘ Start presenting to display the poll results on this slide. PSO, 2024 18  Hypertrophy vs Hyperplasia Hypertrophy Hyperplasia Definition Increased in the size of the tissue or Increase in the size/mass of the organ or organ due to increase in size of cells tissue due to increase in the number of cells Size of involved organs   Cells Number No change  Size  No change Organelles  No change Rate of cell division -  Synthesis of DNA, RNA &   protein PSO, 2024 19 Atrophy Reduced size of an organ or tissue caused by reduction in the size and number of cells Causes Decreased workload (e.g., Immobilization of a limb to permit healing of a fracture) Loss of innervation, Diminished blood supply Inadequate nutrition Loss of endocrine stimulation Aging (senile atrophy) The loss of hormone stimulation in menopause  Physiological change Over time, as atrophy worsens, affected cells may pass a threshold and undergo apoptosis. PSO, 2024 20 Atrophy - Mechanism A combination of decreased protein synthesis and increased protein degradation 1. Protein synthesis decreases because of reduced metabolic activity. 2. The degradation of cellular proteins occurs mainly by the ubiquitin- proteasome pathway. Nutrient deficiency and disuse  activates ubiquitin ligases  target the cellular proteins  for degradation in the proteasome. PSO, 2024 21 3. Increased autophagy Autophagy is the process in which the starved cell eats its own organelles in an attempt to survive. PSO, 2024 22 Testicular atrophy Left – normal testis Right–atrophic testis PSO, 2024 23  Atrophy of the brain (A) Normal brain of a young adult. (B) Atrophy of the brain in an 81-year-old man with atherosclerotic cerebrovascular disease. Atrophy of the brain is due to aging and reduced blood supply. Note that loss of brain substance narrows the gyri and widens the sulci. PSO, 2024 24 Metaplasia Metaplasia is a change in which one adult cell type is replaced by another adult cell type. A cell type sensitive to a particular stress is replaced by another cell type better able to withstand the adverse environment. Reprogramming of stem cells to differentiate along a new pathway Malignant transformation (+) PSO, 2024 25 Metaplasia vs transdifferentiation (2011 & 2017, Nature Review) Transdifferentiation PSO, 2024 26 PSO, 2024 27 Metaplasia of normal columnar (left) to squamous epithelium (right) in a bronchus, shown schematically (A) and histologically (B). PSO, 2024 28 PSO, 2024 29  Normal Columnar/ squamous intestinal metaplasia epithelium PSO, 2024 30 Differences among atrophy, hypertrophy and hyperplasia Atrophy Hypertrophy Hyperplasia Definition Reduced size of organ or Increased in the size of the Increase in the size/mass of tissue resulting from a tissue or organ due to the organ or tissue due to decreased in cell size and increase in size of cells increase in the number of number cells Size of involved organs    Cells Number  No change  Size   No change Organelles   No change Rate of cell division - -  Synthesis of DNA, RNA -   & protein PSO, 2024 31 A 45-year-old woman is investigated for hypertension and is found to have smaller right kidney. Contrast studies reveals stenosis of the right artery. Which adaptive change occurs in her kidney? ⓘ Start presenting to display the poll results on this slide. PSO, 2024 32 References Kumar V, Abbas AK, Aster JC, Deyrup AT, Das A (2023). ‘Chapter 1: Cell Injury, Cell Death and Adaptations,’ in Robbins & Kumar Basic Pathology, 11th ed. Philadelphia, Pennsylvania: Elsevier. Kumar V, Abbas AK, Aster JC. (2018). ‘Chapter 2: Cell Injury, Cell Death, and Adaptations,’ in Robbins Basic Pathology, 10th ed., Philadelphia, Pennsylvania: Elsevier. Pp.31-56. https://next.amboss.com/us/article/VP0GdT?q=cell%20death#Zb3483fa4a700b90a3cd8ccb27fb6b899 PSO, 2024 33  THANK YOU PSO, 2024 34