Cellular Adaptive Responses PDF

Cellular Adaptive Response Pmed-Pdent-Pphrm Pathology Team By the end of this session students should be able to: ◦ Recognize how cell can adapt after exposure to injury or stress Session’s Objectives ◦ Identify different types of cellular adaptations (atrophy, hypertrophy, hyperplasia & metaplasia)...

Cellular Adaptive Response Pmed-Pdent-Pphrm Pathology Team By the end of this session students should be able to: ◦ Recognize how cell can adapt after exposure to injury or stress Session’s Objectives ◦ Identify different types of cellular adaptations (atrophy, hypertrophy, hyperplasia & metaplasia) ◦ Provide definition, mechanism and examples of each type ◦ Recognize intracellular accumulations Pathology ◦ It is the bridge between clinical practice and basic science. (Pathology makes the basis of Medicine) ◦ Study of: ◦ Underlying causes of diseases (etiology) ◦ Mechanisms of diseases (pathogenesis) ◦ Changes in cells, tissue, and organs: Structural (morphology) , biochemical and functional (clinical signs and symptoms, and outcome). ◦ Molecular basis of diseases. ◦ General and systemic pathology. The Cell and the Environment ◦ Adaptive Responses: ◦ When cells exposed to physiological stresses or pathological stimuli, they undergo adaptations to achieve a new steady state to preserve viability and function ◦ Types of cellular adaptation: ◦ Atrophy ◦ Hypertrophy ◦ Hyperplasia ◦ Metaplasia Effects of stresses on cells Stresses affect normal cell functions Continuous stress and ineffective adaptation Cell Injury Adaptive changes 1. 2. 3. 4. Atrophy Hypertrophy Hyperplasia Metaplasia Reversible cell Injury Irreversible cell Injury Apoptosis Necrosis Cellular Adaptation to Stress ◦ Cellular adaptations are mechanisms to cope with the new situation or injurious stimulus ◦ Reversible changes in number, size, appearance, metabolic activity or functions of cells in response to changes in the environment ◦ Physiological adaptation ◦ Cell response to normal physiological stimuli, e.g. hormones or chemical mediators ◦ Pathological adaptation ◦ Cell response to abnormal or pathological stimuli to escape injury Cellular Adaptations to Injury or stress Allows tissue to survive or maintain normal function ◦ Four cellular Adaptations to Injury or stress: ◦ Atrophy ◦ Hypertrophy ◦ Hyperplasia ◦ Metaplasia Cellular Responses to Injury Nature of injurious stimuli: Cellular response: (Altered physiologic stimuli; some nonlethal injurious stimuli) Increased demand, increased stimulation (e.g.; growth factors, hormones) Decreased nutrients, decreased stimulation Chronic irritation (physical or chemical) (Cellular adaptations) Hyperplasia, hypertrophy, Atrophy metaplasia Hypertrophy Increase in cell size resulting in increase in size of the organ “No new cells, just bigger cells” Seen in both dividing & non-dividing cells “No cell swelling, but more structural components” Causes of Hypertrophy ◦ Physiological Hypertrophy: ◦ Pathological hypertrophy: ◦ Growth of the uterus during pregnancy. ◦ Myocardial hypertrophy in hypertension ◦ Hypertrophy of breasts during lactation. ◦ Hypertrophic cardiomyopathy ◦ Skeletal muscular enlargement in athletes due to increase work load ◦ Compensatory Hypertrophy due to loss of paired organ e.g. kidney Physiologic hypertrophy of uterus during pregnancy Gross appearance of a normal uterus (right) and a gravid uterus (left). ◦ Robbins Pathology 10th edition Pathological Hypertrophy of heart Left Ventricular hypertrophy Due to Hypertension Biochemical Mechanisms of cardiac hypertrophy Hyperplasia Increase in cell numbers with increase in organ size. Hyperplasia and hypertrophy frequently occur together in response to same stimuli. Hyperplasia can occur in cells with replicative capacity and does not occur in non-dividing cells e.g. nerves and muscles (skeletal and cardiac) ◦ Physiological hyperplasia ◦ Increase in functional demand of an organ e.g. Causes of Hyperplasia ◦ 1. Hormonal stimulation: ◦ proliferation of glandular epithelium in female breast at puberty, pregnancy and lactation ◦ physiologic hyperplasia in pregnant uterus. ◦ 2. Compensatory: ◦ Residual tissue grows after removal or loss of part of organ e.g. hyperplasia occur when part of liver is resected and in wound healing ◦ Pathological hyperplasia ◦ occur in response of high hormone levels e.g. Causes of Hyperplasia ◦ Endometrial hyperplasia: relative or absolute estrogen excess. ◦ Benign prostatic hyperplasia: excess androgens level Benign Prostatic Hyperplasia Benign Prostatic Hyperplasia ◦ Cellular proliferation is promoted by (any or all of): Mechanism of Pathologic Hyperplasia ◦ Production of more growth factors ◦ Increased levels of growth factor receptors ◦ Activation of particular intracellular signaling pathways ◦ stem cells  development of new cells Atrophy Decrease or shrinkage in cell size by loss of cell organelles and decrease in cell number leading to reduction in size of tissue or organ Physiologic Atrophy: During early development embryonic structures, notocord or thyroglossal duct, undergo atrophy during fetal development. Causes of Atrophy Loss of hormonal stimulation in menopause (Post menopause endometrium) Causes of Atrophy Pathological atrophy: Decrease in workload/ use of organ (disuse atrophy e.g. fracture). Prolong pressure (pressure atrophy e.g. benign tumor causing atrophy of surrounding tissue by pressure) Reduced blood supply (brain atrophy due to long standing ischemia) Lack of nutrition (e.g Marasmus) Lack of nervous stimulation (denervation atrophy of skeletal muscles) Aging (senile atrophy) Increase protein degradation and decrease protein synthesis in cells leads to decrease metabolic activity Increased protein degradation by: Atrophy Pathogenesis Lysosomal enzymes Autophagy (digestion of the cell’s own components) Ubiquitin – proteasome pathway MECHANISM OF ATROPHY Protein degradation occurs by ubiquitin proteasome pathway Ubiquitin ligases  attach ubiquitin to proteins  cause degradation in proteasomes Glucocorticoids Thyroid hormone TNF + Ubiquitin-proteasome pathway - Insulin Brain Atrophy Metaplasia A reversible replacement of one mature (differentiated/ adult) cell type by another mature cell type If persistent, can lead to malignant transformation in metaplastic epithelium. Metaplasia from columnar to squamous epithelium: (Most common) Epithelial Metaplasia As occurs in the respiratory tract in response to chronic irritation, in smokers. Stones in the excretory ducts of the salivary glands, pancreas, or bile ducts Uterine cervical metaplasia during reproductive age. Vitamin A deficiency induces squamous metaplasia in respiratory epithelium. Columnar to Squamous Metaplasia Robbins Pathology 10th edition ◦ Metaplasia from squamous to columnar: Epithelial Metaplasia ◦ As in Barrett’s oesophagus, in which the squamous esophageal epithelium is replaced by intestinal-like columnar cells ◦ Can lead to oesophageal cancer ◦ Reprogramming & differentiation of stem cells or of undifferentiated mesenchymal cells along a new pathway Mechanism of Metaplasia ◦ By signals generated by ◦ Cytokines ◦ Growth factors ◦ Extracellular matrix components Signals cause  expression of tissue-specific & differentiation genes which determine the pathway of differentiation ◦ Intracellular accumulation of abnormal amounts of various substances, this may be harmless or may cause cell injury. ◦ substances fall into three categories: Intracellular Accumulations (1) A normal cellular constituent accumulated in excess (water, lipid, protein, and carbohydrates). (2) An abnormal substance, either exogenous (a mineral or products of infectious agents), or endogenous (a product of abnormal synthesis or metabolism). (3) A pigment: exogenous (carbon) and endogenous (Lipofuscin: wear and tear pigment and Hemosiderin) Summary